Diagnosis of COVID-19 in Patients with Acute Pulmonary Embolism.

Acute pulmonary embolism (PE) and coronavirus disease -2019 (COVID-19) are life-threatening diseases associated with significant morbidity and mortality. Yet little is known about their co-existence.This study explored clinical and laboratory differences between PE patients who tested positive with real-time reverse-transcription polymerase chain reaction (PCR+) and those who tested negative (PCR-) for SARS-CoV-2. Also, to determine whether ferritin D-dimer ratio (FDR) and platelet D-dimer ratio (PDR) can be used to predict COVID-19 in patients with PE. Files of 556 patients who underwent a computed tomography pulmonary angography (CTPA) examination were retrospectively investigated. Out of them, 197 were tested positive and 188 negative for SARS-CoV-2. One hundred thirteen patients (57.36%) in the PCR+ group and 113 (60.11%) in the PCR- group had a diagnosis of PE. Complaints, respiratory rate, and oxygen saturation level in the blood (SpO2) were recorded at the first admission. Monocyte and eosinophil levels remained low, whereas FDR and PDR were higher in the PCR+ group. No difference was detected in ferritin, D-dimer levels, comorbidities, SpO2, and death rates between the two groups. Cough, fever, joint pain, and higher respiratory rate were more common in the PCR+ group. A decrease in white blood cell, monocyte, and eosinophil levels, whereas an increase in FDR and PDR levels may predict COVID-19 in patients with PE. PE patients complaining of cough, fever, and fatigue should undergo PCR testing as common symptoms. COVID-19 does not seem to increase the risk of mortality in patients with PE.

Opportunities for pedagogical change in Turkish medical education revealed in the wake of the COVID-19 pandemic.

Phenomenon: As the first stage of a large-scale educational design research (EDR) study focused on the complex problem of providing authentic experiential "hands-on, minds-in" learning opportunities online during a pandemic or other exigency, we conducted a literature review and we interviewed Turkish academic staff and students about their experiences during the first year of the COVID-19 Pandemic. ApproachWe interviewed faculty members, faculty members of medical education departments, and medical students from both public and private medical schools in Türkiye between October 1 and December 31, 2020. Working in pairs, we analyzed the transcripts of 49 interviews using open qualitative coding methods with satisfactory levels of coefficients of agreement. FindingsWe defined six major themes from the qualitative analysis: 1) Fear and concern were the most common reactions when first encountering the pandemic; 2) Teaching methods during the pandemic were primarily unidirectional from faculty to students. This largely one way transmission of information occurred both synchronously and asynchronously; 3) Technological support during the pandemic shutdowns was found to be challenging for both faculties and students; 4) Evaluation of learning during the pandemic was opportunistic and had questionable rigor; 5) Healthy communication was valued by both faculty and students using an array of different tools including social media; and 6) The pandemic had both negative and positive impacts on the educational processes experienced by students and provided by faculty and resulted in recommendations for new approaches to teaching and learning in the future. Medical students were primarily concerned about the susceptibility to COVID-19 of themselves and others, and how the pandemic would affect their progress toward completing their studies. Faculty were primarily concerned about the capacity of online learning to provide clinical learning opportunities and the difficulties of assessing student clinical skills using online modalities. Medical education specialists were primarily concerned about the quality of educational opportunities offered online. InsightsOur findings were similar to other studies conducted in the USA, China, United Kingdom, and other countries. However, the interviews revealed interest among faculty and medical education specialists for further investigation of experiential or active learning models that could be applied in medical education regardless of whether the delivery mode is face-to-face, online, or most likely, blended. In the next stage of our larger scale EDR study, we will design and construct prototype learning environments that incorporate experiential, active, and authentic learning design principles.

The Expression of Active CD11b Monocytes in Blood and Disease Progression in Amyotrophic Lateral Sclerosis.

Monocytes expressing the inflammation suppressing active CD11b, a beta2 integrin, may regulate neuroinflammation and modify clinical outcomes in amyotrophic lateral sclerosis (ALS). In this single site, retrospective study, peripheral blood mononuclear cells from 38 individuals living with ALS and 20 non-neurological controls (NNC) were investigated using flow cytometry to study active CD11b integrin classical (CM), intermediate (IM) and non-classical (NCM) monocytes during ALS progression. Seventeen ALS participants were sampled at the baseline (V1) and at two additional time points (V2 and V3) for longitudinal analysis. Active CD11b+ CM frequencies increased steeply between the baseline and V3 (ANOVA repeated measurement, p < 0.001), and the V2/V1 ratio negatively correlated with the disease progression rate, similar to higher frequencies of active CD11b+ NCM at the baseline (R = −0.6567; p = 0.0031 and R = 0.3862; p = 0.0168, respectively). CD11b NCM, clinical covariates and neurofilament light-chain plasma concentration at the baseline predicted shorter survival in a multivariable and univariate analysis (CD11b NCM­HR: 1.05, CI: 1.01−1.11, p = 0.013. Log rank: above median: 43 months and below median: 21.22 months; p = 0.0022). Blood samples with the highest frequencies of active CD11b+ IM and NCM contained the lowest concentrations of soluble CD11b. Our preliminary data suggest that the levels of active CD11b+ monocytes and NCM in the blood predict different clinical outcomes in ALS.

Prevalence of multiple sclerosis in an urban population of Sivas province in Turkey

Background/aim: Multiple sclerosis (MS) is a common neurological disorder that can be a leading cause of nontraumatic disability in several countries. Recent reports have indicated a moderate to high risk of MS in European countries. In this study, we examined the prevalence of MS in a well-defined urban population of provincial center in Sivas Province in Turkey. Materials and methods: This study sampled all registered residents of urban areas of provincial center in Sivas Province in April 2017 and 2018 January. All the included patients met the McDonald 2010 criteria. Medical records were reviewed, including all available previously acquired magnetic resonance imaging data. All patients were subsequently subjected to neurologic examination to confirm the MS diagnosis. Results: We identified 21 possible MS patients, with MS diagnosis confirmed in 19. The prevalence of MS was 288 per 100,000 inhabitants. Conclusion: For future studies, these high ratio results can be used in regional and national comparisons to determine cofactors contributing to the high prevalence of MS in our region and can help health-decision makers to better plan healthcare policies to improve neurological services and awareness about multifaceted clinical presentations of MS.

Varicella zoster virus infections in neurological patients: a clinical study.

BACKGROUND: Varicella zoster virus (VZV) reactivation is a common infectious disease in neurology and VZV the second most frequent virus detected in encephalitis. This study investigated characteristics of clinical and laboratory features in patients with VZV infection. METHODS: Two hundred eighty two patients with VZV reactivation that were hospitalized in the department of neurology in the time from 2005 to 2013 were retrospectively evaluated. Results from cerebrospinal fluid (CSF) analysis were available from 85 patients. RESULTS: Trigeminal rash was the most common clinical manifestation, followed by segmental rash, CNS infection, facial nerve palsy, postherpetic neuralgia, and radiculitis. MRI of the brain performed in 25/33 patients with encephalitis/meningitis did not show any signs of infection in the brain parenchyma. Only one patient showed contrast enhancement in the hypoglossal nerve. General signs of infection such as fever or elevated CRP values were found in only half of the patients. Furthermore, rash was absent in a quarter of patients with CNS infection and facial nerve palsy, and thus, infection could only be proven by CSF analysis. Although slight inflammatory CSF changes occurred in few patients with isolated rash, the frequency was clearly higher in patients with CNS infection and facial nerve palsy. CONCLUSION: Monosegmental herpes zoster is often uncomplicated and a diagnostic lumbar puncture is not essential. In contrast, CSF analysis is an essential diagnostic tool in patients with skin lesions and cranial nerve or CNS affection. In patients with neuro-psychiatric symptoms and inflammatory CSF changes analysis for VZV should be performed even in the absence of skin lesions.

Monocyte/high-density lipoprotein ratio predicts the mortality in ischemic stroke patients.

OBJECTIVE: The inflammatory process is a very important stage in the development and prognosis of acute ischemic stroke (AIS). The monocyte to high-density lipoprotein (HDL) ratio (MHR) is accepted as a novel marker for demonstrating inflammation. However, the role of MHR as a predictor of mortality in patients with AIS remains unclear. METHODS: We retrospectively enrolled 466 patients who were referred to our clinic within the first 24hours of symptom presentation and who were diagnosed with AIS between January 2008 and June 2016. Four hundred and eight controls of similar age and gender were also included. The patient group was classified into two groups according to 30-day mortality. The groups were compared in terms of monocyte counts, HDL, and MHR values. RESULTS: The patient group had significantly higher monocyte counts and lower HDL levels; therefore, this group had higher values of MHR compared to controls. Additionally, the monocyte count and MHR value were higher, and the HDL level was lower in non-surviving patients (p<0.001). The MHR value was also observed as a significant independent variable of 30-day mortality in patients with AIS (p<0.001). The optimum cut-off value of MHR in predicting the 30-day mortality for patients with AIS was 17.52 (95% CI 0.95-0.98). CONCLUSION: Our study demonstrated that a high MHR value is an independent predictor of 30-day mortality in patients with AIS.

Gain-of-function STAT1 mutations are associated with intracranial aneurysms.

Chronic mucocutaneous candidiasis, characterized by persistent or recurrent fungal infections, represents the clinical hallmark in gain-of-function (GOF) signal transducer and activator of transcription 1 (STAT1) mutation carriers. Several cases of intracranial aneurysms have been reported in patients with GOF STAT1 mutation but the paucity of reported cases likely suggested this association still as serendipity. In order to endorse this association, we link the development of intracranial aneurysms with STAT1 GOF mutation by presenting the two different cases of a patient and her mother, and demonstrate upregulated phosphorylated STAT4 and IL-12 receptor ß1 upon stimulation in patient's blood cells. We also detected increased transforming growth factor (TGF)-ß type 2 receptor expression, particularly in CD14+ cells, and a slightly higher phosphorylation rate of SMAD3. In addition, the mother of the patient developed disseminated bacille Calmette-Guérin disease after vaccination, speculating that GOF STAT1 mutations may confer a predisposition to weakly virulent mycobacteria.

The Effect of Eosinopenia on Mortality in Patients with Intracerebral Hemorrhage.

INTRODUCTION: Inflammation may determine the prognosis of intracerebral hemorrhage (ICH), which has high mortality and morbidity rates. Recent studies have increasingly demonstrated eosinopenia as a prognostic factor, particularly in bacteremia, chronic obstructive pulmonary disease, and myocardial and cerebral infarction. Nonetheless, its significance regarding the determination of prognosis in patients with ICH has not yet been clarified. MATERIALS AND METHODS: Our study included 296 patients who presented to our clinic within 24 hours of the onset of symptoms and who were diagnosed with ICH between January 2008 and June 2016, along with 180 age- and sex-matched controls. During their hospitalization, 120 of these 296 patients died. Patients and controls were compared in terms of neutrophil count/percentage and eosinophil count/percentage; these were also compared between nonsurviving and surviving patients. The significance of eosinopenia in predicting mortality was also evaluated. RESULTS: Patients had a significantly higher neutrophil count/percentage and a significantly lower eosinophil count/percentage than controls; these results were similar between nonsurviving and surviving patients (P < .001). Consequently, the patient group was divided into 4 subgroups depending on the presence of eosinopenia and/or neutrophilia. The mortality rate was highest (62%) in the group that had both eosinopenia and neutrophilia. Univariate and multivariate logistic regression analyses indicated that neutrophilia and eosinopenia were independent predictors of mortality in ICH (P = .002; P = .004) DISCUSSION: These results indicate that eosinopenia can occur in patients with ICH and that although the mechanism is unclear, eosinopenia is closely associated with mortality in these patients, particularly when accompanied by neutrophilia.

Deregulation of microRNA-181c in cerebrospinal fluid of patients with clinically isolated syndrome is associated with early conversion to relapsing-remitting multiple sclerosis.

BACKGROUND: MiRNA-181c, miRNA-633 and miRNA-922 have been reported to be deregulated in multiple sclerosis. OBJECTIVES: To investigate the association between miRNA-181c, miRNA-633 and miRNA-922 and conversion from clinically isolated syndrome (CIS) to relapsing-remitting multiple sclerosis (RRMS); and to compare microRNAs in cerebrospinal fluid (CSF) and serum with regard to dysfunction of the blood-CSF barrier. METHODS: CSF and serum miRNA-181c, miRNA-633 and miRNA-922 were retrospectively determined by quantitative real-time polymerase chain reaction in CIS patients with (CIS-RRMS) and without (CIS-CIS) conversion to RRMS within 1 year. RESULTS: Thirty of 58 CIS patients developed RRMS. Cerebrospinal fluid miRNA-922, serum miRNA-922 and cerebrospinal fluid miRNA-181c were significantly higher in CIS-RRMS compared to CIS-CIS (P=0.027, P=0.048, P=0.029, respectively). High levels of cerebrospinal fluid miRNA-181c were independently associated with conversion from CIS to RRMS in multivariate Cox regression analysis (hazard ratio 2.99, 95% confidence interval 1.41-6.34, P=0.005). A combination of high cerebrospinal fluid miRNA-181c, younger age and more than nine lesions on magnetic resonance imaging showed the highest specificity (96%) and positive predictive value (94%) for conversion from CIS to RRMS. MiRNA-181c was higher in serum than in cerebrospinal fluid (P <0.001), while miRNA-633 and miRNA-922 were no different in cerebrospinal fluid and serum. Cerebrospinal fluid/serum albumin quotients did not correlate with microRNAs in cerebrospinal fluid (all P>0.711). CONCLUSIONS: Cerebrospinal fluid miRNA-181c might serve as a biomarker for early conversion to RRMS. Moreover, our data suggest an intrathecal origin of microRNAs detected in the cerebrospinal fluid.

Administration of oral medication by parents at home.

AIMS AND OBJECTIVE: The objective of this study was to determine parents' experiences and problems with administering medication to their children at home. BACKGROUND: Parents' experiences and access to information for the treatment of their children's illnesses at home is necessary for their children's safety. DESIGN: A descriptive cross-sectional study. METHODS: Four hundred parents from children's hospital outpatient clinics were included. A questionnaire was used to determine parents' experiences and problems with administering medication to their children at home. Descriptive statistical analyses were performed using the spss software package (version 22.00). RESULTS: Antipyretics (59%) and antibiotics (25%) were the most commonly used medicines by parents without prescription. Nearly half of the parents stated that they gave liquid medicine with a household spoon. It was found that 54% of the parents whose children refused to take tablets or liquid medicine mixed these medications into foods. Treatment was delayed in 20·7% of the children who refused to take tablets and in 29·1% of the children who refused to take liquid medicine. As a result of the project, a form and device were developed as a solution to the problems experienced by parents while administering oral medication in the home environment. CONCLUSION: The results of the study showed that a significant percentage of the parents did not use the correct equipment to administer medications, used non-prescription medicines, did not administer medications at correct intervals and mixed medication into foods. RELEVANCE TO CLINICAL PRACTICE: Healthcare professionals, especially nurses, should continually evaluate medication administration by parents at home and the readmission rate in the emergency department to further improve children's health.

Fingolimod Associated Bilateral Cystoid Macular Edema-Wait and See?

Fingolimod 0.5-mg once-daily is an approved therapy for patients with relapsing-remitting multiple sclerosis (MS). Several pivotal and real-world studies have demonstrated that fingolimod is associated with the development of macular edema (ME). Herein, we present a case of a diabetic MS patient who developed severe bilateral ME during fingolimod treatment. By means of this case study we provide a detailed review about fingolimod associated macular edema (FAME), its current incidence with or without diabetes mellitus, and previous therapy attempts and outcomes in MS patients. Intravitreal administration of antibodies raised against vascular endothelial growth factor A (VEGF-A) has not yet been used in the management of FAME, however, the excellent therapeutic response in our patient may justify the use of anti-VEGF-A agents in combination with cessation of fingolimod to achieve fast resolution of FAME and to prevent visual deficits, particularly in bilateral FAME.

Acute hemorrhagic leukoencephalitis (Weston-Hurst syndrome) in a patient with relapse-remitting multiple sclerosis.

Acute hemorrhagic leukoencephalitis is a fulminant demyelinating disease and commonly considered as a rare and severe variant of acute disseminated encephalomyelitis. Here, we report the clinical, magnetic resonance imaging, and brain biopsy findings of a 35-year-old female with relapsing-remitting multiple sclerosis, who developed acute hemorrhagic leukoencephalitis. Magnetic resonance imaging revealed symmetrical hemorrhagic lesions in the basal ganglia including the thalami. Disease progression was consistent with acute hemorrhagic leukoencephalitis with rapid deterioration of consciousness and seizures. Besides hemorrhage, infiltration of neutrophils was detected in brain biopsy.Acute hemorrhagic leukoencephalitis, also known as Weston-Hurst syndrome, is an excessive immunological response of unknown etiology. So far, an association with multiple sclerosis has not been reported. The present case raises the question, whether acute hemorrhagic leukoencephalitis is a specific hyperacute form of acute disseminated encephalomyelitis, a severe and unspecific form of an immune response in the central nervous system, or belongs to the spectrum of tumefactive multiple sclerosis.

Mesoporous silica nanoparticles accommodating electrospun nanofibers as implantable local drug delivery system processed by cold atmospheric plasma and spin coating approaches.

Nanofibers (NF) and nanoparticles are attractive for drug delivery to improve the drug bioavailability and administration. Easy manipulation of NF as macroscopic bulk material give rise to potential usages as implantable local drug delivery systems (LLDS) to overcome the failures of systemic drug delivery systems such as unmet personalized needs, side effects, suboptimal dosage. In this study, poly(ethylene glycol) polyethyleneimine (mPEG:PEI) copolymer blended polyϵ-caprolactone NFs, NFblendaccommodating mesoporous silica nanoparticles (MSN) as the implantable LLDS was achieved by employing spin coating and cold atmospheric plasma (CAP) as the post-process for accommodation on NFblend. The macroporous morphology, mechanical properties, wettability, andin vitrocytocompatibility of NFblendensured their potential as an implantable LLDS and superior features compared to neat NF. The electron microscopy images affirmed of NFblendrandom fiber (average diameter 832 ± 321 nm) alignments and accessible macropores before and after MSN@Cur accommodation. The blending of polymers improved the elongation of NF and the tensile strength which is attributed as beneficial for implantable LLDS. CAP treatment could significantly improve the wettability of NF observed by the contact angle changes from ∼126° to ∼50° which is critical for the accommodation of curcumin-loaded MSN (MSN@Cur) andin vitrocytocompatibility of NF. The combined CAP and spin coating as the post-processes was employed for accommodating MSN@Cur on NFblendwithout interfering with the electrospinning process. The post-processing aided fine-tuning of curcumin dosing (∼3 µg to ∼15 µg) per dose unit and sustained zero-order drug release profile could be achieved. Introducing of MSN@Cur to cells via LLDS promoted the cell proliferation compared to MSN@Cur suspension treatments and assigned as the elimination of adverse effects by nanocarriers by the dosage form integration. All in all, NFblend-MSN@Cur was shown to have high potential to be employed as an implantable LLDS. To the best of our knowledge, this is the first study in which mPEG:PEI copolymer blend NF are united with CAP and spin coating for accommodating nano-drug carriers, which allows for NF both tissue engineering and drug delivery applications.

Natural selection and functional genetic variation in the p53 pathway.

The allele frequencies of two functional single-nucleotide polymorphisms (SNPs) in the p53 pathway, the MDM2 SNP309 and TP53 Arg72Pro, vary dramatically among populations. That the frequencies of the TP53 SNP follow a clinal distribution may suggest that selective pressure from environmental variables correlated with latitude contributed to these observed population differences. Recently, winter temperature and UV radiation were found to be significantly correlated with the TP53 and the MDM2 SNPs, respectively, in East Asians; whether these correlations are more extreme than expected based upon nonselective factors such as patterns of human migration remains unclear. Here, we genotyped these two SNPs in 971 unrelated individuals from 52 unique populations worldwide and tested for correlations with both latitude and a number of climate-related environmental variables on a global scale, controlling for these neutral processes. The TP53 SNP was associated with a significant selection signal for a few climate variables, such as short-wave radiation flux in the winter, but these signals were no longer significant after correction for multiple tests. The MDM2 SNP did not exhibit a significant signal with any climate variable. Therefore, these SNPs are unlikely to be under selective pressure driven by these variables. Thus, these data underscore the need to incorporate population history when assessing signatures of selection.

Elevated admission blood pressure and acute ischemic lesions in spontaneous intracerebral hemorrhage.

Concomitant acute ischemic lesions are detected in a subset of patients with intracerebral hemorrhage (ICH). In this study, our aim was to analyze the pattern of acute ischemic lesions detected by diffusion-weighted imaging (DWI) in patients with ICH, and to use this information, in combination with clinical characteristics of patients, to understand the underlying mechanisms of these lesions. We retrospectively analyzed patients with a diagnosis of ICH who underwent DWI within 14 days of symptom onset. We compared demographic, clinical, and imaging characteristics in patients with and without acute ischemic lesions. We also assessed the number, location, and topographic distribution of DWI bright lesions. Acute ischemic lesions were detected in 15 of 86 patients (17.4%); the lesions had a small, dot-like appearance in 13 patients (87%) and were located in an arterial territory separate from the incident ICH in 12 patients (80%). Patients with acute ischemic lesions had higher admission systolic, diastolic, and mean arterial blood pressure levels; greater periventricular leukoaraiosis burden; more microbleeds, and lower admission Glasgow Coma Scale score. In multivariate analyses, admission mean arterial blood pressure (P < .01) and Glasgow Coma Scale score (P =.03) remained as the only significant variables associated with DWI lesion positivity. Our findings highlight the role of elevated admission blood pressure in the development of concomitant acute ischemic lesions in patients with ICH. The pattern of DWI bright lesions, together with a trend toward an increased burden of leukoaraiosis and microbleeds in patients with acute ischemic lesions, suggest an underlying dysfunctional cerebral microvasculature in the etiology of these lesions.

Diagnostic Importance of PAX2, ARID1A, and FOXA1 Biomarkers in Atypical Endometrial Hyperplasia.

OBJECTIVE: To evaluate the contribution of PAX2, ARID1A, and FOXA1 biomarkers to diagnosis in cases with atypical endometrial hyperplasia (AEH). STUDY DESIGN: Descriptive Study. Place and Duration of the Study: Pathology Department of Umraniye Training and Research Hospital, from January 2018 to December 2020. METHODOLOGY: Curettage materials of 100 patients diagnosed with AEH which stained PAX2, ARID1A, and FOXA1, were evaluated. The staining patterns in the atypical endometrial glandular areas were grouped as slight-no loss, moderate loss, and complete loss / severe loss for all three biomarkers. Complete or/severe loss in AEH was considered helpful in the diagnosis. RESULTS: Complete loss / severe loss rates in curettages were 84% for PAX2, 5% for ARID1A, and 15% for FOXA1, respectively. When used in combination, complete loss / severe loss rates were 85% in at least one of the three markers, 84% in PAX2 and/or ARID1A, 85% in PAX2 and/or FOXA1, and 17% in ARID1A and/or FOXA1. CONCLUSION: Although all 3 biomarkers showed marked staining loss, PAX2 is the most sensitive biomarker for the diagnosis of AEH in curettage materials. KEY WORDS: Endometrium, Atypical hyperplasia, PAX2, ARID1A, FOXA1.

Senescent-like Blood Lymphocytes and Disease Progression in Amyotrophic Lateral Sclerosis.

BACKGROUND AND OBJECTIVES: Aging is known to exacerbate neuroinflammation, and in the neurodegenerative disorder amyotrophic lateral sclerosis (ALS), an older age is associated with a worse prognosis. We have previously shown the activation of cell senescence pathways in the proteome of peripheral blood mononuclear cells and the increase of proinflammatory cytokines in blood from individuals living with ALS. In this single-center, retrospective study, we investigated the expression of senescent-like blood mononuclear cells in ALS. METHODS: We first applied multidimensional cytometry by time-of-flight (CyTOF) to study the senescent immunophenotype of blood mononuclear cells from 21 patients with ALS and 10 healthy controls (HCs). We then used targeted flow cytometry (FC) to investigate frequencies of senescent blood lymphocytes in 40 patients with ALS and 20 HCs. Longitudinal analysis included 2 additional time points in 17 patients with ALS. Frequencies of senescent-like lymphocytes were analyzed in relation to survival. RESULTS: Unsupervised clustering of CyTOF data showed higher frequencies of senescent CD4+CD27-CD57+ T cells in patients with ALS compared with those in HCs (p = 0.0017, false discovery (FDR)-adjusted p = 0.029). Moderate to strong negative correlations were identified between CD4 T central memory-cell frequencies and survival (R = -061, p = 0.01; FDR-adjusted p < 0.1) and between CD95 CD8 cells and ALS functional rating scale revised at baseline (R = -0.72, p = 0.001; FDR-adjusted p < 0.1).Targeted FC analysis showed higher memory T regulatory cells (p = 0.0052) and memory CD8+ T cell (M-Tc; p = 0.0006) in bulbar ALS (A-B) compared with those in limb ALS (A-L), while late memory B cells (LM-B) were also elevated in A-B and fast-progressing ALS (p = 0.0059). Higher M-Tc levels separated A-B from A-L (AUC: 0.887; p < 0.0001). A linear regression model with prespecified clinical independent variables and neurofilament light chain plasma concentration showed that higher frequencies of LM-B predicted a shorter survival (hazard ratio: 1.094, CI: 1.026-1.167; p = 0.006). DISCUSSION: Our data suggest that a systemic elevation of senescent and late memory T and B lymphocytes is a feature of faster progressing ALS and of ALS individuals with bulbar involvement. Lymphocyte senescence and their memory state may be central to the immune dysregulation known to drive disease progression in ALS and a target for biomarkers and therapeutics discovery.

Previous antiplatelet use is associated with hematoma expansion in patients with spontaneous intracerebral hemorrhage.

BACKGROUND: Patients with intracerebral hemorrhage (ICH) often report the use of antiplatelet medications, even more commonly than the use of anticoagulants. The effect of antiplatelet drugs on the course of ICH is controversial. In this study, our aim was to determine the effects of previous antiplatelet therapy on admission hematoma volume and hematoma expansion in patients with spontaneous ICH. METHODS: A consecutive series of patients with a diagnosis of ICH who underwent brain computed tomographic (CT) scans within 12 hours of symptom onset and a follow-up CT scan within 72 hours were included in the study. Hematoma volume was calculated by using the ABC/2 method on admission and follow-up images. Univariate and multivariate analyses were performed to determine the independent role of antiplatelet use on baseline hematoma volume and hematoma expansion (defined as an increase in hematoma volume >12.5 mL or 33% of the baseline ICH volume). RESULTS: A total of 153 patients were included in the study. Fifty-two (34%) patients were using antiplatelet drugs at the time of symptom onset. Antiplatelet users tend to have a larger baseline hematoma volume; however, this difference failed to reach statistical significance (P = .17). Antiplatelet therapy was found to be a significant determinant of substantial hematoma expansion, both in univariate and multivariate analyses (P < .01). CONCLUSIONS: Previous antiplatelet use significantly contributes to hematoma expansion in patients with ICH.

Cerebral venous sinus thrombosis presenting as transient ischemic attacks in a case with homozygous mutations of MTHFR A1298C and CG677T.

We report a case with recurrent, transient attacks of slurred speech, weakness, and numbness of the right half of the face and the right arm without seizure activity, accompanied by headache and double vision. Neurologic examination revealed bilateral papilledema and right abducens palsy. Brain magnetic resonance imaging revealed thrombosis of the dural venous sinuses and the cortical veins, with no evidence of parenchymal lesion. Homozygous mutations were found for methylenetetrahydrofolate reductase (MTHFR) A1298C and MTHFR CG677T. Anticoagulation with heparin and warfarin resulted in prompt cessation of the transient attacks, as well as the signs and symptoms of increased intracranial pressure. This report documents that, although rare, transient ischemic attacks can result from cerebral venous thrombosis.

Multicentre appraisal of amyotrophic lateral sclerosis biofluid biomarkers shows primacy of blood neurofilament light chain.

The routine clinical integration of individualized objective markers of disease activity in those diagnosed with the neurodegenerative disorder amyotrophic lateral sclerosis is a key requirement for therapeutic development. A large, multicentre, clinic-based, longitudinal cohort was used to systematically appraise the leading candidate biofluid biomarkers in the stratification and potential therapeutic assessment of those with amyotrophic lateral sclerosis. Incident patients diagnosed with amyotrophic lateral sclerosis (n = 258), other neurological diseases (n = 80) and healthy control participants (n = 101), were recruited and followed at intervals of 3-6 months for up to 30 months. Cerebrospinal fluid neurofilament light chain and chitotriosidase 1 and blood neurofilament light chain, creatine kinase, ferritin, complement C3 and C4 and C-reactive protein were measured. Blood neurofilament light chain, creatine kinase, serum ferritin, C3 and cerebrospinal fluid neurofilament light chain and chitotriosidase 1 were all significantly elevated in amyotrophic lateral sclerosis patients. First-visit plasma neurofilament light chain level was additionally strongly associated with survival (hazard ratio for one standard deviation increase in log10 plasma neurofilament light chain 2.99, 95% confidence interval 1.65-5.41, P = 0.016) and rate of disability progression, independent of other prognostic factors. A small increase in level was noted within the first 12 months after reported symptom onset (slope 0.031 log10 units per month, 95% confidence interval 0.012-0.049, P = 0.006). Modelling the inclusion of plasma neurofilament light chain as a therapeutic trial outcome measure demonstrated that a significant reduction in sample size and earlier detection of disease-slowing is possible, compared with using the revised Amyotrophic Lateral Sclerosis Functional Rating Scale. This study provides strong evidence that blood neurofilament light chain levels outperform conventional measures of disease activity at the group level. The application of blood neurofilament light chain has the potential to radically reduce the duration and cost of therapeutic trials. It might also offer a first step towards the goal of more personalized objective disease activity monitoring for those living with amyotrophic lateral sclerosis.