Multiple Impairments Research Articles

Clinical judgment versus geriatric assessment for frailty in older patients with cancer

BackgroundGeriatric assessment (GA) is an appropriate method for identifying frailty in older patients with cancer, but a shorter instrument may be easier to use in clinical practice. Clinical judgment is always available and requires no investments in time or resources. The purpose of this study was to assess correlations between clinical judgment for frailty of the cancer specialist, the general practitioner and patient's self-assessment, and the correlation between clinical judgment and GA. MethodsThis was a dual-center inception cohort study of patients with cancer aged ≥70 years starting curative or first-line palliative chemotherapy. GA included the following domains: (instrumental) activities of daily living, nutrition, mobility, cognition, mood, and polypharmacy. Clinical judgment for frailty was rated on a scale from 0 to 10 (0 = not frail, 10 = frail). Correlation was tested using Kendall's tau-b correlation coefficient. ResultsOf all 55 patients, 76% had ≥2 geriatric impairments. Median clinical judgment frailty score was 3 (range 1–10 for cancer specialist and patient and range 0–10 for general practitioner) and did not vary much according to the number of impaired geriatric domains (ranging from 2 for 0–1 impaired domains to 4 for ≥3 impaired domains). Correlations between mutual clinical judgment scores and between clinical judgment and GA were negligible or low. ConclusionCorrelations between clinical judgment scores and between clinical judgment and GA were poor. Most patients with multiple geriatric impairments had low ‘subjective’ frailty scores. Other frailty assessments, such as frailty screening tools or GA, should be considered in addition to clinical judgment when selecting older patients for potential treatment with chemotherapy.

Cognitive impairment and psychological state in acute coronary syndrome patients: A prospective descriptive study at cardiac rehabilitation entry, completion and follow-up.

Cognitive impairment may limit the uptake of secondary prevention in acute coronary syndrome patients, but is poorly understood, including in cardiac rehabilitation participants. The aim of this study was to explore cognitive impairment in relation to psychological state in acute coronary syndrome patients over the course of cardiac rehabilitation and follow-up. Acute coronary syndrome patients without diagnosed dementia were assessed on verbal learning, processing speed, executive function and visual attention, at cardiac rehabilitation entry, completion and follow-up and scores adjusted using normative data. The hospital anxiety and depression scale measured psychological state. Participants (n = 40) had an average age of 66.2 (±8.22) years and were 70% men. Mild cognitive impairment occurred at cardiac rehabilitation entry in single 62.5% and multiple 22.5% domains but was significantly less prevalent by cardiac rehabilitation completion (52.5% and 15.0%) and follow-up (32.5% and 7.0%). Domains most often impaired were verbal learning (52.5%) and processing speed (25.6%), again decreasing significantly with time (verbal learning cardiac rehabilitation completion 42.5%, follow-up 22.5%; processing speed cardiac rehabilitation completion 15.0%, follow-up 15.0%). A small group of patients had persistent multiple domain cognitive impairment. At cardiac rehabilitation entry patients with cognitive impairment in processing speed, a single domain or multiple domains had more depression, and patients with cognitive impairment in executive function had more depression and anxiety. At cardiac rehabilitation entry, mild cognitive impairment is very common in post-acute coronary syndrome patients and worse in patients who have depression or anxiety symptoms. Cognitive impairment decreases significantly by cardiac rehabilitation follow-up. A small proportion of patients has persistent, multiple domain cognitive impairment flagging potential long-term changes and the need for further investigations and cognitive rehabilitation.

Functions necessary for gait independence in patients with stroke: A study using decision tree

BackgroundLittle is known about the existence and impact of interactions among multiple impairments to gait independence. The purpose of this study is to reveal the interaction of physical functions and its impact on gait independence in stroke patients. MethodsThis retrospective study included 108 subacute stroke patients. We conducted a decision tree analysis to examine the existence of interactions in relation to gait independence among the gross motor function of lower limb, knee extension strength, sensory function, and trunk function. Further, we confirmed the existence and impact of interaction detected via the decision tree after adjusting for the effects of confounding factors using logistic regression. ResultsThe knee extension strength and proprioception on the affected side were selected in the first and second level of the decision tree. In addition, the knee extension strength was selected in the third level. The interaction of the knee extension strength and proprioception on the affected side was significantly associated with gait independence, both before and after adjusting for age, visuospatial perception, and cognitive functions. ConclusionsOur results suggest that the interaction of the knee extension strength and proprioception on the affected side is strongly associated with gait independence in stroke patients.

Neuroprotective Effect of Physical Exercise on Neuronal Apoptosis Induced by Tramadol in Cerebral Cortex of Rats

Tramadol is a centrally acting analgesic agent with low affinity for opioid receptors, used for treating moderate to severe pain. Tramadol, like other opioids, induces neuronal apoptosis, which causes multiple neuronal impairments. The current study was conducted to evaluate the potential neuroprotective role of physical exercises on tramadol-induced neuronal apoptosis in the cerebral cortex of rats. Thirty adult male rats were divided into three groups (n= 10) as follow; the control group was gavaged with physiological saline (0.9% NaCl); tramadol group was daily administered with tramadol (40 mg/kg) for 28 days, and physical exercise group was administered with the same dose as tramadol group, then rats were forced to run on the treadmill for 30 min, once a day for 28 days. Tramadol induced histopathological changes in the form of neuroses degeneration and apoptosis. These findings were confirmed by immunohistochemical and blotting studies, which showed upregulation of p53 and downregulation of Bcl-2. In addition, malondialdehyde (MDA), myeloperoxidase (MPO), and nuclear factor kappa B (NF-κB) significantly increased following tramadol administration. At the same time, glutathione (GSH) and glutathione peroxidase (GPx) were decreased. In contrast, physical exercise was found to protect cortical neurons from degeneration and apoptosis produced by tramadol. This was evidenced by the downregulation of p53 and upregulating Bcl-2 expression and the improved changes in the oxidative stress biomarkers in rats. Physical exercise reduced the neuronal apoptosis and degeneration in the cerebral cortex following tramadol administration through suppressing oxidative stress.

SO043MALNUTRITION-INFLAMMATION IS A RISK FACTOR FOR BRAIN ATROPHY RELATIVE COGNITIVE IMPAIRMENT IN MAINTENANCE DIALYSIS PATIENTS

Abstract Background and Aims Cognitive impairment (CI) are prevalent and devastating in dialysis patients, whereas the pathophysiology is not very clear. Brain atrophy may involve in the process of CI. To explore the correlation between brain atrophy and cognitive impairment, as well as the risk factors of brain atrophy, we used the voxel based morphometry (VBM) method to evaluate the changes of brain multi-component volume in maintenance dialysis patients, and analyzed it relationship with detailed cognitive function. Method From July 2013 to July 2014, 181 maintenance dialysis patients in our hospital were enrolled for 3.0T MRI examination and cognitive function evaluation. The statistical parameter map (SPM) 8 software package was used for VBM analysis, and the Monte Carlo simulation method (alphasim method) in the functional neural image analysis software package (AFNI) was used for multiple comparison correction at the cluster level to extract the volume of brain multi-component. Cognitive function was evaluated with MMSE, MoCA, Philadelphia word learning test, Boston Naming Test, semantic fluency test and trial making test. The risk factors for brain volume were explored, and the correlation between brain volume and CI was investigated by regression analysis. Results This study enrolled 181 dialysis patients, including 119 cases of maintenance hemodialysis and 62 cases of peritoneal dialysis. According to MMSE and MoCA, the incidence of cognitive impairment was 22.7% and 66.3% respectively. The mean values gray matter volume and white matter volume were 575.4mm3 and 457.8mm3, respectively. The volume of gray matter, white matter, amygdala, caudate nucleus and hippocampus were positively correlated with the scores of specific cognitive functions such as total, memory, language and execution. Among them, amygdala volume atrophy was significantly related to the decrease of cognitive function such as MMSE (β = 2.81, P = 0.005), MoCA (β = 6.26, P < 0.001). Serum albumin is the risk factor of gray matter volume (β = 5.0, 95% CI = 3.1 to 6.9, P < 0.001) and white matter volume (β = 3.6, 95% CI = 1.7 to 5.5, P < 0.001); Serum Hypersensitive C-reactive protein is the risk factor of gray matter volume (β = -0.9, 95% CI = -1.7 to - 0.1, P = 0.037). Conclusion Brain atrophy in maintenance dialysis patients is closely related to multiple cognitive impairment, and malnutrition - microinflammation may be a risk factor for multi-component brain atrophy.

P1486CHRONIC DIALYSIS IN ELDERLY PATIENTS: FUNCTIONAL PERFORMANCE STATUS AND TREATMENT OUTCOMES - A SINGLE-CENTER STUDY

Abstract Background and Aims The presence of multiple comorbid conditions and different geriatric impairments in elderly patients leads to a certain specificity in the management of this cohort of patients. The aim was to assess changes in functional performance status and treatment outcomes in elderly patients on chronic dialysis. Method A single-center longitudinal prospective study was conducted, which included 48 patients aged 65 years and older who underwent dialysis (hemodialysis and continuous ambulatory peritoneal dialysis) for more than 3 months. Participants’ functional performance status was measured by the Frailty Scale of Rockwood (FSR) at baseline and after a year of treatment. Functional performance status decline was defined as deterioration by 1 or more positions on the FSR, stable was defined as no difference between baseline and follow-up, and improvement was defined as a gain of 1 or more positions. At baseline, all participants were assessed by the Charlson Comorbidity Index (CCI) and standard lab tests were carried out. All data are presented as median and quartiles (25%; 75%). Results The median of age was 69 (67; 74) and 39.6% were women. The main causes of end-stage renal disease were hypertension (33.3%) and diabetes (31.3%). There were 83.3% hemodialysis patients and 31.3% received dialysis up to 1 year. At baseline 16.7% of patients were frail, 54.2% - pre-frail and 29.1% were fit. Among frail patients at the 1-year follow-up, 62.5% died, 12.5% had received a kidney transplant (KT), 25% showed a further functional performance status decline. Among pre-frail patients, almost half (46.2%) experienced functional decline and 15.4% died; the functional status remained unchanged in 30.8% of patients and 3.8% was transplanted; 1 patient (3.8%) had an improvement in functional performance status. Among fit patients, over half (57.2%) showed stable functional status, a functional decline was observed in 21.4% of patients (all of them became frail), 7.1% died and 14.3% had received a KT. All patients, who had stable functional performance status after a year of treatment, had target values of kt/v, albumin, and phosphorus at baseline. All deceased patients (20.8%) had CCI ≥ 6, 60% of them had high serum phosphorus level. Most functional performance status decline among participants was associated with a loss of mobility, which was most often caused by the progression of chronic heart failure (both independently and after heart attack) or chronic arterial failure (diabetic, due to obliterating atherosclerosis of the lower extremities), including the development of critical limb ischemia, especially in patients on hemodialysis. The distribution of patients according to the FSR in the initial assessment and re-assessment are presented in the table below. Conclusion Functional decline is highly prevalent in elderly patients on chronic dialysis, the risk is higher among frail and pre-frail patients. In most cases, functional performance status decline is associated with a loss of mobility due to the progression of chronic heart or arterial failure. Death probability is higher among frail patients and those with high serum phosphorus level (because of inadequate dialysis due to the initially severe condition of these patients) and high CCI. Achievement in the complex of the target values of kt/v, serum albumin, and phosphorus levels can help to maintain the functional status stable.

AB0611 STRAIN ANALYSIS OF THE RIGHT VENTRICLE USING 2D-SPECKLE TRACKING ECHOCARDIOGRAPHY IN A COHORT OF PATIENTS WITH SYSTEMIC SCLEROSIS

Background:Systemic Sclerosis (SSc) is a rare and life-threatening connective tissue disease with multiple organ impairment. Cardio-pulmonary involvement is common: pulmonary fibrosis, pulmonary hypertension (PH), and electrical disorders are the most serious complications and causes of increased mortality.Objectives:We evaluated features related with the onset and development of PH in a cohort of SSc patients. We further studied ecocardiographic abnormalities, by means of 2D-speckle tracking echocardiography (STE) with specific reference to the right ventricular strain measure (RV-strain).Methods:We analyzed data from 50 SSc patients (pts) referred to our University-based Rheumatology Centre and SSc Unit from January 2007 to June 2019 (F/M 45/5; lc/dcSSc 45/5; mean age 59.20±14.357 years; mean disease duration 12.08±8.75 years). All pts underwent general and cardio-pulmonary assessment in our Cardio-Rheumatology Clinic. The following parameters were considered: blood exams, in particular inflammation indexes, uric acid test and serum autoantibodies; pulmonary function tests; high resolution scan of the lungs (HRCT); standard electrocardiogram (ECG) and RV-strain measured by 2D-STE. These examinations were performed according to clinical picture and current methodologies. We compared SSc subjects with (10/50) and without (40/50) PH diagnosis during follow-up regardless of treatments.Results:SSc pts with PH didn’t show significant alterations concerning RV-strain if compared with pts without PH (p=0.707). Nevertheless, RV-strain value was modified in relation to TAPSE alterations in all pts but this data correlated with right ventricular dilatation only in PH subjects. Furthermore, interesting significant values about dilatation of right and left atria (p=0.007, p=0.048), dilatation of inferior vena cava (p=0.037) and right ventricle (p=0.023) were observed. Left ventricular hypertrophy (p=0.012) as well as valvular insufficiencies (mitral and aortic) were more frequent in PH group too (p=0.016). These pts showed higher incidence of skin ulcers (p=0.0001), higher values of blood pressure (p=0.004), elevated uric acid levels (p=0,027) and anti-centromere antibodies positivity (p=0.0001).Conclusion:Our research provides further evidence of the prognostic value of echocardiographic findings in SSc subjects, with focus on PH. Population enlargement is ongoing in order to identify more accurate results about RV-strain, considering the efficacy of PH treatments on cardiac contractility. Speckle tracking echocardiography proves to be a sensitive, low-cost, non-invasive and reliable tool to detect early cardiac impairment in Ssc, full of potential future prospects.Disclosure of Interests:None declared

Toll-like receptor 2 (TLR2)-deficiency impairs male mouse recovery from a depression-like state

Major depression is a prevalent, debilitating disease, yet therapeutic interventions for depression are frequently inadequate. Many clinical and pre-clinical studies have demonstrated that depression is associated with aberrant activation of the inflammatory system, raising the possibility that reducing inflammation may provide antidepressant effects. Using the learned helplessness mouse model, we tested if susceptibility or recovery were affected by deficiency in either of two receptors that initiate inflammatory signaling, Toll-like receptor-4 (TLR4) and TLR2, using knockout male mice. TLR4-/- mice displayed a strong resistance to learned helplessness, confirming that blocking inflammatory signaling through TLR4 provides robust protection against this depression-like behavior. Surprisingly, TLR2-/- mice displayed increased susceptibility to learned helplessness, indicating that TLR2-mediated signaling counteracts susceptibility. TLR2-mediated signaling also promotes recovery, as TLR2-/- mice demonstrated a severe impairment in recovery from learned helplessness. That TLR2 actually protects from learned helplessness was further verified by the finding that administration of the TLR2 agonist Pam3CSK4 reduced susceptibility to learned helplessness. Treatment with Pam3CSK4 also reversed chronic restraint stress-induced impaired sociability and impaired learning in the novel object recognition paradigm, demonstrating that TLR2 stimulation can protect from multiple impairments caused by stress. In summary, these results demonstrate that TLR2-mediated signaling provides a counter-signal to oppose deleterious effects of stress that may be related to depression, and indicate that TLR2 and TLR4 act oppositely to balance mood-relevant responses to stress.

A data-driven framework for selecting and validating digital health metrics: use-case in neurological sensorimotor impairments

Digital health metrics promise to advance the understanding of impaired body functions, for example in neurological disorders. However, their clinical integration is challenged by an insufficient validation of the many existing and often abstract metrics. Here, we propose a data-driven framework to select and validate a clinically relevant core set of digital health metrics extracted from a technology-aided assessment. As an exemplary use-case, the framework is applied to the Virtual Peg Insertion Test (VPIT), a technology-aided assessment of upper limb sensorimotor impairments. The framework builds on a use-case-specific pathophysiological motivation of metrics, models demographic confounds, and evaluates the most important clinimetric properties (discriminant validity, structural validity, reliability, measurement error, learning effects). Applied to 77 metrics of the VPIT collected from 120 neurologically intact and 89 affected individuals, the framework allowed selecting 10 clinically relevant core metrics. These assessed the severity of multiple sensorimotor impairments in a valid, reliable, and informative manner. These metrics provided added clinical value by detecting impairments in neurological subjects that did not show any deficits according to conventional scales, and by covering sensorimotor impairments of the arm and hand with a single assessment. The proposed framework provides a transparent, step-by-step selection procedure based on clinically relevant evidence. This creates an interesting alternative to established selection algorithms that optimize mathematical loss functions and are not always intuitive to retrace. This could help addressing the insufficient clinical integration of digital health metrics. For the VPIT, it allowed establishing validated core metrics, paving the way for their integration into neurorehabilitation trials.

DREAMM-2: Single-agent belantamab mafodotin (GSK2857916) in patients with relapsed/refractory multiple myeloma (RRMM) and renal impairment.

8519 Background: Renal impairment, a frequent complication and poor prognostic factor in RRMM, often leads to poor tolerability of standard regimens. We report outcomes in patients with renal impairment receiving single-agent belantamab mafodotin (2.5 or 3.4 mg/kg; B-cell maturation antigen targeting immunoconjugate not renally metabolized) from the DREAMM-2 post-hoc analysis (NCT03525678). Methods: Eligible patients with RRMM had no active renal conditions and adequate renal function (based on albumin/creatinine ratio [<500 mg/g] and eGFR [mL/min/1.73 m2]: normal [≥90], mild impairment [mild, ≥60≤90], moderate impairment [mod, ≥30≤60]). Results: Overall response rates (95% CI) in patients with mild/mod impairment (2.5 mg/kg: 32% [21.4–44.0]; 3.4 mg/kg: 36% [25.6–48.5]) were similar to those in the overall population ( Lancet Oncol.2020). The median duration of response (DoR) was not reached (NR) in 2.5 mg/kg mild/mod subgroup (95% CI estimate: 4.2 months–NR); median DoR was 7.5 months (4.9–NR) in 3.4 mg/kg mild/mod subgroup. Rates of keratopathy and albuminuria were similar regardless of renal function; rates of anemia, pyrexia, and thrombocytopenia were more frequent in patients with impaired renal function (Table). eGFR did not change or changed to normal in most patients. Conclusions: Following treatment with single-agent belantamab mafodotin, patients with mild/mod renal impairment achieved a similar efficacy and safety profile as patients with normal renal function. Funding: GlaxoSmithKline (205678). Drug linker technology licensed from Seattle Genetics; monoclonal antibody produced using POTELLIGENT Technology licensed from BioWa. Clinical trial information: NCT03525678 . [Table: see text]

Chronic Kidney Disease-Associated Immune Dysfunctions: Impact of Protein-Bound Uremic Retention Solutes on Immune Cells.

Regardless of the primary disease responsible for kidney failure, patients suffering from chronic kidney disease (CKD) have in common multiple impairments of both the innate and adaptive immune systems, the pathophysiology of which has long remained enigmatic. CKD-associated immune dysfunction includes chronic low-grade activation of monocytes and neutrophils, which induces endothelial damage and increases cardiovascular risk. Although innate immune effectors are activated during CKD, their anti-bacterial capacity is impaired, leading to increased susceptibility to extracellular bacterial infections. Finally, CKD patients are also characterized by profound alterations of cellular and humoral adaptive immune responses, which account for an increased risk for malignancies and viral infections. This review summarizes the recent emerging data that link the pathophysiology of CKD-associated immune dysfunctions with the accumulation of microbiota-derived metabolites, including indoxyl sulfate and p-cresyl sulfate, the two best characterized protein-bound uremic retention solutes.

Impaired glucose control is associated with multiple cardiovascular impairments.

Impairments in several markers of the cardiovascular system have been described in impaired glucose tolerance (IGT) and diabetes, but the relative importance of those is not known. We aimed to investigate which cardiovascular markers were most closely linked to an impaired glucose control. In a population-based study of individuals all aged 50years, the Prospective study of Obesity, Energy and Metabolism (POEM), 502 subjects were thoroughly investigated regarding endothelial function, arterial compliance, heart rate variability, arterial blood flow and atherosclerosis, performance at an exercise test with gas exchange (VO2 and VCO2 ), left ventricular structure and function, lung function and multiple measurements of blood pressure. Based on an oral glucose tolerance test (OGTT), the participants were grouped into normal, IGT and diabetes. Of all haemodynamic and structural variables analysed, an impaired glucose control was most closely related to resting heart rate (based on chi-square value at ANOVA). Heart rate was followed by maximal workload, VO2 recovery 5min following exercise, reflectance index at pulse wave analysis, manual systolic blood pressure, ambulatory pulse and pulse pressure, echogenicity of carotid intima-media complex at ultrasound, and pulse wave velocity (p<.0005 for all variables). All of these variables still showed p<.05 versus an impaired glucose control following adjustment for BMI. Of multiple measured cardiovascular markers, resting heart rate was most closely related to an impaired glucose control. Also exercise capacity and the recovery in VO2 following exercise were amongst the top-ranked cardiovascular impairments linked to an impaired glucose control.

Resting-state hyperconnectivity within the default mode network impedes the ability to initiate cognitive performance in first-episode schizophrenia patients

Among multiple cognitive impairments present in schizophrenia, a decline in fast information processing is one of the most severe neuropsychological deficit. Reduced ability to efficiently launch a coherent cognitive activity might be a significant factor contributing to poor results in time-limited tasks obtained by schizophrenia patients. The aim of this study was to identify neurophysiological predictors of expected cognitive initiation failures in a group of first-episode schizophrenia individuals (SZ).To evaluate the effectiveness of initiation, a dynamic analysis of design fluency test was applied, assessing to what extent the productivity was focused within the first interval of the performance, what is a typical way healthy subjects execute this task. Resting-state EEG recordings were obtained from SZ patients (n = 34) and controls (n = 30) to examine functional connectivity between 84 intra-cortical current sources determined by eLORETA (exact low-resolution brain electromagnetic tomography) for six conventionally analyzed frequencies. The nonparametric randomization approach was used to identify hypo- and hyper-connections, i.e. synchronizations significantly differentiating the studied samples in terms of connectivity strength.Generally, SZ patients obtained poor outcomes in fluency test and dynamic analysis of performance confirmed the presence of initiation deficit in clinical sample, which was a single factor explaining the intergroup difference regarding the entire task. In the majority of frequencies, the arrangement of synchronizations in SZ group was dominated by hypo-connections, except for the theta band, in which the strength of synchronizations between posterior cingulate cortex, cuneus and precuneus was significantly higher for SZ group. These theta-band hyper-connections turned out to be significant predictors of cognitive initiation failure in the clinical sample. Additionally, theta hyper-connections correlated negatively with the total number of unique designs generated by patients, however, the strength of this correlation was weaker than regarding initiation index.The results of this study suggest that baseline hyperconnectivity within the posterior hub of the Default Mode Network, containing posterior cingulate gyrus and precuneus, might disturb effective cognitive outcome, not only by interfering with task-positive functional networks but also by delaying the starting phase of performance, which might be specifically deleterious for the execution of time-limited tests.

Cognitive Correlates of Early Life Abuse in Adolescent Psychiatric Inpatients

Childhood abuse leads to multiple neurobiological consequences, including altered patterns of inflammatory response. In adults with childhood abuse, there have been reports of multiple cognitive impairments, even in the absence of psychiatric diagnoses. In this study we examined cognitive impairments associated with three different forms of abuse in adolescent psychiatric inpatients.

Sensitivity of the Inhomogeneous Magnetization Transfer Imaging Technique to Spinal Cord Damage in Multiple Sclerosis.

The inhomogeneous magnetization transfer technique has demonstrated high specificity for myelin, and has shown sensitivity to multiple sclerosis-related impairment in brain tissue. Our aim was to investigate its sensitivity to spinal cord impairment in MS relative to more established MR imaging techniques (volumetry, magnetization transfer, DTI). Anatomic images covering the cervical spinal cord from the C1 to C6 levels and DTI, magnetization transfer/inhomogeneous magnetization transfer images at the C2/C5 levels were acquired in 19 patients with MS and 19 paired healthy controls. Anatomic images were segmented in spinal cord GM and WM, both manually and using the AMU40 atlases. MS lesions were manually delineated. MR metrics were analyzed within normal-appearing and lesion regions in anterolateral and posterolateral WM and compared using Wilcoxon rank tests and z scores. Correlations between MR metrics and clinical scores in patients with MS were evaluated using the Spearman rank correlation. AMU40-based C1-to-C6 GM/WM automatic segmentations in patients with MS were evaluated relative to manual delineation. Mean Dice coefficients were 0.75/0.89, respectively. All MR metrics (WM/GM cross-sectional areas, normal-appearing and lesion diffusivities, and magnetization transfer/inhomogeneous magnetization transfer ratios) were observed altered in patients compared with controls (P < .05). Additionally, the absolute inhomogeneous magnetization transfer ratio z scores were significantly higher than those of the other MR metrics (P < .0001), suggesting a higher inhomogeneous magnetization transfer sensitivity toward spinal cord impairment in MS. Significant correlations with the Expanded Disability Status Scale (ρ = -0.73/P = .02, ρ = -0.81/P = .004) and the total Medical Research Council scale (ρ = 0.80/P = .009, ρ = -0.74/P = .02) were observed for inhomogeneous magnetization transfer and magnetization transfer ratio z scores, respectively, in normal-appearing WM regions, while weaker and nonsignificant correlations were obtained for DTI metrics. With inhomogeneous magnetization transfer being highly sensitive to spinal cord damage in MS compared with conventional magnetization transfer and DTI, it could generate great clinical interest for longitudinal follow-up and potential remyelinating clinical trials. In line with other advanced myelin techniques with which it could be compared, it opens perspectives for multicentric investigations.

Preliminary Findings on Self-Reported Voice Disorders in Urban Ghana: A Qualitative Description Study

This preliminary qualitative description study explored knowledge from urban Ghanaians about the nature and impact of their self-reported voice problem. Ten Ghanaians were screened for a self-reported voice disorder using the Voice Handicap Index–10 (VHI-10), and they also completed a structured interview with a speech-language therapist. Content analysis was completed from interview responses using quantification of data. Four out of 10 adult Ghanaians demonstrated high VHI-10 scores that indicated a self-reported voice disorder. Themes that emerged included a recurring problem with voice, multiple vocal impairments, limitations with participating in vocal activities, and other health problems. Lack of financial resources and little knowledge about voice disorders were barriers to accessing care. In summary, four adult Ghanaians with a self-reported voice disorder described multiple problems with their voice, limiting their participation in vocal activities. Implications of these preliminary findings include early identification and improving voice care access to avoid handicapping voice problems.

Dual-Targeted Autoimmune Sword in Fatal Epilepsy: Patient's glutamate receptor AMPA GluR3B peptide autoimmune antibodies bind, induce Reactive Oxygen Species (ROS) in, and kill both human neural cells and T cells

Nodding Syndrome (NS) is a fatal pediatric epilepsy of unknown etiology, accompanied by multiple neurological impairments, and associated with Onchocerca volvulus (Ov), malnutrition, war-induced trauma, and other insults. NS patients have neuroinflammation, and ~50% have cross-reactive Ov/Leiomodin-1 neurotoxic autoimmune antibodies. ResultsStudying 30 South Sudanese NS patients and a similar number of healthy subjects from the same geographical region, revealed autoimmune antibodies to 3 extracellular peptides of ionotropic glutamate receptors in NS patients: AMPA-GluR3B peptide antibodies (86%), NMDA-NR1 peptide antibodies (77%) and NMDA-NR2 peptide antibodies (87%) (in either 1:10, 1:100 or 1:1000 serum dilution). In contrast, NS patients did not have 26 other well-known autoantibodies that target the nervous system in several autoimmune-mediated neurological diseases. We demonstrated high expression of both AMPA-GluR3 and NMDA-NR1 in human neural cells, and also in normal human CD3+ T cells of both helper CD4+ and cytotoxic CD8+ types. Patient's GluR3B peptide antibodies were affinity-purified, and by themselves precipitated short 70 kDa neuronal GluR3. NS patient's affinity-purified GluR3B peptide antibodies also bound to, induced Reactive Oxygen Species (ROS) in, and killed both human neural cells and T cells within 1-2 hours only. NS patient's purified IgGs, or serum (1:10 or 1:30), induced similar effects. In vivo video EEG experiments in normal mice, revealed that when NS patient's purified IgGs were released continuously (24/7 for 1 week) in normal mouse brain, they induced all the following: 1.Seizures, 2. Cerebellar Purkinje cell loss, 3. Degeneration in the hippocampus and cerebral cortex, and 4. Elevation of CD3+ T cells, and of activated Mac-2+microglia and GFAP+astrocytes in both the gray and white matter of the cerebral cortex, hippocampus, corpus calossum and cerebellum of mice. NS patient's serum cytokines: IL-1β, IL-2, IL-6, IL-8, TNFα, IFNγ, are reduced by 85–99% compared to healthy subjects, suggesting severe immunodeficiency in NS patients. This suspected immunodeficiency could be caused by combined effects of the: 1. Chronic Ov infection, 2. Malnutrition, 3. Killing of NS patient's T cells by patient's own GluR3B peptide autoimmune antibodies (alike the killing of normal human T cells by the NS patient's GluR3B peptide antibodies found herein in vitro). ConclusionsRegardless of NS etiology, NS patients suffer from ‘Dual-targeted Autoimmune Sword’: autoimmune AMPA GluR3B peptide antibodies that bind, induce ROS in, and kill both neural cells and T cells. These neurotoxic and immunotoxic GluR3B peptide autoimmune antibodies, and also NS patient's NMDA-NR1/NR2A and Ov/Leiomodin-1 autoimmune antibodies, must be silenced or removed. Moreover, the findings of this study are relevant not only to NS, but also to many more patients with other types of epilepsy, which have GluR3B peptide antibodies in serum and/or CSF. This claim is based on the following facts: 1. The GluR3 subunit is expressed in neural cells in crucial brains regions, in motor neurons in the spinal cord, and also in other cells in the body, among them T cells of the immune system, 2. The GluR3 subunit has diverse neurophysiological role, and its deletion or abnormal function can: disrupt oscillatory networks of both sleep and breathing, impair motor coordination and exploratory activity, and increase the susceptibility to generate seizures, 3. GluR3B peptide antibodies were found so far in ~27% of >300 epilepsy patients worldwide, which suffer from various other types of severe, intractable and enigmatic epilepsy, and which turned out to be 'Autoimmune Epilepsy'. Furthermore, the findings of this study could be relevant to different neurological diseases besides epilepsy, since other neurotransmitter-receptors autoantibodies are present in other neurological and psychiatric diseases, e.g. autoimmune antibodies against other GluRs, Dopamine receptors, GABA receptors, Acetylcholine receptors and others. These neurotransmitter-receptors autoimmune autoantibodies might also act as ‘Dual-targeted Autoimmune Sword’ and damage both neural cells and T cells (as the AMPA-GluR3B peptide antibodies induced in the present study), since T cells, alike neural cells, express most if not all these neurotransmitter receptors, and respond functionally to the respective neurotransmitters - a scientific and clinical topic we coined 'Nerve-Driven Immunity'.

Health profile of older adults assisted by the Elderly Caregiver Program of Health Care Network of the City of São Paulo.

ABSTRACTObjective To assess the health profile of community-dwelling older adults, according to sex, assisted by the Elderly Caregiver Program of the City of São Paulo.Methods Secondary data of 535 older adults, assisted by ten Elderly Caregiver Program teams from the southern region of São Paulo, were collected from medical records and the Multidimensional Evaluation of Older People in Primary Care, after verifying the inclusion and exclusion criteria for the study and obtaining subjects’ consent.Results Older adults assisted by this program were predominantly female (77.6%), mean age of 76.2±8.0 years. They had negative self-rated health (67.8%), difficulties in instrumental activities of daily living (68.4%) and signs of mood changes (60.3%). A high prevalence of older adults with vision problems (58.8%), polypharmacy (58.1%), memory-related complaints (55.8%) and multiple morbidities (50.6%) were observed. The prevalence of multiple morbidities, polypharmacy, cognitive impairment and signs of mood changes were higher in women. On the other hand, men reported more hearing problems than women.Conclusion The poorer health conditions of the older adults in this study, evidenced by a high prevalence of subjects with negative self-rated health, difficulties in instrumental activities of daily living, multiple morbidities, polypharmacy and other complaints (sensorial changes, depressive and cognitive symptoms), reinforce the importance of this program as a long-term care policy and as a way to ensure these older adults can continue living in their communities.

Clinical Examination and Self-Reported Upper Extremity Impairments in Patients with Long-Standing Type 1 Diabetes Mellitus.

Aim The aims of the current study were (1) to determine the prevalence of upper extremity impairments (UEIs) in patients with type 1 diabetes by clinical investigation; (2) to investigate if self-reported impairments were concordant with clinical findings and if key questions could be identified; and (3) to investigate if answers to our self-reported questionnaire regarding UEIs are reliable. Methods Patients with type 1 diabetes were invited to participate in a cross-sectional study of clinical and self-reported (12 items) UEIs in adjunction to ordinary scheduled clinical visit. Before the visit, a questionnaire on UEIs was filled in twice (test-retest) followed by clinical testing at the planned visit. Results In total, 69 patients aged 45 ± 14 years and with diabetes duration 26 ± 15 were included in the study. In the clinical examination, two-thirds (65%) of the patients showed one or more UEI, with failure to perform hand against back as the most common clinical finding (40%) followed by positive Phalen's test (27%), Tinel's test (26%), and Prayer's sign (24%). UEIs observed by clinical examination were often bilateral, and multiple impairments often coexisted. Self-reported shoulder stiffness was associated with impaired shoulder mobility and with Prayer's sign. Self-reported reduced hand strength was associated to lower grip force, Prayer's sign, trigger finger, fibrosis string structures, and reduced thenar strength as well as reduced shoulder mobility. In addition, self-reporting previous surgery of carpal tunnel and trigger finger was associated with several clinical UEIs including shoulder, hand, and finger. The test-retest of the questionnaire showed a high agreement of 80-98% for reported shoulder, hand, and finger impairments. Conclusion UEIs are common in type 1 diabetes. Self-reported shoulder stiffness and reduced hand strength might be used to capture patients with UEIs in need of clinical investigation and enhanced preventive and therapeutic strategies, as well as rehabilitative interventions.

Performance of quick sequential organ failure assessment (qSOFA) score for prognosis of heat-related hospitalized patients

BackgroundHeat-related illnesses pose significant threats to human health. Objectives(1) To evaluate the use of qSOFA score for prognosis of heat-related hospitalized patients; and (2) identify other predictors for patient prognosis. MethodsUsing 28-day mortality as the primary endpoint, a retrospective, observational study of patients hospitalized between June 2013 and September 2018 was conducted. ResultsThe qSOFA score from 84 patients was identified as an independent predictor of patient prognosis. The area under the receiver operating characteristic curves for qSOFA score was 0.702, and a sensitivity of 100.00% and a specificity of 47.06% were found for qSOFA score greater than or equal to 2. Other predictors included bilirubin, urea nitrogen, and troponin I levels. ConclusionsqSOFA score can be used as a parameter to distinguish patients with severe heat-related illness prior to further clinical analyses. In addition to that, multiple organ impairment should be considered when assessing patient prognosis.