Type I interferon response and vascular alteration in chilblain-like lesions during the COVID-19 outbreak.

BACKGROUND: The outbreak of chilblain-like lesions (CLL) during the COVID-19 pandemic has been reported extensively, potentially related to SARS-CoV-2 infection, yet its underlying pathophysiology is unclear. OBJECTIVES: To study skin and blood endothelial and immune system activation in CLL in comparison with healthy controls and seasonal chilblains (SC), defined as cold-induced sporadic chilblains occurring during 2015 and 2019 with exclusion of chilblain lupus. METHODS: This observational study was conducted during 9-16 April 2020 at Saint-Louis Hospital, Paris, France. All patients referred with CLL seen during this period of the COVID-19 pandemic were included in this study. We excluded patients with a history of chilblains or chilblain lupus. Fifty patients were included. RESULTS: Histological patterns were similar and transcriptomic signatures overlapped in both the CLL and SC groups, with type I interferon polarization and a cytotoxic-natural killer gene signature. CLL were characterized by higher IgA tissue deposition and more significant transcriptomic activation of complement and angiogenesis factors compared with SC. We observed in CLL a systemic immune response associated with IgA antineutrophil cytoplasmic antibodies in 73% of patients, and elevated type I interferon blood signature in comparison with healthy controls. Finally, using blood biomarkers related to endothelial dysfunction and activation, and to angiogenesis or endothelial progenitor cell mobilization, we confirmed endothelial dysfunction in CLL. CONCLUSIONS: Our findings support an activation loop in the skin in CLL associated with endothelial alteration and immune infiltration of cytotoxic and type I IFN-polarized cells leading to clinical manifestations.

Carotid webs associated with ischemic stroke. Updated general review and research directions.

Carotid web (CaW) is an intimal variant of fibromuscular dysplasia strongly associated with ipsilateral cerebral infarction. Although considered rare, it is a recent and increasing concern for physicians involved in stroke diagnosis and management. The present general review relies on a systematic literature analysis and aims to update readers on the latest knowledge in the field of symptomatic CaW (syCaW). CaW associated with ipsilateral cerebral infarction or transient ischemic attack has been identified in 189 patients. Ischemic strokes (IS) mostly occur in middle age (mean 46 years) and predominately in females (66%). The high frequency of African descendant patients among case reports and series (58%) suggests an ethnic susceptibility for CaW development. CaW features are characterised by a shelf-like intraluminal defect on contrast sagittal imaging, a linear defect that splits the lumen on axial section, a post-contrast stagnation rostral to the lesion and a frequent contralateral mirrored CaW (26.6%). An artery-to-artery embolism mechanism is widely accepted via CaW blood stasis, thrombus formation and clot fragmentation scattered by blood flow. Therefore, cerebral infarctions are often large related to a high proportion of proximal occlusion (62.5%). CaW confers a high rate of IS recurrence despite standard anti-platelet treatment that reaches 33.3% of patients prospectively followed with a median time to event of one year. Although no randomised therapeutic studies are available, surgery (n=39) or stenting (n=50) have been often proposed and seem to avoid recurrences. CaW clearly emerges as a cause of cryptogenic embolic stroke and should be systematically investigated in routine. A large number of points remain to be elucidated and CaW patients should be steadily included in registries and randomised therapeutic studies.

[Use of antiplatelet therapy and direct oral anticoagulants in candidates for renal transplantation: The French guidelines from the CTAFU]. / Recommandations françaises du Comité de transplantation de l'association française d'urologie (CTAFU) : agents antiplaquettaires et anticoagulants oraux directs en transplantation rénale.

OBJECTIVE: To define guidelines for the use of antiplatelet therapy (AT) and direct oral anticoagulants (DOAC) in candidates for kidney allotransplantation. METHOD: A review of the medical literature following a systematic approach was conducted by the CTAFU to report the use of AT and DOAC before major surgery and in the setting of advanced chronic kidney disease, defining their managment prior to kidney transplantation with the corresponding level of evidence. RESULTS: DOAC are not recommended in patients under dialysis. Aspirin therapy, but not anti-P2Y12 and DOAC, may be maintained during renal transplantation. Anti-P2Y12 and DOAC should not be use in patients awaiting a kidney transplant, except when a living donor is scheduled, therefore authorizing treatment interruption in optimal conditions. Further data regarding DOAC reversion and monitoring may improve their use in this setting. Global level of evidence is weak. CONCLUSION: These French recommendations should contribute to improve surgical management of kidney transplant candidates exposed to AT or DOA.

Specificities of acute phase stroke management in the elderly.

Health professionals are currently facing the challenge of managing an increasing number of old patients presenting with acute stroke, due to rapid aging of the population. Compared to their younger counterparts, elderly patients differ in many ways in the setting of acute stroke. Apart from a striking high stroke incidence, which increases exponentially as age increases, cardioembolism also becomes, as patients age, the main cause of ischemic stroke. Delirium, which can challenge the diagnosis, is frequent at the acute phase of stroke, and may be related to an underlying dementia, which is almost exclusively observed in the elderly during stroke. At all levels, management of elderly stroke patients is suboptimal, especially when they are cognitively impaired, with insufficiencies including admission to stroke units, applying standards of care and investigation, reperfusion therapy for ischemic stroke, and finally transfer to rehabilitation centers. A paradigm shift must take place to limit age-related discrimination for acute-phase management of stroke.

Angioedema associated with thrombolysis for ischemic stroke: analysis of a case-control study.

BACKGROUND: Bradykinin-mediated angioedema (AE) is a complication associated with thrombolysis for acute ischemic stroke. Risk factors are unknown and management is discussed. OBJECTIVES: To clarify risk factors associated with bradykinin-mediated AE after thrombolysis for acute ischemic stroke. METHODS: In a case-control study conducted at a French reference centre for bradykinin angiœdema, patients with thrombolysis for acute ischemic stroke and a diagnosis of bradykinin-mediated angiœdema, were compared to controls treated with thrombolysis treatment without angiœdema. RESULTS: Fifty-three thrombolysis-related AE were matched to 106 control subjects. The sites of attacks following thrombolysis for ischemic stroke mainly included tongue (34/53, 64%) and lips (26/53, 49%). The upper airways were involved in 37 (70%) cases. Three patients required mechanical ventilation. Patients with bradykinin-mediated angiœdema were more frequently women [33 (62%) vs. 44 (42%); P = 0.01], had higher frequency of prior ischemic stroke [12 (23%) vs. 9 (8%); P = 0.01], hypertension [46 (87%) vs. 70 (66%); P = 0.005], were more frequently treated with angiotensin-converting enzyme inhibitor [37 (70%) vs. 28 (26%); P < 0.001] and were more frequently hospitalized in intensive care medicine [ICU; 11 (21%) vs. 5 (5%); P = 0.004]. In multivariate analysis, factors associated with thrombolysis-related AE were female sex [odds ratio (OR), 3.04; 95% confident interval (CI), 1.32-7.01; P = 0.009] and treatment with angiotensin-converting enzyme inhibitors [(OR), 6.08; 95% (CI), 2.17-17.07; P < 0.001]. CONCLUSIONS: This case-control study points out angiotensin-converting enzyme inhibitors and female sex as risk factors of bradykinin AE associated with thrombolysis for ischemic stroke.

[Venous thromboembolism and urological cancer: Epidemiology and therapeutically management]. / Maladie thromboembolique veineuse et cancers urologiques : épidémiologie et prise en charge thérapeutique.

INTRODUCTION: Active cancer is a risk factor in the occurrence of venous thromboembolism (VTE). This is the second cause of death for these patients. In onco-urology, some cancers are associated with an increased risk of VTE. The aim of this study was to propose a focus of epidemiology and VTE therapy management. MATERIAL AND METHODS: A systematic analysis of the PubMed® database was performed through the PRISMA methodology using the followings keywords : "neoplasm", "venous thromboembolism", "prophylaxis", "pulmonary embolism", "urology". The original papers were included with a priority on: meta-analyzes, literature reviews, randomized controlled trials and good-level proof cohort studies. Only publications in English or French have been selected. RESULTS: The incidence of VTE was more important in case of renal carcinomas (3.5%/year). When surgery was proposed cystectomy was the riskiest procedure (2.6 to 11.6% VTE). Chemotherapy alone was an important risk factor increasing by a factor of six the occurrence of VTE. Hormonotherapy also increased this risk by induced hypogonadism. The curative treatment for VTE associated with cancers has to be performed through the injection of low molecular weight heparin. The implantation of a prophylactic treatment was not systematic among patients diagnosed with urological cancer. CONCLUSION: The understanding of mechanisms associated with the occurrence of VTE among these patients has enabled to improve patient management, especially those suffering from urological cancer. Undeniably, frequency of VTE is probably underestimated by urologists during clinical practice.

Increase in both angiogenic and angiostatic mediators in patients with idiopathic pulmonary fibrosis.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is associated with a marked pulmonary vascular remodeling. The aim of this study was to investigate a potential imbalance between angiogenic and angiostatic factors in this disease. METHODS AND RESULTS: Sixty-four subjects with IPF and 10 healthy control subjects (60-70 years old) were prospectively included in this multicenter study. Plasma levels of vascular endothelial growth factor A (VEGF-A), thrombospondin-1 (TSP-1) and stem cell factor (SCF) were determined by Elisa. Comparisons between IPF and controls were made using the Mann-Whitney U test. We also analyzed these soluble mediators in relation with IPF severity (DLCO<40% or>40%) predicted or total lung capacity (TLC) and forced vital capacity (FVC) (both<55% or>55% predicted) using the same test. VEGF-A plasma levels were increased in IPF vs. controls (P=0.0008) as well as those of TSP-1 (P=0.008), irrespective of the severity of the disease as reflected by DLCO, TLC or FVC values. In contrast, SCF levels were similar in IPF and controls. CONCLUSIONS: Factors modulating angiogenic responses are dysregulated in patients with IPF with increases in VEGF-A and TSP-1. The serial assessment of VEGF-A and TSP-1 during the follow-up and the search for potential relationships with the outcome of the disease might give us hints to the clinical implication of these results.

[Clinical development of anti-FXII therapeutics as a target in thrombo-inflammation]. / Développement clinique des thérapeutiques anti-facteur XII ciblant la thrombo-inflammation.

The history of anticoagulation has evolved considerably, from non-specific drugs to molecules that directly target specific coagulation factors, such as direct oral anticoagulants (DOACs). Since last decade, DOACs are widely used in clinical practice because of their ease to use with favorable pharmacological profile and not requiring monitoring. New therapeutics targeting the contact phase of coagulation are currently under development, and could make it possible to prevent thrombotic risk without altering hemostasis, thereby reducing the risk of bleeding. Factor XII, being at the crossroads between hemostasis and inflammation, appears to be an interesting target that could limit thrombo-inflammation without increasing bleeding risk. The aim of this article is to summarize the main information concerning FXII inhibitors and to review the results of various clinical trials available to date, focusing on applications beyond hemostasis, such as in the management of hereditary angioedema.

[Human immunodeficiency virus and venous thromboembolism: Role of direct oral anticoagulants]. / Modalités du traitement de la maladie veineuse thromboembolique du patient VIH par les anticoagulants oraux directs.

Nowadays, thanks to highly active antiretroviral therapy (HAART), human immunodeficiency virus (HIV) infection is transforming into a chronic disease. The life expectancy of people living with HIV (PWH) has increased, as well as their risk of developing several co-morbidities, in particular cardiovascular diseases. In addition, the incidence of venous thromboembolism (VTE) is increased in PWH with a 2 to 10 times higher incidence when compared to the general population. Over the last decade, direct oral anticoagulants (DOACs) have been widely used in the treatment and prevention of VTE and non-valvular atrial fibrillation. DOACs are characterized by a rapid onset of activity, a predictable response and a relatively wide therapeutic window. Nevertheless, drug interactions exist between HAART and DOACs, exposing PWH to a theoretically increased bleeding or thrombotic risk. DOACs are substrates of the transport protein P-glycoprotein and/or of isoforms of cytochromes P450 pathway, which can be affected by some antiretroviral drugs. Limited guidelines are available to assist physicians with the complexity of those drug-drug interactions. The aim of this paper is to provide an updated review on the evidence of the high risk of VTE in PWH and the place of DOAC therapy in this population.

Sequential intracorneal ring segment implantation followed by transepithelial phototherapeutic keratectomy and corneal cross-linking.

PURPOSE: To evaluate the safety and visual outcomes of intrastromal corneal ring segment (ICRS) implantation followed by transepithelial phototherapeutic keratectomy (te-PTK) and corneal cross-linking (CXL) in patients with mild keratoconus. METHODS: Patients with mild keratoconus and contact lens intolerance who underwent sequential ICRS implantation followed by phototherapeutic keratectomy and corneal CXL between April 2015 and July 2018 were retrospectively included in the study. Refractive and visual outcomes, satisfaction questionnaire and complications were recorded at the last follow-up (mean 9.5 months postoperatively). RESULTS: Twenty eyes of 17 patients were enrolled, including 5 women and 15 men. The mean time between the two procedures was 16 months. Based on values before the first procedure and 9.5 months after the second procedure, significant improvements were noted in uncorrected distance visual acuity (UDVA) (0.80±0.35 logMAR vs. 0.46±0.38 logMAR), corrected distance visual acuity (CDVA) (0.38±0.23 logMAR vs. 0.13±0.16 logMAR), maximal K (56.11±4 diopters [D] vs. 50.6±3.56 D), mean K (51.87±3.43 D vs. 48.45±2.91 D), cylinder (7.99±3.94 D vs. 4.23±3.49 D), and spherical equivalent (-3.84±3.36 D vs. -0.99±2.15 D) (P<0.01). Among the outcomes, we noted 5 (25%) superficial corneal scarring (haze); 75% of eyes gained>=1 logMAR line of CDVA. In all, 94.5% of patients reported that they were satisfied with their outcomes. CONCLUSION: Combining ICRS implantation followed by te-PTK and corneal CXL appears to be a safe and effective approach for improving visual outcomes and quality of life in keratoconus patients.

Relationship between kalemia and intensive care unit admission or death in hospitalized COVID-19 patients: A cohort study.

BACKGROUND: SARS-CoV-2 uses Angiotensin-Converting Enzyme 2 as a viral gateway to the cell and could interact with the renin-angiotensin-aldosterone system. Other studies have shown kalemia abnormalities in patients with severe forms of coronavirus disease 2019. Our goal was to assess the prognosis value of kalemia within ten days of symptom offset in the COVID-19 hospitalized population. METHODS: We analyzed data from a prospective cohort that included 65 patients with COVID-19, admitted between March 15, 2020, and March 21, 2020. The study aimed at determining the relationship between baseline kalemia and the admission to an intensive care unit (ICU) or death. RESULTS: The median age of the patients was 65 [54-79] years old, and 66.2% of the patients were men. Baseline kalemia under 3.8mmol/l occurred in 31 patients (48%), including 11 patients (35.5%) who were admitted to an ICU and one patient (3.2%) who died before ICU admission. In the primary end-point analysis, the adjusted hazard ratios for admission to an ICU or death were 3.52 [95% confidence interval (CI), 1.12 to 11.04] among patients with low baseline kalemia. CONCLUSION: Our study suggests that low kalemia levels within ten days of the first symptom onset might be associated with an increased risk of intensive care unit admission or death. The future perspective should be to better understand this relationship.

Different HLA class II (DRB1 and DQB1) alleles determine either susceptibility or resistance to NMO and multiple sclerosis among the French Afro-Caribbean population.

BACKGROUND: Despite similarities, neuromyelitis optica (NMO) can be distinguished from multiple sclerosis (MS) by clinical, radiological and serological findings. OBJECTIVE: This case-control study aimed to determine whether patients with NMO or with MS in an Afro-Caribbean population originating from French West Indies shared the same or different HLA class I and II pattern distribution. METHODS: The association with HLA class II (DRB1 and DQB1) alleles was tested in 42 NMO patients, 163 MS patients and 150 healthy controls. HLA-DRB1 and DQB1 typing was undertaken on genomic DNA extracted from peripheral blood leucocytes. RESULTS: By comparison with healthy controls, significantly increased frequency of HLA-DRB1 03 (26.2% vs. 13%, odds ratio 2.4, 95% confidence interval 1.31-4.28, p after correction, cp 0.045) was observed in patients with NMO. By contrast, in MS patients, HLA-DRB1 15 (24.8% vs. 13%, odds ratio 2.21, 95% CI 1.45-3.36, cp < 0.0015), but not DRB1 03 allele, was positively associated with the disease. Moreover, a modest protective effect of HLA-DRB1 11 in the MS group, independently of DRB1 15 association, was found (13.7% vs. 7% in controls, odds ratio 0.48, p 0.006), but did not survive Bonferroni correction. CONCLUSION: In conclusion, comparison of the HLA-DRB1 and DQB1 distribution in NMO and MS in this Afro-Caribbean population shows important differences in the HLA associations among NMO and MS.

Distinct patterns of circulating endothelial cells in pulmonary hypertension.

The respective abundance of circulating endothelial cells and endothelial progenitor cells may reflect the balance between vascular injury and repair. As pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) can share features of pulmonary remodelling, we postulated that the two disorders might be associated with different types of pulmonary endothelial dysfunction. We studied 25 consecutive patients undergoing cardiac catheterisation for suspected pulmonary hypertension. Nine patients had PAH, nine had CTEPH, and seven had normal pulmonary arterial pressure and served as controls. Circulating endothelial cells were isolated with CD146-coated beads. CD34(+)CD133(+) cell and endothelial progenitor cell numbers were respectively determined by flow cytometry and cell culture, in peripheral vein and pulmonary artery blood. Plasma levels of soluble vascular endothelial growth factor (VEGF), soluble E-selectin and soluble vascular cell adhesion molecule (sVCAM) were measured by ELISA. No difference in progenitor counts or VEGF levels was found across the three groups. Compared to controls, circulating endothelial cell numbers were significantly increased in PAH but not in CTEPH, in keeping with the elevated soluble E-selectin and sVCAM levels found in PAH alone. In conclusion, PAH, in contrast to CTEPH, is associated with markers of vascular injury (circulating endothelial cells, soluble E-selectin and sVCAM) but not with markers of remodelling (endothelial progenitor cells, CD34(+)CD133(+) cells and VEGF).

Maize- or potato-derived hydroxyethyl starches: is there any thromboelastometric difference?

BACKGROUND: Hydroxyethyl starches (HES) could differ with regard to the origin, and the influence on the coagulation of the raw material is unknown. This study compared the effects of a new potato-derived HES with a maize-derived HES and two crystalloid solutions. METHODS: Whole blood from 10 healthy individuals was diluted by 20% and 40% using either non-balanced potato-derived HES 130/0.42/6:1, non-balanced maize-derived HES 130/0.4/9:1, isotonic saline or Ringer's lactate solution. Samples were analysed by thromboelastometry ROTEM(®) : Coagulation was initiated by acid ellagic [intrinsic thromboelastometry (INTEM)] or tissue factor (extrinsic thromboelastometry) with and without cytochalasin to determine the functional component of fibrinogen [cytochalasin-d-modified thromboelastometry (FIBTEM)]. Platelet count and fibrinogen activity were measured. RESULTS: No effect of raw material was found as no difference was detected among the HES solutions. Whatever the solution, progressive haemodilution impaired haemostasis in a dose-dependant manner: For INTEM, the clot formation time was increased up to 308% and the maximum clot firmness (MCF) was decreased down to 49%. As dilution increased, initiation of coagulation was also impaired. Thromboelastometric alterations were more severe with HES than with crystalloids, especially regarding fibrin polymerization explorations: MCF of FIBTEM was considerably reduced from 12[10-14] to 2[2-3] mm (P<0.05). Fibrinogen activity and platelet count were reduced by dilution in a dose-dependant manner and decreased similarly in all groups. CONCLUSION: Maize- and potato-derived HES have similar effects on coagulation. Both the starch preparations tested lead to more severe haemostatic defects than crystalloids, and impairment of fibrin polymerization appears to be a leading determinant of this coagulopathy.

[Reversibility of vertebrobasilar stenoses following treatment with corticosteroid therapy in patients with giant cell arteritis]. / Régression de sténoses intracrâniennes vertébrobasilaires symptomatiques sous corticothérapie au cours d'une maladie de Horton.

INTRODUCTION: Involvement of intracranial arteries in giant cell arteritis is a rare condition but often carries a fatal prognosis. Corticosteroids seem to be insufficient to avoid ischemic cerebral complications, and could even promote the occurrence of stroke. We report the case of a patient with giant cell arteritis who experienced recurrent cerebellar stroke caused by intracranial vertebrobasilar stenoses with a favorable outcome following treatment. CASE REPORT: A 77-year-old woman presented with a 3-month history of impaired general condition. She had new-onset headaches, jaw claudication and transient vertigo, especially when she woke-up. The brain MRI showed a recent cerebellar infarction. One week later, she was hospitalized for a clinical deterioration related to a recurrent cerebellar stroke caused by intracranial vertebro-basilar stenoses. Giant cell arteritis was confirmed on the temporal artery biopsy. A treatment with high-dose oral corticosteroids was begun associated with an intensive antiplatelet therapy. The clinical outcome was favorable with rapid improvement of gait imbalance together with a complete radiological regression of the intracranial stenoses. CONCLUSION: Ischemic stroke in giant cell intracranial arteritis is a severe condition without a well-defined treatment. Corticosteroid therapy improves intracranial stenoses caused by vasculitis but should be initially associated with an intensive antithrombotic therapy to avoid early recurrence of cerebral infarcts.

[Cannabis-induced cerebral and myocardial infarction in a young woman]. / Infarctus cérébral et myocardique après consommation de cannabis chez une femme jeune.

INTRODUCTION: Cannabis is the most consumed drug in the world particularly in young adults. Few reports have suggested a causal role of cannabis in the development of cerebral or cardiovascular events. We describe the first association of myocardial infarction and stroke after heavy cannabis consumption in a 45-year-old woman. OBSERVATION: Stroke occurred in relation with a right carotid and middle cerebral artery thrombosis after cannabis abuse. The patient was successfully treated with intravenous rt-PA. Two days after her admission, she presented a myocardial infarction due to a coronary thrombosis. Cerebral and coronary arteries were angiographically normal. Etiological tests were negative and a toxic cause in relation with cannabis consumption was concluded. CONCLUSION: Cannabis can be associated with vascular events by different mechanisms. Thrombosis may occur in cerebral and/or coronary arteries. We suggest that it might be useful to search for cannabis consumption systematically in young subjects victims of stroke and myocardial infarction.

[Bilateral intracerebral angioplasty in a patient with stroke caused by giant cell arteritis]. / Angioplastie carotidienne bilatérale chez une patiente avec infarctus cérébral sur maladie de Horton.

INTRODUCTION: Giant cell arteritis is the most frequent vasculitis and can cause stroke in about 4% of the patients. The mechanism is often hemodynamic in relation with an arterial stenosis or occlusion. Optimal treatment remains to be defined. Outcome is often poor. CASE REPORT: We report the case of a 78-year-old patient, with giant cell arteritis who developed neurological deterioration after the onset of the corticotherapy. Brain MRI revealed bilateral stroke caused by multiple preocclusive internal carotid stenosis. The patient was treated successfully with angioplasty and stenting. CONCLUSION: Endovascular treatment could constitute an interesting alternative for patients with giant cell arteritis associated with neurological deterioration after a first episode of stroke because of hemodynamic instability or at stroke recurrence. For these patients, the usual medical treatment appears to be insufficient.

[Sensory ataxic neuromyelopathy in acquired copper deficiency]. / Ataxie proprioceptive et carence en cuivre masquée.

INTRODUCTION: Neurological involvement associated with copper deficiency has been reported recently in humans and may be under-recognized. CASE REPORT: A 65-year-old patient, with past history of gastrectomy 40 years earlier, developed a myelodysplastic syndrome and then subacute onset of progressive gait ataxia and paresthesias in the lower extremities. Serum vitamin B12 level was low but neurological deterioration persisted, despite vitamin replacement therapy and normal cobalamin level. Further diagnostic investigations revealed severe copper deficiency. Copper supplementation led to hematologic improvement and neurological stabilization. CONCLUSION: Copper and vitamin B12 deficiency, due to malabsorption as a cause of progressive neuromyelopathy and hematologic manifestations, may coexist.

Respiratory mechanics and gas exchanges in the early course of COVID-19 ARDS: a hypothesis-generating study.

RATIONALE: COVID-19 ARDS could differ from typical forms of the syndrome. OBJECTIVE: Pulmonary microvascular injury and thrombosis are increasingly reported as constitutive features of COVID-19 respiratory failure. Our aim was to study pulmonary mechanics and gas exchanges in COVID-2019 ARDS patients studied early after initiating protective invasive mechanical ventilation, seeking after corresponding pathophysiological and biological characteristics. METHODS: Between March 22 and March 30, 2020 respiratory mechanics, gas exchanges, circulating endothelial cells (CEC) as markers of endothelial damage, and D-dimers were studied in 22 moderate-to-severe COVID-19 ARDS patients, 1 [1-4] day after intubation (median [IQR]). MEASUREMENTS AND MAIN RESULTS: Thirteen moderate and 9 severe COVID-19 ARDS patients were studied after initiation of high PEEP protective mechanical ventilation. We observed moderately decreased respiratory system compliance: 39.5 [33.1-44.7] mL/cmH2O and end-expiratory lung volume: 2100 [1721-2434] mL. Gas exchanges were characterized by hypercapnia 55 [44-62] mmHg, high physiological dead-space (VD/VT): 75 [69-85.5] % and ventilatory ratio (VR): 2.9 [2.2-3.4]. VD/VT and VR were significantly correlated: r2 = 0.24, p = 0.014. No pulmonary embolism was suspected at the time of measurements. CECs and D-dimers were elevated as compared to normal values: 24 [12-46] cells per mL and 1483 [999-2217] ng/mL, respectively. CONCLUSIONS: We observed early in the course of COVID-19 ARDS high VD/VT in association with biological markers of endothelial damage and thrombosis. High VD/VT can be explained by high PEEP settings and added instrumental dead space, with a possible associated role of COVID-19-triggered pulmonary microvascular endothelial damage and microthrombotic process.

Relapsing neuromyelitis optica: long term history and clinical predictors of death.

BACKGROUND: Relapsing neuromyelitis optica (RNMO) is an uncommon but devastating inflammatory disorder of the central nervous system. Long term history in a wide series of RNMO is required for better knowledge of the course of the disease and identification of patients at high risk of death. METHODS: Clinical features of patients with RNMO (88 women/eight men) obtained from the geographic Caribbean database (Cuba and French West Indies) were used to determine the progression of disability and to identify clinical predictors of death. RESULTS: Median age at onset of RNMO was 29.5 years (range 11-74). Median duration of disease was 9.5 years (1-40). Median relapse rate was 0.7 attack/patient/year (0.1-3). 66 patients experienced severe visual loss in at least one eye and 46 in both eyes. Median time from onset to unilateral and bilateral severe visual loss was 3 and 15 years, respectively. Median times to reach Kurtzke Disability Status Scale 3, 6 and 8 from onset of RNMO were 1, 8 and 22 years. There were 24 deaths (25%); within 5 years in 63% of cases. A higher attack frequency during the first year of disease (p = 0.009), blindness (p = 0.04) and sphincter signs at onset (p = 0.02) and lack of recovery of first attack (p = 0.003) were independently associated with a shorter time to death. CONCLUSION: RNMO is a very rapidly disabling disease affecting primarily young women. This study has identified clinical features that predict a poor outcome. These findings suggest that early and aggressive immunotherapy might be warranted in RNMO.