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Background: Malignant hypertension has not disappeared and remains the most severe form of hypertension. More than 100 years after its description, many points remain unanswered. Mechanisms, definitions, and optimal treatment are still controversial. In 2019, we decided to launch a prospective multicentre multidisciplinary cohort in France to try to fill these gaps., Method: This study aimed to describe the baseline characteristics of the first 302 included patients and compared these data to already published cohorts. We included patients with severe hypertension associated with severe hypertensive retinopathy and patients filling the HYP MOD (HYPertension MultiOrgan Damage) definition from a broad range of departments (cardiology, nephrology, neurology intensive care unit, emergency department, internal medicine). We collected clinical, biological, imaging, and target organ damage data at admission, along with social and demographic data. We also recorded diagnostic and therapeutic management, adverse events during hospitalization, and characteristics at discharge., Results: We enrolled 302 patients in 32 months (105/year) among 40 centres and different specialties. They mainly included young men (68%, mean age 48.7 ± 14.5 years). Target organ damage involved the eye in 86.7% of patients, kidney in 58.6%, heart in 50%, brain in 32.8%, and Thrombotic Microangiopathy stigmata in 15.6%. Patients with severe retinopathy shared characteristics similar to those included in the most important cohorts already published. We also reported several additional subgroups of interest: one-third of our patients were less than 40 years old, one-third were of non-European origin, 14.3% were included through the multiorgan damage definition, without fundus severe injuries, 22.8% were treated without the use of IV therapy, 40.9% had normal or low renin level, and almost all patients were not on antihypertensive therapy at the time of the enrolment., Conclusion: These preliminary findings already challenge long-standing dogma, raise numerous questions, and provide a solid basis to address them in ancillary studies of the cohort., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Electrocardiographic screening before subcutaneous implantable cardioverter-defibrillator (S-ICD) implantation is unsuccessful in around 10% of cases. A personalized screening method, by slightly moving the electrodes, to obtain a better R/T ratio has been described to overcome traditional screening failure., Objective: The objectives of the SIS study were to assess to what extent a personalized screening method improves eligibility for S-ICD implantation and to evaluate the inappropriate shock rate after such screening success., Methods: All consecutive patients eligible for an S-ICD implantation were prospectively recruited across 20 French centers between December 2019 and January 2022. In case of traditional screening failure, patients received a second personalized screening. If at least 1 vector was positive, the personalized screening was considered successful, and the patient was eligible for implantation., Results: The study included 474 patients (mean age, 50.4 ± 14.1 years; 77.4% men). Traditional screening was successful in 456 (96.2%) cases. This figure rose to 98.3% (n = 466; P = .002) when personalized screening was performed. All patients implanted after successful personalized screening had correct signal detection on initial device interrogation. Nevertheless, after 1-year follow-up, 3 of the 7 patients (43%) implanted with personalized screening experienced inappropriate shock vs 18 of the 427 patients (4.2%) with traditional screening and S-ICD implantation (P = .003)., Conclusion: Traditional S-ICD screening was successful in our study in a high proportion of patients. Considering the small improvement in success of screening and a higher rate of inappropriate shock, a strategy of personalized screening cannot be routinely recommended., Clinicaltrials: gov identifier: NCT04101253., (Copyright © 2024 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Malignant hypertension (MHT) crisis triggers widespread microvascular damage, particularly in the brain. Despite recent MRI evidence highlighting acute cerebral injuries during MHT crises, follow-up data remain scarce. This study seeks to fill this gap by exploring how brain MRI markers evolve following acute MHT crisis management. We conducted a retrospective analysis of brain MRI data from MHT patients admitted to Bordeaux University Hospital between 2008 and 2022. Eligible patients had at least one follow-up MRI. Analysis blinded to clinical data was performed to identify markers of posterior reversible encephalopathy syndrome (PRES), acute stroke, cerebral hemorrhage, and microangiopathy. Out of 149 patients, 47 had follow-up MRIs. Most were male (72.3%) with a mean age of 48.2 ± 10.8 years. The median interval between initial and follow-up MRI was 228 days. Follow-up MRIs revealed new strokes in 10.6% of patients, cerebral hemorrhages in 4.3%, and no cases of PRES. Additionally, more patients exhibited chronic lacunar infarcts and/or microbleeds, with overall Fazekas scores remaining stable in 66.0%, improving in 31.9%, and worsening in 2.1%. Subgroup analyses based on blood pressure control or follow-up duration showed no significant differences in MRI markers. This study sheds light on the risk of new cerebrovascular events and the dynamic changes in brain MRI markers following acute MHT crisis management. Understanding these changes could lead to improved diagnosis, personalized treatment strategies, and proactive patient care for individuals with MHT., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Stroke is a rare and severe complication of giant cell arteritis (GCA). Although early diagnosis and treatment initiation are essential, the mechanism of stroke is often related to vasculitis complicated by arterial stenosis and occlusion. Its recurrence is often attributed to early steroid resistance or late GCA relapse, so immunosuppressive treatment is often reinforced. However, many questions concerning the mechanisms of stroke remain elusive, and no review to date has examined the whole data set concerning GCA-related stroke. We therefore undertook this scoping review. GCA-related stroke does not necessarily display general signs and inflammatory parameters are sometimes normal, so clinicians should observe caution. Ischemic lesions often show patterns predating watershed areas and are associated with stenosis or thrombosis of the respective arteries, which are often bilateral. Lesions predominate in the siphon in the internal carotid arteries, whereas all the vertebral arteries may be involved with a predominance in the V3-V4 segments. Ultrasonography of the cervical arteries may reveal edema of the intima (halo sign), which is highly sensitive and specific of GCA, and precedes stenosis. The brain arteries are spared although very proximal arteritis may rarely occur, if the patient has microstructural anatomical variants. Temporal artery biopsy reveals the combination of mechanisms leading to slit-like stenosis, which involves granulomatous inflammation and intimal hyperplasia. The lumen is sometimes occluded by thrombi (<15%), suggesting that embolic lesions may also occur, although imaging studies have not provided strong evidence for this. Moreover, persistence of intimal hyperplasia might explain persisting arterial stenosis, which may account for delayed stroke occurring in watershed areas. Other possible mechanisms of stroke are also discussed. Overall, GCA-related stroke mainly involves hemodynamic mechanisms. Besides early diagnosis and treatment initiation, future studies could seek to establish specific preventive or curative treatments using angioplasty or targeting intimal proliferation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Bonnan and Debeugny.)

Background: Changes in immunoglobulin (Ig) levels may occur in association with various drugs targeting immunity, including disease-modifying drugs (DMD) and corticosteroids (CS) used to treat multiple sclerosis (MS). However, kinetics of Ig levels during the natural history of MS is poorly described., Objective: To describe the natural history of the Ig levels in MS., Methods: Monocentric retrospective study examining changes in Ig levels in relation with CS intake in a series of 304 consecutive MS patients (and 1204 samples) followed or hospitalized for 7 years in a single centre. Ig levels are routinely collected in MS patients followed in our centre., Results: IgG levels were higher in samples taken at diagnosis than in those taken after the onset of MS symptoms. This effect was also observed in patients remaining free of DMD or CS since onset. On the other hand, overall Ig levels remained stable across fixed time points ranging from 1 to 20 years after onset CONCLUSION: An unanticipated finding of this study was the transient higher IgG levels in samples taken at onset, which suggests that strong inflammatory processes may occur early., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023. Published by Elsevier B.V.)

Background: Changes in immunoglobulin (Ig) levels may occur in association with various drugs targeting immunity, including those used to treat multiple sclerosis (MS). However, influence of high-dose corticosteroids (CS) is poorly described., Objective: To describe influence of disease-modifying drugs (DMD) and CS on the Ig levels., Methods: Monocentric retrospective study examining changes in Ig levels in relation with CS intake in a series of 304 consecutive MS patients (and 1204 samples) followed or hospitalized for 7 years in a single centre. Ig levels are routinely collected in MS patients followed in our centre., Results: IgG levels were significantly lower in MS patients exposed to CS infusion during the last 24 months. IgG levels were also lower in DMD-treated patients exposed to CS. DMD-specific decrease of IgM levels was confirmed in interaction with CS., Conclusion: Stratification by CS exposure suggested that a decrease in Ig levels occurring during DMD treatment was strongly associated with CS infusion. The strong and persistent effect of CS on Ig levels could be a hidden variable and should be considered in further studies targeting Ig levels., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023. Published by Elsevier B.V.)

Background: Malignant hypertension has not disappeared and is associated with a poor prognosis. Yet, so far, it has received limited attention from the medical community. Guidelines are mainly based on expert consensus and low quality evidences., Method: We set up a prospective, multicenter, observational cohort of patients with malignant hypertension. We collect at admission medical history, demographic data, ongoing treatment, clinical parameters, symptoms, care pathways, target organ status and at discharge and during follow up treatment administrated, adverse events, blood pressure level, target organ status. We aim to recruit 500 patients with malignant hypertension in 5 years, with a 5-year follow-up. Our primary objective is to assess the 5 years prognosis of these patients., Discussion: The HAMA (Hypertension Arterielle MAligne, meaning malignant hypertension) registry aims to describe the epidemiology and to assess the prognosis of malignant hypertension in a contemporary multidisciplinary cohort, with emphasis on the diversity of current management and care pathway among the different medical specialties. It may help improving our pathophysiological knowledge, and pave the way to update the definition of this particular form of hypertension. The multidisciplinary network developed in the wake of this project is expected to facilitate the set up therapeutic trials, laying the ground for evidence-based recommendations., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Acute and diffuse microvascular damage characterizes malignant hypertension (MHT), the deadliest form of hypertension (HTN). Although its ophthalmological, renal and cardiological repercussions are well known, brain involvement is considered rare with few descriptions, although it is one of the main causes of death. We hypothesized that brain MRI abnormalities are common in MHT, even in patients without objective neurological signs., Method: We analyzed retrospectively the brain MRI of patients admitted for acute MHT between 2008 and 2018 in Bordeaux University Hospital, regardless of their neurological status. A trained operator analyzed every brain MRI, looking for posterior reversible encephalopathy syndrome (PRES), ischemic stroke, intracerebral hematoma (ICH) and microangiopathy markers. We included 58 patients without neurological signs, 66% were men, and mean age was 45.6 ± 11.3 years., Results: Brain MRI were normal in 26% of patients but we found at least one acute abnormality on brain MRI in 29% and an Small Vessel Disease score (SVD score) of two or higher in 52%. In patients with neurological signs, these findings were 9, 53 and 70%, respectively. A PRES was found in 16% of asymptomatic patients and 31% had an ischemic stroke and/or a cerebral hematoma., Conclusion: PRES, recent hematoma, ischemic stroke and severe cerebral microangiopathy are common findings in MHT patients without neurological signs on admission. The impact of these findings on patient management, and their cerebrovascular and cognitive prognostic value, should be established. Brain MRI might need to become systematic in patients suffering from MHT episodes., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: The progressive phase of multiple sclerosis (MS) is characterized by an intrathecal (IT) compartmentalization of inflammation, involving B-cells within meningeal follicles, and resisting all the available immunosuppressive treatments. A new therapeutic paradigm may be to target this inflammation by injecting immunosuppressive drugs inside the central nervous system compartment., Methods: We designed a single-center, open-label, randomized, controlled, phase II study designed to evaluate the safety and efficacy of IT rituximab in progressive MS (EFFRITE trial; ClinicalTrial Registration NCT02545959). Patients were randomized into three arms (1 : 1 : 1): control group, IT rituximab (20 mg, IT) group, and intravenous+IT (IV+IT) group. The main outcome was a change in levels of CSF biomarkers of inflammation (osteopontin). Secondary outcomes were changes in levels of CSF biomarkers of axonal loss (neurofilament light chain) and clinical and MRI changes., Results: Ten patients were included (2 : 4 : 4). No adverse event occurred. OPN level remained stable in CSF at each time point, whereas NFL had slightly decreased (-8.7%) at day 21 ( p = 0.02). Clinical parameters remained stable and leptomeningeal enhancements remained unchanged., Conclusion: Clinical outcome and biomarkers of inflammation were not dramatically modified after IT injection of rituximab, probably due to its limited efficiency in CSF. Drug issues for future studies are discussed., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2021 Mickael Bonnan et al.)

Background: While spinal cord (SC) attacks of neuromyelitis optica spectrum disorder (NMOSD) are often devastating, signs predictive of their poor clinical outcome have been elusive until now, except for the delay in initiating plasma exchange (PE)., Objective: We studied the correlation between conventional non-standardized magnetic resonance imaging (MRI) parameters, PE treatment, and clinical data obtained at nadir and recovery., Methods: Retrospective study of first SC attacks of NMOSD., Results: Sixty-nine Afro-Caribbean NMOSD patients were included (aquaporin-4 (AQP4) antibodies positive in 65%). Median nadir and residual expanded disability status score (EDSS) were, respectively, 7.5 and 4.0. In bivariate analysis, all conventional MRI parameters were correlated with nadir and residual EDSS. In multivariate analysis, nadir EDSS correlated with lesion length ( p  = 0.022) and edema ( p  = 0.019), whereas residual EDSS correlated with T1w (T1-weighted) hypointense signal ( p  = 0.003). Gadolinium enhancement was not associated with outcome., Conclusion: A specific pattern of lesions in conventional MRI data is differentially associated with nadir and residual EDSS. Lesions associated with poor prognosis should prompt highly efficient treatment.

Introduction: Severe attacks of neuromyelitis optica spectrum disorder (NMO-SD) are improved by plasma exchange (PLEX) given as an adjunctive therapy. Initial studies failed to demonstrate a delay of PLEX treatment influenced clinical outcome; however PLEX was always used late. We examine the clinical consequences of delay in PLEX initiation on severe optic neuritis and spinal cord attacks in NMO-SD., Methods: All of our patients who suffered attacks of NMO-SD, treated in our centre by PLEX, were retrospectively considered for inclusion. Primary outcome was defined as complete improvement. Secondary poor/good outcomes were respectively defined to be the higher/lower third of Delta-Expanded Disability Status Scale (EDSS) (late minus baseline EDSS). Delays from clinical onset to PLEX initiation were categorised for multivariate analysis., Results: Of the 60 patients included, NMO-SD criteria (2015) were fulfilled in 92%. One hundred and fifteen attacks were included and received PLEX with a median of 7 days (0-54) after clinical onset. The probability to regain complete improvement continuously decreased from 50% for PLEX given at day 0 to 1%-5% after day 20. Through multivariate analysis, the baseline impairment and PLEX delay were associated with the probability to complete improvement (OR 5.3; 95% CI 1.8 to 15.9). Reducing the PLEX delay also influenced the good secondary outcome but not the poor secondary outcome., Conclusions: These results confirm an improved clinical benefit of early initiation of PLEX during severe attacks of NMO-SD. Perceiving PLEX as a rescue therapy only after steroid failure could be deleterious., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Objective: The low level of passively diffused IgG through the blood-brain barrier is sufficient to blur the estimation of intrathecal IgG synthesis (ITS). Therefore, this estimation requires a mathematical calculation derived from empirical laws, but the range of normal values in healthy controls is wide enough to prevent a precise calculation. This study investigated the precision of various methods of ITS estimations and their application to two clinical situations: plasma exchange and immune suppression targeting ITS., Methods: Based on a mathematical model of ITS, we constructed a population of healthy controls and applied a tunable ITS., Results: We demonstrate the following results: underestimation of ITS is common at individual level but true ITS is well fitted by cohorts; Q IgG increases after plasma exchange; IgG Loc calculation based on Qlim falsely increases when Q Alb decreases; the sample size required to demonstrate a decrease in ITS increases exponentially with larger Q Alb ., Interpretation: Studies evaluating changes in ITS level should be adjusted to Q Alb . Low amounts of ITS could be largely underestimated.

There are no international guidelines for an appropriate and cost-effective follow-up for resected nonsmall cell lung cancer (NSCLC). We retrospectively reviewed the outcome of NSCLC patients after curative surgery. Follow-up included physical examination and chest radiography every 3 months, and chest computed tomography (CT) scan, bronchoscopy, abdominal ultrasound, brain CT scan and bone scan every 6 months for 3 years, then every year over the following 2 years. Prognostic factors and costs were analysed. Median overall survival following surgery for NSCLC in 162 patients was 38.5 months. Recurrence occurred in 85 (52.5%) patients including 41 (48%) symptomatic subjects. Disease-free survival was similar between patients with asymptomatic recurrence versus symptomatic patients (11.4 versus 12 months; p=0.41). Recurrence was detected by physical examination or chest radiography in 47 (55.3%) patients. Curative-intent therapy was provided in 18 (41%) out of 44 patients with asymptomatic recurrence and in four (10%) out of 41 symptomatic cases (p=0.001). Median overall survival from time of recurrence was higher in asymptomatic patients than in symptomatic patients (15.5 versus 7.2 months; p=0.001). The cost per year of life gained was USD32 700 (€22 397). An extensive follow-up, with acceptable cost, may improve the outcome of patients with resected NSCLC through detection of asymptomatic recurrences; however, validation by prospective studies is required.

Background: Recently we published an analysis of environmental factors in familial Crohn's disease (CD) in Belgium. The aim of the current study was to assess pedigrees and sibships, temporal relationships among cases, and family circumstances relevant to the frequency or onset of CD., Study: Twenty-one families with 3 or more affected first-degree relatives were studied. Seventy-four patients with CD and 84 unaffected family members were interviewed together at the parental home, with the aid of a 176 item questionnaire. Pedigrees were constructed establishing which family members had the disease and their relationships within sibships. Dates of onset of disease, validation of first symptoms and circumstances potentially relevant to the onset and distribution of disease within families were among the data documented during the interviews. Sequence of disease within families, consecutive versus nonconsecutive sequence of disease within sibships, and temporal relationships among cases were tabulated., Results: In 12 of the 21 families CD occurred in a parent before CD in any children. Five affected fathers preceded 9 affected children; 7 affected mothers preceded 10 affected children. First borns were affected more frequently. Within sibships there were 21 instances (36%) when an affected sibling was consecutive in birth order with an affected sibling. When a parent had CD before the birth of the first child the "exposure interval" to CD in the children was longer (mean 22.4 y) than when the parent developed CD after the child was born (mean 11.8 y)., Conclusions: The clusterings of CD within sibships and in time suggest that there is a contagious element in the etiology of CD.

Background and Aims: Stress is often perceived by patients with inflammatory bowel disease (IBD) as the leading cause of their disease. The aim of this study was to assess whether stress, evaluated through life event (LE) occurrence, is associated with IBD onset., Methods: Incident cases of IBD, including 167 patients with Crohn's disease (CD) and 74 with ulcerative colitis (UC), were compared with two control groups, one of 69 patients with acute self-limited colitis (ASLC) and another of 255 blood donors (BDs). Stress was assessed using Paykel's self-questionnaire of LEs. Only LEs occurring within 6 months before the onset of symptoms in IBD cases and ASLC controls and before blood donation in BD controls were registered. Anxiety and depression were assessed using Bate's and Beck's questionnaires, respectively., Results: In univariate analysis, occurrence of LEs was more frequent in the 6-month period prior to diagnosis in CD cases than in UC cases or either control group. After adjustment for depression and anxiety scores as well as other characteristics such as smoking status and sociodemographic features, this association appeared no longer significant. No associations were noted between occurrence of LEs and onset of UC relative to controls., Conclusions: Despite its separate association with CD, LE occurrence does not appear to be an independent risk factor for IBD onset.

Background: Understanding of coronary anatomy is essential to the advancement of cardiac resynchronization therapy (CRT) techniques. We determined whether the difficulties associated with catheterization of the coronary sinus (CS) and its lateral branches could be overcome by a preliminary angiographical study of the coronary venous system carried out during a pre-operative coronary angiography with examination of venous return., Methods and Results: All patients were scheduled for an exploratory angiography procedure and indicated for CRT. Group A patients were implanted with a CRT device after a right arterial angiographical procedure while group B patients had a selective left angiogram including examination of venous return. Data analyzed in group B were: position of CS ostium, number and distribution of lateral branches, and ability to preselect a marginal vein suitable for catheterization. Subsequent device implantation was guided by these parameters. A total of 96 and 89 patients were included in groups A and B, respectively. Implantation success rates were not different (98% and 100%, respectively), but CS catheterization time was reduced in group B (6 minutes vs 4 minutes; P < 10(-6)) as well as total time required to position the left ventricular lead (25 minutes vs 15 minutes; P < 10(-6)), fluoroscopy exposure (7 minutes vs 5 minutes; P < 10(-6)), and volume of contrast medium required (45 mL vs 15 mL; P < 10(-6))., Conclusion: A coronary angiographical study, including examination of the coronary venous return prior to implantation of a CRT device, can simplify the device implant and allows patient-specific preselection of appropriate tools for the procedure.

Background: Environmental factors are believed to trigger the onset of Crohn's disease (CD) in genetically susceptible individuals. The aim of this study was to assess environmental and familial factors that might be etiologically related to CD., Methods: Twenty-one families with 3 or more affected first-degree relatives were studied, together with 10 matched control families. There were 74 patients with CD, 84 unaffected family members, and 59 controls. Family members were interviewed together at the parental home. A 176-item questionnaire delved into first symptoms, childhood vaccinations and diseases, food items, potable water supplies, social activities, travel, pets, and home and surrounding environment. Questions were directed specifically for 2 time-frames, childhood until age 20 and a 10-year epoch before the onset of first symptoms within a family. The possible factors linked to disease were evaluated using univariate and multivariate logistic regression., Results: There were significantly more smokers in the patients and their relatives than in controls. Patients had more appendicitis during adolescence, ate less oats, rye, and bran than controls, and consumed more unpasteurized cheese. Patients drank significantly less tap water and more well water than controls. Clustering of cases in time occurred in 13 of the 21 affected families., Conclusions: The less frequent consumption of oats, rye, and bran and the more frequent eating of unpasteurized cheeses imitate potential dietary influences on gastrointestinal flora. More importantly, our data suggest that the drinking of well water represents an important risk factor for CD.

Background & Aims: The rarity of inflammatory bowel disease (IBD) in both husband and wife is often given as an argument against an infectious origin. We registered conjugal instances of IBD in Northern France and in Belgium between 1989 and 2000., Methods: Couples were assigned to group A if both partners had symptoms of IBD before cohabitation, to group B if one spouse had IBD before cohabitation and the other experienced first symptoms afterwards, and to group C if both partners got the disease after cohabitation. Risk of IBD was assessed in their offspring., Results: Thirty conjugal instances were registered. Seventeen were concordant for Crohn's disease and 3 for ulcerative colitis; 10 were mixed. Two belonged to group A, 6 to group B, and 22 to group C. In group C, IBD occurred in the first affected spouse an average of 9 years after cohabitation and in the second spouse an average of 8.5 years later. Group C conjugal forms were more frequent than expected by chance (P < 0.02). Fifty-four children were born to 25 couples; among them 9, of whom 4 were siblings, developed Crohn's disease at a median age of 15 years., Conclusions: The frequency of conjugal forms of IBD suggests an etiologic role for environmental factors. Offspring of 2 affected parents have a high risk of developing IBD.