A case of hemophagocytic lymphohistiocytosis caused by an Epstein-Barr virus infection, presenting with unremitting fever and rash

Hemophagocytic lymphohistiocytosis (HLH) is a hyperinflammatory syndrome caused by excessive activation of lymphocytes and macrophages, leading to cytokine storm. Infection-associated HLH is most common, and Epstein-Barr virus is the leading triggers. Quick diagnosis is essential for starting the treatment before irreversible damage. We report a case of 16-year-old boy who presented with unremitted fever, jaundice, and erythematous maculopapular rash all over the body. Investigations showed thrombocytopenia, hyperferritinemia, hypertriglycemia, and the bone marrow biopsy showed hemophagocytosis. Epstein-Barr virus antibody was positive. He responded to chemotherapy as per the HLH-2004 protocol and supportive treatment, and was discharged without complication on day 17

Clinical Characteristics of Involuntary Movement in Hospitalized Patients

Objective Neurological symptoms in hospitalized patients are not rare, and neurological consultation for movement disorders is especially important in evaluating or managing those with various movement disorders. Therefore, we investigated a clinical pattern of in-hospital consultations for various movement disorders in a tertiary care university hospital. Methods Over two years, a total of 202 patients (70.7 ± 11.8 years of age) presenting with movement disorders referred to movement disorder specialists were investigated. Results The main symptoms referred by nonneurologists were tremor (56.9%), parkinsonism (16.8%), and gait disturbance (8.9%). The most frequent diagnostic category was toxic/metabolic-caused movement disorder (T/MCMD) (35%) with regard to medications, followed by Parkinson’s disease (PD) (16%). Regarding the mode of onset, T/MCMD was the leading cause for acute (68%) and subacute onset (46%), while PD was the leading disorder (31%) for chronic onset. Conclusion The current study showed a characteristic pattern of inpatients presenting with movement disorders. Furthermore, our findings highlighted the clinical significance of drug use or metabolic problems for treating this patient population

Toll-Like Receptor 4 Decoy, TOY, Attenuates Gram-Negative Bacterial Sepsis

Lipopolysaccharide (LPS), the Gram-negative bacterial outer membrane glycolipid, induces sepsis through its interaction with myeloid differentiation protein-2 (MD-2) and Toll-like receptor 4 (TLR4). To block interaction between LPS/MD-2 complex and TLR4, we designed and generated soluble fusion proteins capable of binding MD-2, dubbed TLR4 decoy receptor (TOY) using ‘the Hybrid leucine-rich repeats (LRR) technique’. TOY contains the MD-2 binding ectodomain of TLR4, the LRR motif of hagfish variable lymphocyte receptor (VLR), and the Fc domain of IgG1 to make it soluble, productive, and functional. TOY exhibited strong binding to MD-2, but not to the extracellular matrix (ECM), resulting in a favorable pharmacokinetic profile in vivo. TOY significantly extended the lifespan, when administered in either preventive or therapeutic manners, in both the LPS- and cecal ligation/puncture-induced sepsis models in mice. TOY markedly attenuated LPS-triggered NF-κB activation, secretion of proinflammatory cytokines, and thrombus formation in multiple organs. Taken together, the targeting strategy for sequestration of LPS/MD-2 complex using the decoy receptor TOY is effective in treating LPS- and bacteria-induced sepsis; furthermore, the strategy used in TOY development can be applied to the generation of other novel decoy receptor proteins

Fasting glucose variability and risk of dementia in Parkinson’s disease: a 9-year longitudinal follow-up study of a nationwide cohort

BackgroundDiabetes is associated with an increased risk of Parkinson’s disease dementia (PDD); however, it is unknown whether this association is dependent on continuous hyperglycemia, hypoglycemic events, or glycemic variability. We aimed to investigate the relationship between visit-to-visit fasting glucose variability and PDD development in patients with Parkinson’s disease (PD).MethodsUsing data from the Korean National Health Insurance Service, we examined 9,264 patients aged ≥40 years with de novo Parkinson’s disease (PD) who underwent ≥3 health examinations and were followed up until December 2019. Glucose variability was measured using the coefficient of variation, variability independent of the mean, and average real variability. Fine and Gray competing regression analysis was performed to determine the effect of glucose variability on incident PDD.ResultsDuring the 9.5-year follow-up period, 1,757 of 9,264 (19.0%) patients developed PDD. Patients with a higher visit-to-visit glucose variability had a higher risk of future PDD. In the multivariable adjusted model, patients with PD in the highest quartile (subdistribution hazard ratio [SHR] = 1.50, 95% CI 1.19 to 1.88), quartile 3 (SHR = 1.29, 95% CI 1.02 to 1.62), and quartile 2 (SHR = 1.30, 95% CI 1.04 to 1.63) were independently associated with a higher risk of PDD than those in the lowest quartile.ConclusionWe highlighted the effect of long-term glucose variability on the development of PDD in patients with PD. Furthermore, our findings suggest that preventive measures for constant glucose control may be necessary to prevent PDD

Independent effect of body mass index variation on amyloid-β positivity

ObjectivesThe relationship of body mass index (BMI) changes and variability with amyloid-β (Aβ) deposition remained unclear, although there were growing evidence that BMI is associated with the risk of developing cognitive impairment or AD dementia. To determine whether BMI changes and BMI variability affected Aβ positivity, we investigated the association of BMI changes and BMI variability with Aβ positivity, as assessed by PET in a non-demented population.MethodsWe retrospectively recruited 1,035 non-demented participants ≥50 years of age who underwent Aβ PET and had at least three BMI measurements in the memory clinic at Samsung Medical Center. To investigate the association between BMI change and variability with Aβ deposition, we performed multivariable logistic regression. Further distinctive underlying features of BMI subgroups were examined by employing a cluster analysis model.ResultsDecreased (odds ratio [OR] = 1.68, 95% confidence interval [CI] 1.16–2.42) or increased BMI (OR = 1.60, 95% CI 1.11–2.32) was associated with a greater risk of Aβ positivity after controlling for age, sex, APOE e4 genotype, years of education, hypertension, diabetes, baseline BMI, and BMI variability. A greater BMI variability (OR = 1.73, 95% CI 1.07–2.80) was associated with a greater risk of Aβ positivity after controlling for age, sex, APOE e4 genotype, years of education, hypertension, diabetes, baseline BMI, and BMI change. We also identified BMI subgroups showing a greater risk of Aβ positivity.ConclusionOur findings suggest that participants with BMI change, especially those with greater BMI variability, are more vulnerable to Aβ deposition regardless of baseline BMI. Furthermore, our results may contribute to the design of strategies to prevent Aβ deposition with respect to weight control