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OBJECTIVE The Patient Generated Index (PGI) is a personalized quality of life (QOL) measure. This secondary analysis examined its psychometric properties with people with severe mental illness. METHODS Three hundred and eleven people with severe mental illness participated in structured interviews at baseline, 9 months, and 18 months. RESULTS The PGI captured a range of self-defined life areas. PGI scores were correlated with measures of QOL, hope, and functioning, indicating concurrent (criterion) validity. The correlation with QOL, with the finding that PGI scores were significantly higher for people who were employed (n = 42) versus unemployed (n = 269) and for people without substance use disorder (n = 269) versus those with substance use disorder (n = 42), is indicative of construct validity. CONCLUSIONS AND IMPLICATIONS FOR PRACTICE The results support the suitability of the PGI as an idiographic measure for monitoring personalized QOL of people with severe mental illness. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Background Cognitive impairment is frequent and disabling in multiple sclerosis (MS). The Brief International Cognitive Assessment in MS (BICAMS) is a recent short battery usable in clinical practice for cognitive evaluation of MS patients. Objective To find cortical areas or brain volumes on magnetic resonance imaging (MRI) structural sequences associated with BICAMS scores in MS. Methods In this cross-sectional single-center study (NCT03656055, September 4, 2018), 96 relapsing remitting-MS patients under natalizumab and without recent clinical or radiological inflammation were included. Patients underwent brain MRI and the three BICAMS tests, evaluating information processing speed (SDMT), visuo-spatial memory (BVMT-R), and verbal memory (FVLT). Results Cortical thickness in the left frontal superior and the right precentral gyri was associated with BVMT-R scores whereas cortical thickness in the left Broca's area and the right superior temporal gyrus was associated with FVLT scores. We observed associations between white matter inflammatory lesions connected to these cortical regions and BICAMS subscores. Conclusions BICAMS scores are associated with specific cortical areas, the cognitive domain matching the known functions of the cortical area. Specific cognitive impairments in MS may be associated with specific cortical regions, themselves influenced by white matter inflammatory lesions and demographical parameters (age, sex, education level).

Introduction Carotid angioplasty and stenting (CAS) of the cervical segment is a safe and effective procedure for the treatment of carotid artery disease. In rare cases, this procedure causes intracranial hemorrhage (ICH), which is described most often as an ipsilateral intra-parenchymal hematoma. This ICH is the result of a cerebral hyperperfusion syndrome (CHS). Isolated subarachnoid hemorrhage may occur exceptionally, with only 9 cases that have been reported in the literature. Observation We reported a case of a 71-year-old man who presented a massive non-aneurysmal subarachnoid hemorrhage one hour after angioplasty and stenting of the cervical segment of the left internal carotid artery. Medical and surgical management included external ventricular drain placement. Rebleeding occurred two days later, worsening the patient's clinical condition. Finally, the patient died 2 weeks later. Comments This rare presentation of ICH following CAS allows us to discuss the risk factors, complications and management of CHS.

Background Type-17 inflammation characterizes psoriasis, a chronic skin disease. Because several inflammatory cytokines contribute to psoriasis pathogenesis, inhibiting the simultaneous production of these cytokines in TH17 cells may be beneficial in psoriasis. We found that Cav1.4, encoded by CACNA1F, was the only Cav1 calcium channel expressed in TH17 cells. Objective We sought to investigate the role of Cav1.4 expression in early TH17-activation events and effector functions, as well as its association with TH17 signature genes in lesional psoriatic (LP) skins. Methods Transcriptional gene signatures associated with CACNA1F expression were examined in LP skins by RT-PCR and in situ hybridization. Cav1 inhibitor and/or shRNA lentivectors were used to assess the contribution of Cav1.4 in TH17 activation and effector functions in a 3-dimensional skin reconstruction model. Results CACNA1F expression correlated with inflammatory cytokine expression that characterizes LP skins and was preferentially associated with RORC expression in CD4+ and CD4− cells from LP biopsies. Nicardipine, a Cav1 channel antagonist, markedly reduced inflammatory cytokine production by TH17 cells from blood or LP skin. This was associated with decreased TCR-induced early calcium events at cell membrane and proximal signaling events. The knockdown of Cav1.4 in TH17 cells impaired cytokine production. Finally, Cav1 inhibition reduced the expression of the keratinocyte genes characteristic of TH17-mediated psoriasis inflammation in human skin equivalents. Conclusions Cav1.4 channels promote TH17-cell functions both at the periphery and in inflammatory psoriatic skin.

Brain arteriovenous malformation (BAVM) is defined as abnormal communication between cerebral of arteries and veins, without capillaries. Clinically, it may involve intracranial hemorrhage or seizures. Complete spontaneous resolution, known as BAVM disappearance, has been reported in rare cases.We retrospectively collated all cases of BAVM in Lille University Hospital, from 2005 to 2018, and identified all cases of spontaneous BAVM disappearance on angiography (nidus and early venous drainage).There were 4 cases of spontaneous BAVM disappearance, in 3573 patients: i.e., prevalence of 0.1%. Sex ratio was 2:2; ages ranged from 14 to 46 years; nidus size was generally small (20mm); 3 of the 4 patients had superficial venous drainage. Revelation of BAVM was by hemorrhage in 3 cases and by seizure in 1. There were no cases of recanalization at 1 year's follow-up.Spontaneous BAVM disappearance is rare. Associated factors may include small nidus, superficial venous drainage and hemorrhage.

Sleep disordered breathing (SDB) in children is commonly described as a continuum from primary snoring (PS) to obstructive sleep apnea (OSA), based on apnea indices from polysomnography (PSG). This study evaluated the difference in neurocognitive and behavioral parameters, prior to treatment, in symptomatic pre-school children with PSG-diagnosed OSA and PS. All children had positive Pediatric Sleep Questionnaire (PSQ) results and were deemed suitable for adenotonsillectomy by an ENT surgeon. Neurocognitive and behavioral data were analyzed in pre-school children at recruitment for the POSTA study (The Pre-School OSA Tonsillectomy Adenoidectomy Study). Data were compared between PS and OSA groups, with Obstructive Apnea-Hypopnea Index, OAHI

Background It has not been investigated whether the quick sepsis-related organ failure assessment score (qSOFA), a new bedside tool for early sepsis detection, may help accelerating antibiotic initiation in ED patients with sepsis. Methods In this prospective pre/post quasi-experimental single-ED study, patients admitted with a suspected bacterial infection were managed using standard triage procedures only (baseline) or in association with qSOFA (intervention, with prioritization of patients with a qSOFA ≥ 2). Results A total of 151/328 (46.0%) and 185/350 (52.8%) patients with definite bacterial infection met the criteria for sepsis in the baseline and intervention periods, respectively. The sensitivity and specificity of a qSOFA ≥ 2 for sepsis prediction were 17.3% (95% confidence interval [CI], 13.6%–21.7%) and 98.8% (95% CI, 97.0%–99.5%). Eleven (7.3%) and 28 (13.5%) patients with sepsis in the baseline and intervention periods received a first antibiotic dose within one hour following triage (primary endpoint, absolute difference 6.2%, 95% CI [−0.5%, 12.7%], P = 0.08). The proportions of patients with sepsis receiving a first antibiotic dose within three hours following triage (39.7% [50/151] versus 36.8% [68/185], absolute difference − 2.9%, 95% CI [−13.3%, 7.3%], P = 0.65), requiring ICU admission, or dying in the hospital were similar in both periods. The median ED occupation rate at triage was 104.3% (interquartile range [IQR], 80.4%–128.3%), with a median number of 157 ED visits per day (IQR, 147–169). Conclusions A qSOFA-based triage procedure does not improve antibiotic timing and outcomes in patients with sepsis admitted to a high-volume ED. The qSOFA value at triage was poorly sensitive for early sepsis detection. Trial registration ( ClinicalTrials.gov ): NCT03299894 .

BACKGROUND For adults with intellectual disabilities living in a residential care facility, support staff, who are an integral part of their daily lives, can play an important role in supporting their sexuality. Even though multiple programmes exist, barriers remain when it comes to their application. This study aimed to identify factors affecting residential staff's perception of their role in supporting the sexuality of adults with intellectual disabilities living in a residential care facility as well as facilitators and barriers to that support. METHOD Semi-structured interviews were conducted with 12 support staff. RESULTS A thematic analysis revealed four factors, namely support staff's role, facilitators and barriers, sexuality of residents with intellectual disabilities and policies and regulations. CONCLUSION Results illustrate the importance of expanding support staff's knowledge, clarifying procedures for implementing the support staff's role and establishing a clear practise framework.

PURPOSE OF REVIEW Current immunosuppressive regimens used in kidney transplantation are sometimes ineffective and carry significant risks of morbidity and mortality. Cellular therapies are a promising alternative to prolong graft survival while minimizing treatment toxicity. We review the recently published breakthrough studies using cell therapies in kidney transplantation. RECENT FINDINGS The reviewed phase I and II trials showed that cell therapies are feasible and safe in kidney transplantation, sometimes associated with less infectious complications than traditional regimens. Regulatory T cells and macrophages were added to the induction regimen, allowing for lower immunosuppressive drug doses without higher rejection risk. Regulatory T cells are also a treatment for subclinical rejection on the 6 months biopsy. Other strategies, like bone marrow-derived mesenchymal cells, genetically modified regulatory T cells, and chimerism-based tolerance are also really promising. In addition, to improve graft tolerance, cell therapy could be used to prevent or treat viral infection after transplantation. SUMMARY Emerging data underline that cell therapy is a feasible and safe treatment in kidney transplantation. Although the evidence points to a benefit for transplant recipients, studies with standardized protocols, representative control groups, and longer follow-up are needed to answer the question definitively and guide future research.

INTRODUCTION The distinction between epidermal necrolysis [EN; including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN) and overlap syndrome] and erythema multiforme major (EMM) in children is confusing. We aimed to better describe and compare these entities. MATERIALS AND METHODS This French retrospective multicentre study included children ≤18 years old referred for EN or EMM between 1 January 2008 and 1 March 2019. According to pictures, children were reclassified into TEN/overlap, SJS or EMM/unclassified (SJS/EMM) groups and compared for epidemiological and clinical data, triggers, histology and follow-up. RESULTS We included 62 children [43 boys, median age 10 years (range 3-18)]: 16 with TEN/overlap, 11 SJS and 35 EMM. The main aetiologies were drugs in EN and infections (especially Mycoplasma pneumoniae) in EMM (P

Tuberous Sclerosis Complex (TSC) is a multisystem genetic disease characterized by cutaneous and extracutaneous hamartomas. The diagnosis is based on the association of major and minor criteria, defined by a consensus conference updated in 2012. The clinical examination of the skin is crucial because seven diagnostic criteria are dermatological: four major (hypomelanotic macules, angiofibroma or fibrous cephalic plaques, ungual fibromas, shagreen patches) and three minor criteria (confetti skin lesions, dental enamel pits, intraoral fibromas). Skin biopsy is commonly performed to assert the diagnosis of TSC when the clinical aspect is atypical. Histopathology of TSC cutaneous lesions have been poorly reported until now. In this article, we review the histologic features described in the literature and share our experience of TSC skin biopsies in our pediatric hospital specialized in genetic disorders. Both hypomelanotic lesions and cutaneous hamartomas (angiofibroma/fibrous cephalic plaques, ungual fibromas, shagreen patches) are discussed, including the recent entity called folliculocystic and collagen hamartoma, with a special emphasis on helpful clues for TSC in such lesions.

The Alternative Model for Personality Disorders (AMPD), included in the Diagnostic and Statistical Manual of Mental Disorders (5th ed.) and the World Health Organization's International Classification of Diseases (11th ed.; ICD-11) are, respectively, hybrid categorical-dimensional and dimensional frameworks for personality disorders (PDs). Both models emphasize personality dysfunction and personality traits. Previous studies investigating the links between the AMPD and ICD-11, and self-reported physical aggression have mostly focused on traits and did not take into account the potential interaction between personality dysfunction and traits. Thus, the aim of this study is to identify dysfunction*trait interactions using regression-based analysis. Outpatients with personality disorder from a specialized public clinic (N = 285) and community participants (N = 995) were recruited to complete self-report questionnaires. Some small-size, albeit significant and clinically/conceptually meaningful personality dysfunction*trait interactions were found to predict physical aggression in both samples. Interaction analyses might further inform, to some degree, about the current discussion pertaining to the potential redundancy between dysfunction and traits, the optimal personality dysfunction structure (in the case of the AMPD), as well as clinical assessment based on AMPD/ICD-11 PD frameworks.

The aim of this study is to assess international guidelines implementation concerning thromboprophylaxis strategy in myeloma patients treated with immunomodulatory drugs. This retrospective study includes multiple myeloma patients treated with immunomodulatory drugs between 2014 and 2017 in the Hematology department of a teaching hospital (Hospices Civils de Lyon, France) and followed by the multidisciplinary care plan for cancer outpatients ONCORAL (ONCological care for outpatients with ORAL anticancer drugs). Data from immunomodulatory drugs administration, thromboprophylaxis strategy and thrombotic events were collected from medical files. Adherence to 2010 International Myeloma Working Group (IMWG) guidelines was assessed. 213 patients received at least one immunomodulatory drug: lenalidomide (60.9%), pomalidomide (24.0%) and thalidomide (15.1%). About two third of treatment lines (66.2%) were in accordance with IMWG recommendations. Among the others, 30.5% and 69.5% had thromboprophylaxis, respectively, superior or inferior to IMWG recommendations. 37 venous thrombotic events and 4 arterial thromboembolisms (one patient experienced both a stroke and deep venous thrombosis simultaneously) were reported. Thromboprophylaxis was systematically performed in myeloma patients treated with immunomodulatory drugs in this real-life retrospective cohort. However, the choice of anticoagulant or anti-platelet agent remains debatable, as adherence to existing guidelines was variable.

The onset of blisters in a neonate or an infant is often a source of great concern for both parents and physicians. A blistering rash can reveal a wide range of diseases with various backgrounds (infectious, genetic, autoimmune, drug-related, traumatic, etc.), so the challenge for the dermatologist and the pediatrician is to quickly determine the etiology, between benign causes and life-threatening disorders, for a better management of the patient. Clinical presentation can provide orientation for the diagnosis, but skin biopsy is often necessary in determining the cause of blister formations. In this article, we will provide information on the skin biopsy technique and discuss the clinical orientation in the case of a neonate or infant with a blistering eruption, with a focus on the histology for each etiology.

Syringomyelia is a rare disorder in which a fluid-filled cyst forms within the spinal cord, resulting in myelopathy. Meanwhile, the abnormal dilatation of the central canal is referred to as hydromyelia or slit-like syrinx. The most prevailing classification is based on anatomical features and pathogeny rather than pathophysiological mechanisms. It is usual to distinguish foraminal syringomyelia related mainly to abnormalities at the craniocervical junction, non-foraminal syringomyelia dealing with any cause of arachnoiditis (infection, inflammation, trauma…) and more rarely syringomyelia associated with intramedullary tumors. Although many pathophysiological theories have been argued over time, the prevailing one is that disturbances in cerebrospinal fluid (CSF) flow in the sub-arachnoid spaces disrupt flow velocity leading to the syrinx. Symptoms of paralysis, sensory loss and chronic pain commonly develop during the third/fourth decades of life. The natural history of syringomyelia is typically one of gradual, stepwise neurological deterioration extending over many years. Diagnosis is based on magnetic resonance imaging (MRI) including excellent morphological sequences (T1-, T2-, FLAIR-, T2*-, enhanced T1-) and dynamic MRI with careful study of CSF velocity (CISS, cine-MR sequences). Surgical management is at first dedicated to treat the cause of the syringomyelia, mainly to re-establish a physiological CSF pathway in the subarachnoid spaces. Mostly, the surgical goal is to enlarge the craniocervical junction with duraplasty. Other surgical strategies such as arachnoidolysis or shunt procedures are performed based on the pathogenic mechanisms or as second-line treatment. Medical treatments are also necessary as chronic pain is the main long-lasting symptom. As evolutive syringomyelia is a severe disease with a high impact on quality of life, it is recommended to treat without delay. There is no evidence for surgery for incidental asymptomatic syringomyelia or hydromyelia. Finally, syringomyelia associated with intramedullary tumors resolves spontaneously after tumor resection. Syringomyelia is a rare disease, which requires a dedicated multidisciplinary approach, emphasizing the need for a nationwide scientific organization so as to offer optimal care to the patient.

Primary hyperoxalurias are rare disease with autosomal recessive inheritance; they often lead to kidney failure and can lead to life-threatening conditions, especially in early onset forms. There are three types, responding to distinct enzyme deficits. Type 1 represents 85% of cases and results from an enzyme deficiency (alanine-glyoxylate aminotransferase) in the peroxisomes of the liver, causing hyperoxaluria leading to urolithiasis with or without nephrocalcinosis. As glomerular filtration decreases, a systemic overload appears and spares no organ. Treatment has hitherto been based on combined liver and kidney transplantation, with significant mortality and morbidity. The recent introduction of interfering RNA treatments opens up new perspectives. By blocking an enzymatic synthesis (glycolate oxidase or lacticodehydrogenase a) upstream of the deficit that causes the disease, oxaluria normalizes and the tolerance of the drug (administered by injection every 1 to 3 months) is good. This strategy will help prevent kidney failure in patients treated early and avoid liver transplantation in those who are diagnosed at an advanced stage of kidney failure.

Health and logistical needs in emergencies have been well recognised. The last 7 years has witnessed improved professionalisation and standardisation of care for disaster affected communities – led in part by the World Health Organisation Emergency Medical Team (EMT) initiative. Mass casualty incidents (MCIs) resulting in burn injuries present unique challenges. Burn management benefits from specialist skills, expert knowledge, and timely availability of specialist resources. With burn MCIs occurring globally, and wide variance in existing burn care capacity, the need to strengthen burn care capability is evident. Although some high-income countries have well-established disaster management plans, including burn specific plans, many do not – the majority of countries where burn mass casualty events occur are without such established plans. Developing globally relevant recommendations is a first step in addressing this deficit and increasing preparedness to deal with such disasters. Global burn experts were invited to a succession of Technical Working Group on burns (TWGB) meetings to: 1) review literature on burn care in MCIs; and 2) define and agree on recommendations for burn care in MCIs. The resulting 22 recommendations provide a framework to guide national and international specialist burn teams and health facilities to support delivery of safe care and improved outcomes to burn patients in MCIs. publishedVersion

Intraoperative MRI (iMRI) offers the possibility of acquiring intraoperatively real-time images that will guide neurosurgeons when removing brain tumors. The objective of this study was to report the existence of FLAIR abnormalities on iMRI that may occur on the margin of a brain resection and may lead to misdiagnosis of residual tumor.We retrospectively analyzed intraoperative MRI (iMRI) in 21 consecutive patients who underwent surgery for a low-grade glioma. Two readers independently reviewed iMRI images to search for the presence of a FLAIR hyperintensity surrounding the surgical cavity. For each patient, they were instructed to characterize FLAIR abnormalities on the margins of the resected area as (1) no FLAIR abnormality; (2) "linear FLAIR hyperintensity (LFH)", when a5mm linear FLAIR hyperintensity was present; or (3) "nodular FLAIR hyperintensity (NFH)", in the case of a thick and nodular FLAIR hyperintensity.LFH were present on at least one surgical margin of one third of the patients analyzed with iMRI, and vanished on follow-up MRI, confirming its transient condition; whereas NFH were linked to persistence of pre-surgical abnormalities, such as residual tumor as confirmed or by histopathological analysis of a second surgery or by its remnant on follow-up MRI.Linear FLAIR hyperintensities can be present on surgical margins analyzed by iMRI and should not be mistaken for residual tumor.

ObjectiveTo determine whether functional MRI connectivity can predict long-term cognitive function 36 months after minor stroke.MethodsSeventy-two participants with first-ever stroke were included at baseline and followed up for 36 months. A ridge regression machine learning algorithm was developed and used to predict cognitive scores 36 months poststroke on the basis of the functional networks measured using MRI at 6 months (referred to here as the poststroke cognitive impairment [PSCI] network). The prediction accuracy was evaluated in 4 domains (memory, attention/executive, language, and visuospatial functions) and compared with clinical data and other functional networks. The models' statistical significance was probed with permutation tests. The potential involvement of cortical atrophy was assessed 6 months poststroke. A second, independent dataset (n = 40) was used to validate the results and assess their generalizability.ResultsBased on the PSCI network, a machine learning model was able to predict memory, attention, visuospatial functions, and language functions 36 months poststroke (r2: 0.67, 0.73, 0.55, and 0.48, respectively). The PSCI-based model was at least as accurate as models based on other functional networks or clinical data. Specific patterns were demonstrated for the 4 cognitive domains, with involvement of the left superior frontal cortex for memory, attention, and visuospatial functions. The cortical thickness 6 months poststroke was not correlated with cognitive function 36 months poststroke. The independent validation dataset gave similar results.ConclusionsA machine learning model based on the PSCI network can predict long-term cognitive outcome after stroke.

OBJECTIVE/BACKGROUND: The need for revascularization of the distal posterior cerebral artery (PCA) in the treatment of PCA aneurysms is a contentious issue. Approaches to the PCA, such as the subtemporal route, carry significant perioperative risk. This risk at times outweighs the risk of ischemia associated with endovascular PCA sacrifice. This paper describes the use of an extreme lateral supracerebellar infratentorial (ELSCIT) approach as an alternative technique for distal PCA revascularization. METHODS: Between 2016 and 2019, 3 patients underwent a PCA bypass via the ELSCIT approach for the treatment of a PCA aneurysm. In all cases, an end-to-side anastomosis to the P2-or P3-segment of the PCA was made, with the occipital artery as a donor. Bypass procedures were followed by endovascular parent artery occlusion, without ischemic complications. RESULTS: In all 3 cases, the ELSCIT approach offered a broad enough surgical corridor to perform an occipital artery-to-PCA bypass. One patient suffered a cerebrospinal fluid leak that was surgically treated. Patients' clinical conditions were stable on follow-up (mean follow-up of 34 months). All 3 aneurysms remained occluded, and no ischemia was detected on magnetic resonance imaging. CONCLUSIONS: The ELSCIT approach offers an alternative route to the distal PCA for extracranial-to-intracranial bypass with seemingly low perioperative morbidity and good surgical access to the PCA.

Aims/hypothesis Variants close to the VPS13C/C2CD4A/C2CD4B locus are associated with altered risk of type 2 diabetes in genome-wide association studies. While previous functional work has suggested roles for VPS13C and C2CD4A in disease development, none has explored the role of C2CD4B. Methods CRISPR/Cas9-induced global C2cd4b-knockout mice and zebrafish larvae with c2cd4a deletion were used to study the role of this gene in glucose homeostasis. C2 calcium dependent domain containing protein (C2CD)4A and C2CD4B constructs tagged with FLAG or green fluorescent protein were generated to investigate subcellular dynamics using confocal or near-field microscopy and to identify interacting partners by mass spectrometry. Results Systemic inactivation of C2cd4b in mice led to marked, but highly sexually dimorphic changes in body weight and glucose homeostasis. Female C2cd4b mice displayed unchanged body weight compared with control littermates, but abnormal glucose tolerance (AUC, p = 0.01) and defective in vivo, but not in vitro, insulin secretion (p = 0.02). This was associated with a marked decrease in follicle-stimulating hormone levels as compared with wild-type (WT) littermates (p = 0.003). In sharp contrast, male C2cd4b null mice displayed essentially normal glucose tolerance but an increase in body weight (p p = 0.003) after maintenance on a high-fat and -sucrose diet vs WT littermates. No metabolic disturbances were observed after global inactivation of C2cd4a in mice, or in pancreatic beta cell function at larval stages in C2cd4a null zebrafish. Fasting blood glucose levels were also unaltered in adult C2cd4a-null fish. C2CD4B and C2CD4A were partially localised to the plasma membrane, with the latter under the control of intracellular Ca2+. Binding partners for both included secretory-granule-localised PTPRN2/phogrin. Conclusions/interpretation Our studies suggest that C2cd4b may act centrally in the pituitary to influence sex-dependent circuits that control pancreatic beta cell function and glucose tolerance in rodents. However, the absence of sexual dimorphism in the impact of diabetes risk variants argues for additional roles for C2CD4A or VPS13C in the control of glucose homeostasis in humans. Data availability The datasets generated and/or analysed during the current study are available in the Biorxiv repository (www.biorxiv.org/content/10.1101/2020.05.18.099200v1). RNA-Seq (GSE152576) and proteomics (PXD021597) data have been deposited to GEO (www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE152576) and ProteomeXchange (www.ebi.ac.uk/pride/archive/projects/PXD021597) repositories, respectively. Graphical abstract

Background The aim of this study is to determine whether severe COVID-19 patients harbour a higher risk of ICU-acquired pneumonia. Methods This retrospective multicentre cohort study comprised all consecutive patients admitted to seven ICUs for severe COVID-19 pneumonia during the first COVID-19 surge in France. Inclusion criteria were laboratory-confirmed SARS-CoV-2 infection and requirement for invasive mechanical ventilation for 48 h or more. Control groups were two historical cohorts of mechanically ventilated patients admitted to the ICU for bacterial or non-SARS-CoV-2 viral pneumonia. The outcome of interest was the development of ICU-acquired pneumonia. The determinants of ICU-acquired pneumonia were investigated in a multivariate competing risk analysis. Result One hundred and seventy-six patients with severe SARS-CoV-2 pneumonia admitted to the ICU between March 1st and 30th June of 2020 were included into the study. Historical control groups comprised 435 patients with bacterial pneumonia and 48 ones with viral pneumonia. ICU-acquired pneumonia occurred in 52% of COVID-19 patients, whereas in 26% and 23% of patients with bacterial or viral pneumonia, respectively (p p = 0.011). Conclusion COVID-19 appears an independent risk factor of ICU-acquired pneumonia in mechanically ventilated patients with pneumonia. Whether this is driven by immunomodulatory properties by the SARS-CoV-2 or this is related to particular processes of care remains to be investigated.

Avoidant/restrictive food intake disorder (ARFID) is a feeding and eating disorder that results in nutritional inadequacies, weight loss, and/or dependence on enteral feeds, and for which three clinical subtypes have been described. We present a unique case of an 11-year-old boy with rigid ARFID since infancy and features of all three ARFID subtypes. The patient presented with a life-long history of sensory aversion, limited intake and phobia of vomiting resulting in restriction to a single food item (yogurt) for more than 5 years. He presented with severe iron-deficiency anaemia, and deficiencies of vitamins A, C, D, E and zinc. We employed a multimodal therapeutic approach that incorporated elements of cognitive-behavioural therapy (CBT), family-based therapy (FBT) and pharmacological management with an antidepressant medication (sertraline) and an atypical antipsychotic agent (olanzapine). Over the course of a 7-week admission, our approach assisted the patient in successful weight restoration and incorporation of at least three new food items into his daily diet. While there are currently no first-line recommendations for ARFID management, our study lends support to the efficacy of CBT, FBT and pharmacological management for ARFID patients, including complex cases with multiple subtype features. Further research is needed to strengthen ARFID clinical guidelines.

Central response to insulin is suspected to be defective in Alzheimer’s disease (AD), but its localization in the brain remains unknown. While most insulin is secreted in the bloodstream by the pancreas, how it interacts with the blood-brain barrier (BBB) to alter brain function remains poorly defined.Here, we show that human and murine cerebral insulin receptors (INSR), particularly the long isoform INSRα-B, are concentrated in microvessels rather than in the parenchyma. Vascular concentrations of INSRα-B were lower in the parietal cortex of subjects diagnosed with AD, positively correlating with cognitive scores, leading to a shift toward a higher INSRα-A/B ratio, consistent with cerebrovascular insulin resistance in the AD brain. Vascular INSRα was inversely correlated with β-amyloid (Aβ) plaques and β-site APP cleaving enzyme 1 (BACE1), but positively correlated with insulin-degrading enzyme (IDE), neprilysin and ABCB1. Using brain cerebral intracarotid perfusion, we found that the transport rate of insulin across the BBB remained very low (-1.s-1) and was not inhibited by an INSR antagonist. However, intracarotid perfusion of insulin induced the phosphorylation of INSRβ which was restricted to microvessels. Such an activation of vascular INSR was blunted in 3xTg-AD mice, suggesting that AD neuropathology induces insulin resistance at the level of the BBB.Overall, the present data in postmortem AD brains and an animal model of AD indicate that defects in the INSR localized at the BBB strongly contribute to brain insulin resistance in AD, in association with Aβ pathology.HighlightsCirculating insulin activates brain insulin receptors in microvessels.BBB INSR contribute to cerebral insulin resistance in AD.Cognitive impairment in AD is associated with a loss of cerebrovascular INSRα-B.Loss of isoform INSRα-B is associated with increased BACE1 activity.SummaryLeclerc et al. show that circulating insulin activates cerebral insulin receptor localized on the blood-brain-barrier level (BBB), not in the parenchyma. Experiments with human brain samples and animal models provide evidence that INSR at the BBB are impaired in Alzheimer’s disease, thereby contributing to brain insulin resistance.

Body-focused repetitive behaviours (BFRBs), such as hair-pulling, skin-picking, and nail-biting, are non-functional habits associated with difficulties in emotion regulation. Although several models have been developed to explain the difficulties experienced by people suffering from BFRBs, a number of cognitive and emotional processes have yet to be explored. This study sought to investigate the psychological characteristics involved in the development and maintenance of BFRB symptoms. In particular, we aimed to evaluate the relationship of self-criticism, shame, and maladaptive cognitive emotion strategies with symptoms and examine if the relationship between perfectionism and symptoms was mediated by self-criticism and shame. Seventy-six participants from a community sample completed a number of self-report measures. Findings from our multivariate linear regression model supported that shame and maladaptive cognitive emotion regulation strategies significantly predicted BFRB symptoms. Results of our mediational analyses revealed that shame significantly mediated the relationship between perfectionism and BFRB symptoms. Interventions that target shame may be beneficial for treating these conditions. Future studies should replicate these findings with clinical populations and other BFRB subtypes.

Background Data related to long-term safety of intracoronary (IC) injection of CD133+ bone marrow stem cells (BMSC) following an acute myocardial infarction (MI) are still lacking. Methods COMPARE-AMI is a double-blind, placebo-controlled phase II clinical trial evaluating the safety and efficacy of IC injection of CD133+ enriched hematopoietic BMSC in patients with ST-elevation myocardial infarction (STEMI) and persistent left ventricular (LV) dysfunction following successful primary percutaneous coronary intervention (PCI). Herein, we report outcomes up to ten years of follow-up. Results Between November 2007 and July 2012, we enrolled 38 patients in our study. Males were 89% and the median age was 50.5 years. Baseline left ventricular ejection fraction (LVEF) was 40.0%, and 90% of lesions were located in the left anterior descending (LAD) artery. The median follow-up time was 8.5 years IQR [7.9, 10.0]. Using Kaplan-Meier methods, MACE-free survival up to 10 years was 77.3% overall. IC injection of CD133+ BMSC was associated with a similar event-free survival rate compared to placebo (87.8% vs. 66.3%, p = .37). Two cancer cases in each group were recorded. No malignant arrhythmias were observed. Conclusions IC injection of CD133+ BMSC is safe up to 10 years of follow-up. The long-term efficacy needs to be confirmed by a larger randomized trial.

To compare brain MRI findings in progressive multifocal leukoencephalopathy (PML) associated to rituximab and natalizumab treatments and HIV infection. In this retrospective, multicentric study, we analyzed brain MRI exams from 72 patients diagnosed with definite PML: 32 after natalizumab treatment, 20 after rituximab treatment, and 20 HIV patients. We compared T2- or FLAIR-weighted images, diffusion-weighted images, T2*-weighted images, and contrast enhancement features, as well as lesion distribution, especially gray matter involvement. The three PML entities affect U-fibers associated with low signal intensities on T2*-weighted sequences. Natalizumab-associated PML showed a punctuate microcystic appearance in or in the vicinity of the main PML lesions, a potential involvement of the cortex, and contrast enhancement. HIV and rituximab-associated PML showed only mild contrast enhancement, punctuate appearance, and cortical involvement. The CD4/CD8 ratio showed a trend to be higher in the natalizumab group, possibly mirroring a more efficient immune response. Imaging features of rituximab-associated PML are different from those of natalizumab-associated PML and are closer to those observed in HIV-associated PML. • Nowadays, PML is emerging as a complication of new effective therapies based on monoclonal antibodies. • Natalizumab-associated PML shows more inflammatory signs, a perivascular distribution “the milky way,” and more cortex involvement than rituximab- and HIV-associated PML. • MRI differences are probably related to higher levels of immunosuppression in HIV patients and those under rituximab therapy.

OBJECTIVES/HYPOTHESIS Laryngeal electromyography (LEMG) is a diagnostic tool for patients with suspected neurogenic abnormalities of the larynx. LEMG is often used with the assumption that any abnormality is symptom-/disease-related. We sought to determine the prevalence of abnormal LEMG findings in a group of healthy asymptomatic adults across a large age spectrum. STUDY DESIGN Open, prospective study, gender-match and age balanced by decade. METHODS Forty-six healthy participants (age 20-78) underwent LEMG, including 178 muscles. Participants had no history of voice problems, normal VHI-10, and normal flexible laryngoscopy. Qualitative and quantitative LEMG (bilateral) were performed involving the thyroarytenoid-lateral cricoarytenoid muscle complex (TA-LCA) and cricothyroid (CT) muscles. LEMG parameters included evaluation for fibrillation potentials, sharp waves, reduced recruitment, polyphasic potentials, electrical synkinesis, and measurement of turns per second. RESULTS Of participants, 4% had at least one abnormal qualitative finding (slightly reduced recruitment or two to three discrete polyphasic potentials). There were no findings of fibrillation potentials or sharp waves. There were no abnormal qualitative findings in the CT muscles tested. Of participants, 16% had at least one abnormal synkinesis finding. LEMG qualitative abnormalities and quantitative abnormalities do not appear to correlate with gender or age. CONCLUSION Abnormal qualitative and quantitative LEMG findings were uncommon and minor in severity in our group of asymptomatic healthy adults. The likelihood of abnormal LEMG results in asymptomatic adults was 2.2% for qualitative findings, 9.3% for synkinesis, and 5.4% for turns/s. LEVEL OF EVIDENCE 3 Laryngoscope, 131:2065-2069, 2021.

Background Tuberculosis (TB) is caused by Mycobacterium tuberculosis (Mtb) infection and is a major public health problem. Clinical challenges include the lack of a blood-based test for active disease. Current blood-based tests, such as QuantiFERON (QFT) do not distinguish active TB disease from asymptomatic Mtb infection. Methods We hypothesized that TruCulture, an immunomonitoring method for whole-blood stimulation, could discriminate active disease from latent Mtb infection (LTBI). We stimulated whole blood from patients with active TB and compared with LTBI donors. Mtb-specific antigens and live bacillus Calmette-Guérin (BCG) were used as stimuli, with direct comparison to QFT. Protein analyses were performed using conventional and digital enzyme-linked immunosorbent assay (ELISA), as well as Luminex. Results TruCulture showed discrimination of active TB cases from LTBI (P < .0001, AUC = .81) compared with QFT (P = .45, AUC = .56), based on an interferon γ (IFNγ) readout after Mtb antigen (Ag) stimulation. This result was replicated in an independent cohort (AUC = .89). In exploratory analyses, TB stratification could be further improved by the Mtb antigen to BCG IFNγ ratio (P < .0001, AUC = .91). Finally, the combination of digital ELISA and transcriptional analysis showed that LTBI donors with high IFNγ clustered with patients with TB, suggesting the possibility to identify subclinical disease. Conclusions TruCulture offers a next-generation solution for whole-blood stimulation and immunomonitoring with the possibility to discriminate active and latent infection., We tested TruCulture, an immunomonitoring tool, to identify active disease from latent Mtb infection. TruCulture showed improved discrimination of tuberculosis cases from LTBI as compared with QuantiFERON. Tuberculosis stratification could be further improved by the Mtb Ag:BCG IFNγ ratio.

Background: National immunisation programmes globally are at risk of suspension due to the severe health system constraints and physical distancing measures in place to mitigate the ongoing COVID-19 pandemic. We aimed to compare the health benefits of sustaining routine childhood immunisation in Africa with the risk of acquiring severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection through visiting routine vaccination service delivery points. Methods: We considered a high-impact scenario and a low-impact scenario to approximate the child deaths that could be caused by immunisation coverage reductions during COVID-19 outbreaks. In the high-impact scenario, we used previously reported country-specific child mortality impact estimates of childhood immunisation for diphtheria, tetanus, pertussis, hepatitis B, Haemophilus influenzae type b, Streptococcus pneumoniae, rotavirus, measles, meningitis A, rubella, and yellow fever to approximate the future deaths averted before 5 years of age by routine childhood vaccination during a 6-month COVID-19 risk period without catch-up campaigns. In the low-impact scenario, we approximated the health benefits of sustaining routine childhood immunisation on only the child deaths averted from measles outbreaks during the COVID-19 risk period. We assumed that contact-reducing interventions flattened the outbreak curve during the COVID-19 risk period, that 60% of the population will have been infected by the end of that period, that children can be infected by either vaccinators or during transport, and that upon child infection the whole household will be infected. Country-specific household age structure estimates and age-dependent infection-fatality rates were applied to calculate the number of deaths attributable to the vaccination clinic visits. We present benefit–risk ratios for routine childhood immunisation, with 95% uncertainty intervals (UIs) from a probabilistic sensitivity analysis. Findings: In the high-impact scenario, for every one excess COVID-19 death attributable to SARS-CoV-2 infections acquired during routine vaccination clinic visits, 84 (95% UI 14–267) deaths in children could be prevented by sustaining routine childhood immunisation in Africa. The benefit–risk ratio for the vaccinated children is 85 000 (4900–546 000), for their siblings (60 years) is 96 (14–307). In the low-impact scenario that approximates the health benefits to only the child deaths averted from measles outbreaks, the benefit–risk ratio to the households of vaccinated children is 3 (0–10); if the risk to only the vaccinated children is considered, the benefit–risk ratio is 3000 (182–21 000). Interpretation: The deaths prevented by sustaining routine childhood immunisation in Africa outweigh the excess risk of COVID-19 deaths associated with vaccination clinic visits, especially for the vaccinated children. Routine childhood immunisation should be sustained in Africa as much as possible, while considering other factors such as logistical constraints, staff shortages, and reallocation of resources during the COVID-19 pandemic. Funding: Gavi, the Vaccine Alliance; Bill & Melinda Gates Foundation.

BACKGROUND Netherton syndrome (NS) is a rare disease caused by SPINK5 mutations, featuring variable skin and hair involvement and, in many cases, allergic manifestations with a risk of lethality, particularly in infants. The clinical management of NS is challenging. OBJECTIVES To analyse the clinical manifestations of a cohort of infants with NS managed in a reference centre and to draw up recommendations for management. METHODS We conducted a monocentric analysis of patients with NS. The inclusion criteria were management in our reference centre, a histologically or molecularly confirmed diagnosis of NS and available epidemiological, clinical and laboratory data. RESULTS A total of 43 patients with NS were included. Hypernatraemia was reported in 23 cases (54%) and associated with a greater likelihood of enteral and/or parenteral nutritional support (P < 0.001). Moreover, hypernatraemia was more frequent in patients with skin manifestations at birth (P = 0.026) and in patients bearing the c.153delT mutation in SPINK5 exon 3 (P = 0.014). The need for enteral and/or parenteral nutritional support was associated with a history of hypernatraemic dehydration (P < 0.001). Several unexpected extracutaneous complications were recorded, and new mutations were reported. The death rate (9% overall) was higher among the subset of patients bearing the c.153delT deletion. CONCLUSIONS Our data emphasize that neonatal NS is a severe and sometimes lethal multisystem disorder. Patients have a high risk of variable metabolic anomalies (i.e. lethal hypernatraemia) and therefore have major nutritional needs. Cases of NS associated with c.153delT are particularly severe. Unexpected clinical manifestations broadened the phenotypic spectrum of NS. We provide recommendations on the management of the life-threatening manifestations of NS in neonates based on our multidisciplinary experience.

BACKGROUND: Coagulopathy is a common abnormality in patients with COVID-19. However, the exact incidence of venous thromboembolic event is unknown in anticoagulated, severe COVID-19 patients. OBJECTIVES: Systematic assessment of venous thromboembolism (VTE) using complete duplex ultrasound (CDU) in anticoagulated COVID-19 patients. PATIENTS AND METHODS: We performed a retrospective study in 2 French intensive care units (ICU) where CDU is performed as a standard of care. A CDU from thigh to ankle at selected sites with Doppler waveforms and images was performed early during ICU stay in patients admitted with COVID-19. Anticoagulation dose was left to the discretion of the treating physician based on the individual risk of thrombosis. Patients were classified as treated with prophylactic anticoagulation or therapeutic anticoagulation. Pulmonary embolism was systematically searched in patients with persistent hypoxemia or secondary deterioration. RESULTS: From March 19 to April 11, 2020, 26 consecutive patients with severe COVID-19 were screened for VTE. Eight patients (31%) were treated with prophylactic anticoagulation, whereas 18 patients (69%) were treated with therapeutic anticoagulation. The overall rate of VTE in patients was 69%. The proportion of VTE was significantly higher in patients treated with prophylactic anticoagulation when compared with the other group (100% vs 56%, respectively, P = .03). Surprisingly, we found a high rate of thromboembolic events in COVID-19 patients treated with therapeutic anticoagulation, with 56% of VTE and 6 pulmonary embolisms. CONCLUSION: Our results suggest considering both systematic screening of VTE and early therapeutic anticoagulation in severe ICU COVID-19 patients.

PURPOSE The benefits and risks of supplementation with antioxidants during cancer therapy have been a controversial area. Few studies have systematically evaluated dietary intake of antioxidants with toxicity and survival in childhood cancer. We sought to determine the role of dietary intake of antioxidants on rates of infections, mucositis, relapse, and disease-free survival during induction and postinduction phases of therapy among children and adolescents with acute lymphoblastic leukemia (ALL). PATIENTS AND METHODS We enrolled 794 children in a prospective clinical trial for treatment of ALL. Dietary intake was prospectively evaluated by a food frequency questionnaire. The association between dietary intake of antioxidants and treatment-related toxicities and survival were evaluated with the Benjamini-Hochberg false discovery rate (q) and logistic regression and the Kaplan-Meier method, respectively. RESULTS Dietary surveys were available for analysis from 614 (77%), and 561 (71%) participants at diagnosis and at end of induction, respectively. Of 513 participants who completed the dietary surveys at both time points, 120 (23%) and 87 (16%) experienced a bacterial infection and 22 (4%) and 55 (10%) experienced mucositis during the induction or postinduction phases of treatment, respectively. Increased intake of dietary antioxidants was associated with significantly lower rates of infection and mucositis. No association with relapse or disease-free survival was observed. Supplementation was not associated with toxicity, relapse, or survival. CONCLUSION Consumption of antioxidants through dietary intake was associated with reduced rates of infection or mucositis, with no increased risk of relapse or reduced survival. Dietary counseling on a well-balanced diet that includes an array of antioxidants from food sources alone may confer a benefit from infections and mucositis during treatment of childhood ALL.

Previous studies have suggested that mechanical revascularization in acute ischemic stroke (AIS) patients could be affected by clot histology. In this 7-T micro-MRI study, we used R2* relaxometry of clot analogs to evaluate the relationship between texture parameters of R2* maps and clot constituents.Twelve AIS clot analogs were experimentally generated to obtain a wide range of red blood cell concentrations. All clots underwent a MR acquisition using a 7-T micro-MR system. A 3D multi-echo gradient-echo sequence was performed and R2* maps were generated. First order and second order statistics of R2* histograms within the clots were calculated. Iron concentration in clots was measured using absorption spectrometry and red blood cell count (RBC) was obtained by histopathological analysis.RBC count was strongly correlated with iron concentration within clots (r=0.87, P.001). Higher RBC count and iron concentration were significantly correlated with first order parameters including: (a) global positive shift of the R2* histogram with higher '10th percentile', 'median', 'mean' and '90th percentile'; (b) increase of the global magnitude of voxel values with higher 'total energy' and 'root mean squared'; (c) greater uniformity of the voxel values with higher 'uniformity' and lower 'entropy'. Second order statistical parameters confirmed that higher RBC count and iron concentration correlated with (a) greater concentration of high gray-level values in the image; (b) more "coarse" texture of R2* maps.Texture analysis of MRI-R2* maps can accurately estimate the red blood cell count and iron content of AIS clot analogs.

WOS: 000530171600001 PubMed: 32367310 Background Secondary hyperparathyroidism (SHPT) may persist after renal transplantation (RTx), inducing hypophosphatemia and hypercalcemia that precludes the use of vitamin D analogs. The calcimimetic cinacalcet improved plasma calcium and parathyroid hormone (PTH) levels in randomized controlled trials in adults after RTx, but pediatric data are scarce. Methods In this retrospective study, we analyzed 20 pediatric patients from the Cooperative European Paediatric Renal TransplAnt Initiative (CERTAIN) Registry who received cinacalcet after RTx. The results are presented as median and interquartile range (25th-75th percentile). Results At 13.7 (11.0-16.5) years of age, 20 pediatric patients received a renal allograft. Cinacalcet was introduced at 0.4 (0.3-2.7) years post-transplant at an estimated glomerular filtration rate (eGFR) of 50 (34-66) mL/min/1.73 m(2), plasma calcium of 2.58 (2.39-2.71) mmol/L, age-standardized (z score) phosphate of - 1.7 (- 2.7-- 0.4), and PTH of 136 (95-236) ng/L. The starting dose of cinacalcet was 0.5 (0.3-0.8) mg/kg per day, with a maximum dose of 1.1 (0.5-1.3) mg/kg per day. With a follow-up of 3.0 (1.5-3.6) years on cinacalcet therapy, eGFR remained stable; PTH levels decreased to 66 (56-124) ng/L at the last follow-up (p = 0.015). One patient displayed hypocalcemia (1.8 mmol/L). Cinacalcet was withdrawn in three patients (hypocalcemia, parathyroidectomy, incompliance). Nephrocalcinosis of the graft was not reported. Conclusions This pilot study suggests that cinacalcet as off-label therapy for SHPT after pediatric RTx is efficacious in controlling post-transplant SHPT with acceptable tolerability. Continuing cinacalcet even with normal PTH can lead to dangerous life-threatening hypocalcemia. Therefore, at each subsequent visit, the need to continue cinacalcet must be assessed. Dietmar Hopp Stiftung; European Society for Paediatric Nephrology (ESPN); German Society for Paediatric Nephrology (GPN); AstellasAstellas Pharmaceuticals; NovartisNovartis The authors received financial support from the CERTAIN Registry by a grant from the Dietmar Hopp Stiftung, the European Society for Paediatric Nephrology (ESPN), and the German Society for Paediatric Nephrology (GPN), and by grants from the pharmaceutical companies Astellas and Novartis.

Introduction To prevent bleeding after native kidney biopsy (NKB), nephrologists often prescribe desmopressin, especially for patients with reduced estimated glomerular filtration rate (eGFR) at risk of uremia-related platelet dysfunction. However, only 1 randomized study has suggested a beneficial effect for desmopressin in patients with eGFR ≥60 ml/min per 1.73 m2. This retrospective cohort study aimed to evaluate desmopressin effect on postbiopsy bleeding in all patients, regardless of eGFR and other comorbidities. Methods In this retrospective cohort study, all adult patients who underwent an NKB from April 1, 2013, to April 30, 2018, in a tertiary hospital were identified. The association between desmopressin use and bleeding complications, including hemoglobin fall, transfusion, hematoma, symptomatic hematoma, urgent radiologic study, and hypotension, was analyzed using multivariable logistic regression models. Results A total of 413 native kidney biopsies were studied, 79% of which were performed after receiving desmopressin. Patients receiving desmopressin had worse chronic kidney disease (eGFR 28 vs. 45 ml/min per 1.73 m2; P < 0.001) and were more often hospitalized (48% vs. 32%; P = 0.009). Despite higher bleeding risk, patients using desmopressin had a similar likelihood of symptomatic hematomas (odds ratio [OR], 0.39; 95% confidence interval [CI], 0.13–1.14) and a lower need for urgent radiologic studies (OR, 0.33; 95% CI, 0.11–0.98). Conclusion Patients at higher risk of bleeding using desmopressin before kidney biopsy had bleeding complications similar to those not using desmopressin. These results highlight potential important clinical and financial benefits of desmopressin use before kidney biopsy., Graphical abstract

Background/Objective Neurostimulants may improve or accelerate cognitive and functional recovery after intracerebral hemorrhage (ICH), ischemic stroke (IS), or subarachnoid hemorrhage (SAH), but few studies have described their safety and effectiveness in the intensive care unit (ICU). The objective of this study was to describe amantadine and modafinil administration practices during acute stroke care starting in the ICU and to evaluate safety and effectiveness. Methods Consecutive adult ICU patients treated with amantadine and/or modafinil following acute non-traumatic IS, ICH, or SAH were evaluated. Neurostimulant administration data were extracted from the electronic medication administration record, including medication (amantadine, modafinil, or both), starting dose, time from stroke to initiation, and whether the neurostimulant was continued at hospital discharge. Patients were considered responders if they met two of three criteria within 9 days of neurostimulant initiation: increase in Glasgow coma scale (GCS) score ≥ 3 points from pre-treatment baseline, improved wakefulness or participation documented in caregiver notes, or clinical improvement documented in physical or occupational therapy notes. Potential confounders of the effectiveness assessment and adverse drug effects were also recorded. Results A total of 87 patients were evaluable during the 3.7-year study period, including 41 (47%) with ICH, 29 (33%) with IS, and 17 (20%) with SAH. The initial neurostimulant administered was amantadine in 71 (82%) patients, modafinil in 13 (15%), or both in 3 (3%) patients. Neurostimulants were initiated a median of 7 (4.25, 12.75) days post-stroke (range 1–27 days) for somnolence (77%), not following commands (32%), lack of eye opening (28%), or low GCS (17%). The most common starting dose was 100 mg twice daily for both amantadine (86%) and modafinil (54%). Of the 79 patients included in the effectiveness evaluation, 42 (53%) were considered responders, including 34/62 (55%) receiving amantadine monotherapy and 8/24 (33%) receiving both amantadine and modafinil at the time they met the definition of a responder. No patient receiving modafinil monotherapy was considered a responder. The median time from initiation to response was 3 (2, 5) days. Responders were more frequently discharged home or to acute rehabilitation compared to non-responders (90% vs 62%, p = 0.006). Among survivors, 63/72 (88%) were prescribed a neurostimulant at hospital discharge. The most common potential adverse drug effect was sleep disruption (16%). Conclusions Neurostimulant administration during acute stroke care may improve wakefulness. Future controlled studies with a neurostimulant administration protocol, prospective evaluation, and discretely defined response and safety criteria are needed to confirm these encouraging findings. Electronic supplementary material The online version of this article (10.1007/s12028-020-00986-4) contains supplementary material, which is available to authorized users.

There are very few published studies describing the treatment of segmental bone defects of the forearm using the induced membrane technique. The objectives of this study were to evaluate the time to bone union, the function of the joints above and below the treated bone segment and the patients' quality of life over the long-term. We performed a retrospective study in all patients treated by the induced membrane for a forearm bone defect over at 13-year period. Demographics, bone union, complications, functional outcomes and occupational status were collected. Six patients were included: 2 posttraumatic injuries, 1 osteomyelitis, 1 septic arthritis, 1 aseptic nonunion, 1 tumor. The average defect length was 64mm (48-110). All defects were treated with internal fixation. Bone graft was harvested from the iliac crest in two patients, the femur (using the Reamer Irrigator Aspirator technique) in three patients and the radius in one patient. Five patients achieved bone union after a mean of 4months (3-6). Three complications were observed: 1 radioulnar instability, 1 infection of the fixation device, 1 abscess. At an average 8½ years' follow-up, the pain level on the VAS was 0.6 (0-3), the Mayo Elbow Performance Score was 98 (90-100), the Herzberg score was 108 (85.6-140) and the QuickDASH was 14.9 (2.7-35). All patients returned to work. Using the induced membrane technique avoids the complications associated with vascularized autograft and yields good functional outcome and quality of life.

BACKGROUND AND PURPOSE: Transient global amnesia (TGA) is a sudden onset of anterograde and retrograde amnesia. We aimed to assess differences in terms of cortical thickness and structural brain connectome between patients with TGA (at acute and delayed postrecovery stages) and matched controls. MATERIALS AND METHODS: We report on 18 consecutive patients with TGA who underwent 3T MR imaging, including DTI and MPRAGE sequences, at the acute (mean delay postonset: 44 hours) and delayed post-recovery (mean delay: 35 days) stages. Structural connectome was assessed in patients with TGA and in 18 age- and sex-matched controls by using probabilistic fiber- tracking and segmentation of 164 cortical/subcortical structures (“nodes”). Connectivity graphs were computed and global network metrics were calculated. Network-based statistical analysis (NBS) was applied to compare patients with TGA at each stage with controls. We also compared cortical thickness between patients with TGA and healthy controls. RESULTS: Global network metrics were not altered in patients with TGA. NBS-analysis showed structural connectome alterations in patients with TGA compared with controls, in core regions involving the limbic network, with 113 nodes and 114 connections (33 left intrahemispheric, 31 right intrahemispheric, and 50 interhemispheric connections) showing significantly decreased structural connectivity (P < .05 NBS corrected, t-values ranging from 3.03 to 8.73). Lower cortical thickness compared with controls was associated with these structural alterations in patients with TGA, involving the orbitofrontal, cingulate, and inferior temporal cortices. All the abnormalities were visible at both acute and delayed postrecovery stages. CONCLUSIONS: Our preliminary study suggests there are structural abnormalities of the limbic network in patients with TGA compared with controls, including decreased structural connectivity and cortical thickness.

Objectives To provide recommendations to facilitate the management of severe thermal burns during the acute phase in adults and children. Design A committee of 20 experts was asked to produce recommendations in six fields of burn management, namely, (1) assessment, admission to specialised burns centres, and telemedicine; (2) haemodynamic management; (3) airway management and smoke inhalation; (4) anaesthesia and analgesia; (5) burn wound treatments; and (6) other treatments. At the start of the recommendation-formulation process, a formal conflict-of-interest policy was developed and enforced throughout the process. The entire process was conducted independently of any industry funding. The experts drew up a list of questions that were formulated according to the PICO model (Population, Intervention, Comparison, and Outcomes). Two bibliography experts per field analysed the literature published from January 2000 onwards using predefined keywords according to PRISMA recommendations. The quality of data from the selected literature was assessed using GRADE® methodology. Due to the current paucity of sufficiently powered studies regarding hard outcomes (i.e. mortality), the recommendations are based on expert opinion. Results The SFAR guidelines panel generated 24 statements regarding the management of acute burn injuries in adults and children. After two scoring rounds and one amendment, strong agreement was reached for all recommendations. Conclusion Substantial agreement was reached among a large cohort of experts regarding numerous strong recommendations to optimise the management of acute burn injuries in adults and children.

Tourette syndrome is a neurodevelopmental disorder which is characterized by the presence of motor and phonic tics. These tics are generally more prevalent in childhood. Tics typically reach their maximum severity before puberty, around age 10 to 12. In most patients, tic severity usually decreases during late adolescence and adulthood. However, this is not true for all individuals. To date, the developmental trajectory leading to the persistence of tics into adulthood is still poorly understood. There are very few markers that can predict the evolution of tic symptoms from childhood to adulthood. Yet, while we cannot cure Tourette syndrome, it is possible to reduce tic severity with various treatments. The most common treatments are pharmacotherapy and behavioral and cognitive-behavioral therapy. However, there appears to be a limit to the proportion of tics that can be treated, since most treatments offer an average reduction in tics of no more than 50%. Thus, at first, this article reviews recent advances in treatment and symptom progression. Next, we propose some lines of research to improve the management and treatment of people with Tourette syndrome.

Background Neuroinflammation has been recognized as an important factor in the pathogenesis of Alzheimer's disease (AD). One of the most recognized pathways in mediating neuroinflammation is the prostaglandin E2-EP1 receptor pathway. Objective Here, we examined the efficacy of the selective EP1 antagonist ONO-8713 in limiting amyloid-β (Aβ), lesion volumes, and behavioral indexes in AD mouse models after ischemic stroke. Methods Transgenic APP/PS1, 3xTgAD, and wildtype (WT) mice were subjected to permanent distal middle cerebral artery occlusion (pdMCAO) and sham surgeries. Functional outcomes, memory, anatomical outcomes, and Aβ concentrations were assessed 14 days after surgery. Results pdMCAO resulted in significant deterioration in functional and anatomical outcomes in the transgenic mice compared with the WT mice. No relevant differences were observed in the behavioral tests when comparing the ONO-8713 and vehicle-treated groups. Significantly lower cavitation (p = 0.0373) and percent tissue loss (p = 0.0247) were observed in APP/PS1 + ONO-8713 mice compared with the WT + ONO-8713 mice. However, the percent tissue injury was significantly higher in APP/PS1 + ONO-8713 mice compared with the WT + ONO-8713 group (p = 0.0373). Percent tissue loss was also significantly lower in the 3xTgAD + ONO-8713 mice than in the WT + ONO-8713 mice (p = 0.0185). ONO-8713 treatment also attenuated cortical microgliosis in APP/PS1 mice as compared with the vehicle (p = 0.0079); however, no differences were observed in astrogliosis across the groups. Finally, APP/PS1 mice presented with characteristic Aβ load in the cortex while 3xTgAD mice exhibited very low Aβ levels. Conclusion In conclusion, under the experimental conditions, EP1 receptor antagonist ONO-8713 showed modest benefits in anatomical outcomes after stroke, mainly in APP/PS1 mice.

This study aimed to assess the reliability of rectal villous tumors staging between rectal MRI and histological examination used as the Gold Standard and to investigate causes for discrepancies. The rectal 1.5 T MR scans of 40 patients followed for a histologically proven rectal villous adenoma were retrospectively included. Two independent experienced radiologists staged each tumor according to the TNM classification and described the occurrence of retraction of the rectal wall or spiculations within the associated mesorectum. A third radiologist collected tumor’s morphological characteristics. Among the 40 villous tumors studied, 25 (63%) were non-invasive and 15 (37%) were invasive. The mean volume of tumors with spiculations and retraction was significantly greater (p

The hospital admission rate for anaphylaxis is increasing especially among the youngest children and food is the leading cause of anaphylaxis in children. In 2014, an emergency action plan for accidental food allergic reactions in children has been proposed to the medical community by the French Allergology Society. Since its publication, new information (dissemination of recommendations on the management of anaphylaxis, provision of a new dosage of 0.5 mg epinephrine in one of the autoinjector available in France, confirmation of the lack of evidence of the effectiveness of oral corticosteroids in anaphylaxis, experience gained on the use of the current action plan…) has led to an update of the initial emergency action plan. As a result, the “Allergy at school” working group, in conjunction with the task forces“Food allergy” working group of the French Allergology Society, supported by various learned societies, medical and patients’ associations, is proposing an update of the emergency action plan in case of allergic reaction in children and adolescents. The aim of this initiative is to harmonize current practices and to improve the quality of the management of allergic emergencies. The present manuscript combines a rationale on the contents of the emergency kit and the epinephrine autoinjectors.

Recent research stresses that cognitive and affective processes are implicated in Tourette Syndrome (TS) and might influence treatment. The cognitive-behavioral and psychophysiological (CoPs) approach posits that negative appraisals and maladaptive action-planning elicit negative emotions and behaviors that increase muscular tension and thus the urge to tic in TS. Hence, the CoPs targets cognitive-behavioral and affective processes increasing tension prior to tic onset. This article provides clinically novel information in the implementation and utility of the CoPs approach in a severe case of a young man with TS and a range of comorbidities marked by negative cognitions and emotions as well as planning deficits with a long-term follow-up. He received 14 sessions of CoPs therapy. Tic severity significantly decreased post-treatment with maintenance up to 36-months. The process measure of action-planning improved significantly from pre-treatment to 12-months follow-up. Results support the feasibility and acceptability of the CoPs in treating complex TS cases.

Objective: Cricoid chondronecrosis is a rare entity that has significant consequences for patients. Reports of its occurrence are scattered in the literature and currently there is no comprehensive review to help guide providers. Methods: A case report from our institution is presented. A review of available literature is then provided with assessment of risk factors, signs and symptoms at presentation, laryngeal exam findings, radiologic findings, and surgical techniques. Results: Twenty-four cases of cricoid chondronecrosis were reviewed from the literature. Patient age ranged from 8 months to 76 years. A history of endotracheal intubation for various reasons was present in all but two cases, and duration of intubation ranged from 6 hours to 28 days. Patients presented with airway compromise in all but two cases—one asymptomatic patient with prior tracheostomy and another with dysphagia after radiation. Dysphonia (n = 6) and dysphagia (n = 3) were less commonly present. Subglottic stenosis (n = 19) was the most common exam finding followed by vocal fold impairment (n = 11). When CT scan findings were reported, fragmentation of the cartilage and/or hypodensity of the central lamina were described in all but one case. Interventions ranged from observation on antibiotics and steroids to surgical therapies including tracheostomy, dilation, and posterior cricoid split, with or without stent placement. Conclusions: Cricoid chondronecrosis is a serious, rare entity that can occur even after a short period of endotracheal intubation. Providers must have a high level of suspicion in patients that present with upper airway dyspnea with a history of prior intubation. Level of evidence: Level 4

Introduction: Human beings are confronted with several trying situations that generate stress. Psychopathological manifestations such as anxiety, anxiety, depression, appear as an imbalance in the personality of individuals. Stroke and its increasing frequency in terms of death but especially morbidity has become one of the leading sources of disability in the world. Its appearance is medically described as caused by vascular risk factors. Our goal was to study the impact of stress on the onset and worsening of a stroke. Methodology: This was the clinical method, the aim of which was to identify any stressful event in the patient’s life and its psychological consequences in order to establish a link between the impact of stress and the stroke; of the semi-directive clinical interview in order to leave the subject a great possibility of expression on the themes associated with our objective then the inferential descriptive method for the evaluation of psychological factors using several scales including The CISS and the STAI. The inclusion criteria were the existence of a stroke, and the existence of a good state of cognitive functions. Results: In our summary analysis, it appears that the stroke would result from chronic stress objectively detected by coping from the CISS and the STAI. The most stressful events on the Holmes and Rahe Scale were; on the family level: the death of a loved one, the illness of a loved one, incessant arguments, family tensions, family violence. On a personal level: illness, sentimental disappointment, abandonment; alcohol, drugs; and finally on the professional level, dismissal and professional conflict. Conclusion: Stress is a psychological factor that increases the occurrence of a stroke, but also constitutes a determining disturbing element in patients with one or more vascular risk factors.

Background International guidelines recommend vaccinating allogeneic hematopoietic cell transplant (HCT) recipients at 3 months after transplant, giving 3 doses of pneumococcal conjugate vaccine (PCV) followed by either a dose of 23-valent pneumococcal polysaccharide vaccine (PSV23) or a fourth PCV dose in the case of graft-versus-host disease (GvHD). However, the long-term immunity after this regimen is unknown, and there is no recommendation from 24 months after transplant regarding boosts. Our objective was to assess the antipneumococcal antibody titers and seroprotection rates of allogeneic HCT recipients years after different schedules of vaccination. Methods We assessed 100 adult HCT recipients a median of 9.3 years (range: 1.7–40) after transplant. All patients had received at least one dose of PCV and were assessed for antipneumococcal immunoglobulin G (IgG) antibody titers against the 7 serotypes shared by PCV7, PCV13, and PSV23. Sixty-six percent of the patients had been vaccinated according to the current guidelines. Results Considering an IgG titer ≥ 0.35 µg/mL as protective for each serotype, the seroprotection rate was 50% for 7/7 serotypes and 70% for 5/7 serotypes, with no differences between the different vaccination schedules. The lack of seroprotection was associated with a transplant performed not in complete remission or from a cord-blood unit, a relapse after transplant, or chronic GvHD at assessment. Conclusion Because only half of the vaccinated patients had long-term protection, pending prospective studies defining the best boost program after the initial one, we recommend the assessment of specific IgG titers starting from 24 months to decide for further doses.

Introduction The Consortium for the early identification of Alzheimer's disease–Quebec (CIMA-Q) created a research infrastructure to recruit, characterize, and track disease progression in individuals at risk of dementia. Methods CIMA-Q established standardized clinical, neuropsychological, neuroimaging, blood (plasma, serum, RNA, genomic DNA), cryopreserved peripheral blood mononuclear cells, and cerebrospinal fluid collection protocols. These data and biological materials are available to the research community. Results In phase 1, 115 persons with subjective cognitive decline, 88 with mild cognitive impairment, 31 with early probable Alzheimer's disease, and 56 older adults with no worries nor impairments received detailed clinical and cognitive evaluations as well as blood and peripheral blood mononuclear cells collections. Among them, 142 underwent magnetic resonance imaging, 29 a 18fluorodeoxyglucose positron emission tomography, and 60 a lumbar puncture. Discussion CIMA-Q provides procedures and resources to identify early biomarkers and novel therapeutic targets, and holds promise for detecting cognitive decline in Alzheimer's disease., Highlights • Well-ascertained cohort of 290 community-dwelling elderly individuals in Quebec. • Large number of individuals with subjective cognitive decline studied longitudinally. • Clinical, neuropsychology, neuroimaging, and biomaterials available for Alzheimer's disease studies.