Quantification of short echo time MRS signals with improved version of QUantitation based on quantum ESTimation algorithm.

Magnetic resonance spectroscopy offers information about metabolite changes in the organism, which can be used in diagnosis. While short echo time proton spectra exhibit more distinguishable metabolites compared with proton spectra acquired with long echo times, their quantification (and providing estimates of metabolite concentrations) is more challenging. They are hampered by a background signal, which originates mainly from macromolecules (MM) and mobile lipids. An improved version of the quantification algorithm QUantitation based on quantum ESTimation (QUEST), with MM prior knowledge (QUEST-MM), dedicated to proton signals and invoking appropriate prior knowledge on MM, is proposed and tested. From a single acquisition, it enables better metabolite quantification, automatic estimation of the background, and additional automatic quantification of MM components, thus improving its applicability in the clinic. The proposed algorithm may facilitate studies that involve patients with pathological MM in the brain. QUEST-MM and three QUEST-based strategies for quantifying short echo time signals are compared in terms of bias-variance trade-off and Cramér-Rao lower bound estimates. The performances of the methods are evaluated through extensive Monte Carlo studies. In particular, the histograms of the metabolite and MM amplitude distributions demonstrate the performances of the estimators. They showed that QUEST-MM works better than QUEST (Subtract approach) and is a good alternative to QUEST when measured MM signal is unavailable or unsuitable. Quantification with QUEST-MM is shown for 1 H in vivo rat brain signals obtained with the SPECIAL pulse sequence at 9.4 T, and human brain signals obtained, respectively, with STEAM at 4 T and PRESS at 3 T. QUEST-MM is implemented in jMRUI and will be available for public use from version 7.1.

Complete Clinicopathological Case Report of a Young Patient Dying of COVID-19-Related Stroke.

ABSTRACT: The SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) pandemic has revealed diverse neurological manifestations of coronavirus disease 2019 (COVID-19). This case report begins with a background review of the neurological effects of COVID-19, focusing on stroke, neuroinflammation, and coagulopathy. It then describes the clinical course and autopsy findings of a young patient presenting with COVID-19-associated stroke. The formal neuropathological examination is presented, along with the systemic and brain histological features. Interesting aspects include multiterritory hemorrhagic infarctions, microinfarcts throughout the cortex and white matter, and prominent mixed inflammatory cell cuffing of intracerebral blood vessels distant from the infarcts.

Marked IDO2 expression and activity related to autophagy and apoptosis in brain tissue of fatal tuberculous meningitis.

In about 1% of tuberculosis (TB) patients, Mycobacterium tuberculosis (M. tuberculosis) can disseminate to the meninges, causing tuberculous meningitis (TBM) with mortality rate up to 60%. Chronic granulomatous inflammation (non-necrotizing and necrotizing) in the brain is the histological hallmark of TBM. The tryptophan-catabolizing enzyme indoleamine 2,3-dioxygenase 1 (IDO1) and the generated kynurenine metabolites exert major effector functions relevant to TB granuloma functioning. Here we have assessed immunohistochemically IDO1 expression and activity and its effector function and that of its isoform, IDO2, in post-mortem brain tissue of patients that demised with neurotuberculosis. We also related these findings to brain tissue of fatal/severe COVID-19. In this study, IDO1 and IDO2 were abundantly expressed and active in tuberculoid granulomas and were associated with the presence of M. tuberculosis as well as markers of autophagy and apoptosis. Like in fatal/severe COVID-19, IDO2 was also prominent in specific brain regions, such as the inferior olivary nucleus of medulla oblongata and cerebellum, but not associated with granulomas or with M. tuberculosis. Spatially associated apoptosis was observed in TBM, whereas in fatal COVID-19 autophagy dominated. Together, our findings highlight IDO2 as a potentially relevant effector enzyme in TBM, which may relate to the symptomology of TBM.

Optimized quantitative magnetic resonance spectroscopy for clinical routine.

Several practical obstacles in data handling and evaluation complicate the use of quantitative localized magnetic resonance spectroscopy (qMRS) in clinical routine MR examinations. To overcome these obstacles, a clinically feasible MR pulse sequence protocol based on standard available MR pulse sequences for qMRS has been implemented along with newly added functionalities to the free software package jMRUI-v5.0 to make qMRS attractive for clinical routine. This enables (a) easy and fast DICOM data transfer from the MR console and the qMRS-computer, (b) visualization of combined MR spectroscopy and imaging, (c) creation and network transfer of spectroscopy reports in DICOM format, (d) integration of advanced water reference models for absolute quantification, and (e) setup of databases containing normal metabolite concentrations of healthy subjects. To demonstrate the work-flow of qMRS using these implementations, databases for normal metabolite concentration in different regions of brain tissue were created using spectroscopic data acquired in 55 normal subjects (age range 6-61 years) using 1.5T and 3T MR systems, and illustrated in one clinical case of typical brain tumor (primitive neuroectodermal tumor). The MR pulse sequence protocol and newly implemented software functionalities facilitate the incorporation of qMRS and reference to normal value metabolite concentration data in daily clinical routine.

Autoinflammatory Recurrent Pericarditis Associated with a New NLRP12 Mutation in a Male Adolescent.

Idiopathic recurrent pericarditis (IRP) can be the hallmark of an autoinflammatory syndrome with recurrent attacks of chest pain and symptom-free intervals following an acute episode. The recurrence rate may be 35% in the pediatric population, frequently with less severe manifestations than at the first episode. Pericarditis can be the sole clinical manifestation or may be part of a systemic autoinflammatory disease (SAID), especially in the case of a recurrence. Familial Mediterranean Fever (FMF), Tumor Necrosis Factor Receptor-Associated Periodic Syndrome (TRAPS), Mevalonate-Kinase Deficiency (MKD), nucleotide-binding oligomerization domain 2 (NOD2)-associated autoinflammatory syndrome, and others are closely related to IRP based on similar clinical manifestations and treatment responses to anti-interleukin 1 (IL-1) agents, such as anakinra, and should therefore be excluded in patients with IRP. A newly described SAID, an autosomal dominant disorder known as NLRP12-AID (nucleotide-binding leucine-rich repeat-containing receptor 12-related autoinflammatory disease) is caused by heterozygous mutations in the NLRP12 gene and most commonly affects children. Fewer than 40 pediatric patients with NLRP12-AID have been described in the medical literature, with none presenting with RP. We report a case of relapsing pericarditis responsive to anti-IL-1 therapy in a male adolescent who carried a missense mutation in the NLRP12 gene potentially causative of the excessive activation of inflammatory pathways. This is a unique case in the medical literature that associates recurrent pericarditis in an adolescent presumed to be related to the missense mutation in the NLRP12 gene. The role of the NLRP12 inflammasome in generating and maintaining recurrent pericardial inflammation should be considered.

Alcohol septal ablation in hypertrophic cardiomyopathy: For which patients?

Percutaneous and surgical therapies for septal reduction for hypertrophic cardiomyopathy have been going head-to-head for the past 20 years with similar outcomes and mortality rates, although contemporary myectomy seems to materialize its superiority. However, on closer analysis, the external validity of studies advocating myectomy does not translate to all centres. The aim of this review was to examine the most recent data on septal reduction therapy and to attempt to phenotype the appropriate patient for each of the two treatments. The key to similar low mortality rates between ventricular septal myectomy and alcohol septal ablation appears to be proper patient selection performed in high volume clinical environments. Furthermore, we analyse the role of mavacampten (the recently approved cardiac myosin inhibitor) in replacing or complementing the two septal reduction therapies.

The Impact of Monocyte to High-Density Lipoprotein Cholesterol Ratio on All-Cause and Cardiovascular Mortality in Patients with Transcatheter Aortic Valve Replacement.

BACKGROUND: Inflammation plays a significant role in the pathogenesis of aortic stenosis. This study aimed to investigate the prognostic value of the monocyte-HDL cholesterol ratio (MHR), a new inflammatory marker, in severe aortic stenosis (AS) patients who underwent transcatheter aortic valve replacement (TAVR). METHODS: A total of 125 patients with severe AS who underwent TAVR were assessed. Clinical, echocardiographic and laboratory data relevant to the research were retrospectively obtained from the patients' records. The MHR was determined by dividing the absolute monocyte count by the HDL-C value. The primary endpoints were overall and cardiovascular mortality. RESULTS: During a median follow-up time of 39 months, primary endpoints were developed in 51 (40.8%) patients (overall mortality) and 21 (16.8%) patients (cardiovascular mortality). A receiver operating characteristic (ROC) analysis showed that by using a cut-off level of 16.16, the MHR predicted the all-cause mortality with a sensitivity of 50.9% and specificity of 89.1%. In predicting cardiovascular mortality, the MHR exhibited a sensitivity of 80.9% and specificity of 70.1% when a cut-off level of 13.56 was used. In the multivariate analysis, the MHR (p < 0.0001; 95% CI: 1.06-1.15) and atrial fibrillation (p = 0.018; 95% CI: 1.11-3.38) were found to be significant predictors of overall mortality. CONCLUSIONS: This study showed a significant elevation in the MHR among patients who experienced all-cause and cardiovascular mortality and this ratio emerged as an independent predictor of all-cause death in patients with severe AS undergoing TAVR.

A proposed magnetic resonance imaging grading system for the spectrum of central neonatal parasagittal hypoxic-ischaemic brain injury.

AIM: To describe the spectrum of parasagittal injury on MRI studies performed on children following severe perinatal term hypoxia-ischaemia, using a novel MRI grading system, and propose a new central pattern correlated with neuropathologic features. METHODS: MR scans of 297 patients with perinatal term hypoxia-ischaemia were evaluated for typical patterns of brain injury. A total of 83 patients that demonstrated the central/basal ganglia-thalamus and perirolandic pattern of injury were categorised according to the degree of severity. The perirolandic injury was graded by the degree of interhemispheric widening, paracentral lobule involvement and perirolandic cortex destruction leading to a tiered categorisation. Of these 83 patients, 19 had the most severe subtype of injury. A detailed analysis of the clinical data of a subset of 11 of these 19 patients was conducted. RESULTS: We demonstrated the mild subtype in 21/83(25%), the moderate subtype in 22/83(27%) and the severe subtype in 21/83(25%). A fourth pattern was identified in 19/83(23%) patients with a diamond-shaped expansion of the interhemispheric fissure, concomitant thalamic, putaminal, hippocampal and other smaller substrate involvement indicative of the most destructive subtype. CONCLUSIONS: We propose a new MR grading system of injury at the parasagittal perirolandic region related to severe, sustained central perinatal term hypoxia-ischaemia. We also introduce a previously undescribed pattern of injury, the most severe form of this spectrum, seen especially after prolongation of the second stage of labour. This constellation of high metabolic substrate, targeted tissue destruction is consistently demonstrated by MRI, termed the massive paramedian injury pattern.

Unusual Presentation of Atrial Myxoma: A Case Report and Review of the Literature.

BACKGROUND Although rare, atrial myxoma is the most common benign cardiac tumor. The recognized triad of presenting symptoms relates to constitutional, embolic, and obstructive effects produced by the tumor. However, the presentation may be non-specific and mimic other diseases, confounding diagnosis. CASE REPORT A middle-aged woman presented with wheezing and shortness of breath. With a strong background smoking history, the initial impression was that of acute bronchospasm. She however deteriorated rapidly, with decreased consciousness and cardiac arrest requiring resuscitation. Despite intensive care management, she died within 1 day of admission. Autopsy revealed a previously undiagnosed left atrial myxoma with coronary and systemic embolization. CONCLUSIONS This case highlights an unusual presentation of atrial myxoma, resulting in fatal simultaneous embolization to the coronary and cerebral arteries. This simultaneous embolic presentation is not common, but the potential consequences are serious. This report also demonstrates that the presentation of a left-sided atrial myxoma with cardiac asthma can mimic respiratory disease and confound diagnosis. In adult patients without a history of chronic respiratory disease, the possibility of cardiac asthma should always be entertained. Furthermore, the importance of considering atrial myxoma as a cause for cardiac asthma is emphasized. The use of transthoracic echocardiogram in aiding the rapid diagnosis of atrial myxoma is recommended. Finally, the continued acknowledgement of the important contribution the academic autopsy makes in complementing and improving clinical practice remains imperative.

The use of thalidomide to treat children with tuberculosis meningitis: A review.

Much of the morbidity and mortality caused by tuberculous meningitis (TBM) is mediated by a dysregulated immune response. Effective host-directed therapy is therefore critical to improve survival and clinical outcomes. Currently only one host-directed therapy (HDT), corticosteroids, is proven to improve mortality. However, there is no evidence that corticosteroids reduce morbidity and the mechanism of action for mortality reduction is uncertain. Further, it has no proven benefit in HIV co-infected individuals. One promising host-directed therapy approach is to restrict the immunopathology arising from tumour necrosis factor (TNF)-α excess is via TNF-α inhibitors. There are accumulating data on the role of thalidomide, anti-TNF-α monoclonal antibodies (infliximab, adalimumab) and the soluble TNF-α receptor (etanercept) in TBM treatment. Thalidomide was developed nearly seventy years ago and has been a highly controversial drug. Birth defects and toxic adverse effects have limited its use but an improved understanding of its immunological mechanism of action suggest that it may have a crucial role in regulating the destructive host response seen in inflammatory conditions such as TBM. Observational studies at our institution found low dosage adjunctive thalidomide safe in treating tuberculous mass lesions and blindness related to optochiasmatic arachnoiditis, with good clinical and radiological response. In this review, we discuss possible mechanisms of action for thalidomide, based on our clinico-radiologic experience and post-mortem histopathological work. We also propose a rationale for its use in the treatment of certain TBM-related complications.

In the Wild HRI Scenario: Influence of Regulatory Focus Theory.

Research related to regulatory focus theory has shown that the way in which a message is conveyed can increase the effectiveness of the message. While different research fields have used this theory, in human-robot interaction (HRI), no real attention has been given to this theory. In this paper, we investigate it in an in the wild scenario. More specifically, we are interested in how individuals react when a robot suddenly appears at their office doors. Will they interact with it or will they ignore it? We report the results from our experimental study in which the robot approaches 42 individuals. Twenty-nine of them interacted with the robot, while the others either ignored it or avoided any interaction with it. The robot displayed two types of behavior (i.e., promotion or prevention). Our results show that individuals that interacted with a robot that matched their regulatory focus type interacted with it significantly longer than individuals that did not experience regulatory fit. Other qualitative results are also reported, together with some reactions from the participants.

Three-dimensional visualizations from a dataset of immunohistochemical stained serial sections of human brain tissue containing tuberculosis related granulomas.

This data article presents datasets associated with the research article entitled "The immunological architecture of granulomatous inflammation in central nervous system tuberculosis'' (Zaharie et al., 2020). The morphology of tuberculosis related granulomas within the central nervous system of human patients was visualized in six different three-dimensional (3D) models. Post-mortem, formalin fixed and paraffin embedded specimens from deceased tuberculous meningitis patients were immunohistochemically stained and 800 serial histologically stained sections were acquired. Images from all sections were obtained with an Olympus BX43 light microscope and structures were identified, labeled and made three-dimensional. The interactive 3D-models allows the user to directly visualize the morphology of the granulomas and to understand the localization of the granulomas. The 3D-models can be used for multiple purposes and provide both an educational source as a gold standard for further animal studies, human research and the development of in silico models on the topic of central nervous system tuberculosis.

The immunological architecture of granulomatous inflammation in central nervous system tuberculosis.

Of all tuberculosis (TB) cases, 1% affects the central nervous system (CNS), with a mortality rate of up to 60%. Our aim is to fill the 'key gap' in TBM research by analyzing brain specimens in a unique historical cohort of 84 patients, focusing on granuloma formation. We describe three different types: non-necrotizing, necrotizing gummatous, and necrotizing abscess type granuloma. Our hypothesis is that these different types of granuloma are developmental stages of the same pathological process. All types were present in each patient and were mainly localized in the leptomeninges. Intra-parenchymal granulomas were less abundant than the leptomeningeal ones and mainly located close to the cerebrospinal fluid (subpial and subependymal). We found that most of the intraparenchymal granulomas are an extension of leptomeningeal lesions which is the opposite of the classical Rich focus theory. We present a 3D-model to facilitate further understanding of the topographic relation of granulomas with leptomeninges, brain parenchyma and blood vessels. We describe innate and adaptive immune responses during granuloma formation including the cytokine profiles. We emphasize the presence of leptomeningeal B-cell aggregates as tertiary lymphoid structures. Our study forms a basis for further research in neuroinflammation and infectious diseases of the CNS, especially TB.

Biomechanical changes of hip joint following different types of corrective osteotomy--photoelastic studies.

The paper presents the results of some comparative experimental studies that show the biomechanical changes which appear following different types of corrective osteotomy. The photoelastic technique was applied to plane models. The modifications in the stress distribution on the contour after the osteotomy in comparison with the situation before surgery were studied. Three types of osteotomy are considered: valgus osteotomy, varus osteotomy and Chiari pelvis osteotomy. Using the same experimental technique, the distribution of the contact pressure at the interface between the polyethylene cup and the femoral head is investigated, for a total hip prosthesis, as the extreme solution in the case of advanced hip arthroses. Both a normal situation and the malposition of prosthetic components were analyzed.