The Impact of Systemic Inflammation on Alzheimer’s Disease Pathology

Alzheimer’s disease (AD) is a devastating age-related neurodegenerative disorder with an alarming increasing prevalence. Except for the recently FDA-approved Aducanumab of which the therapeutic effect is not yet conclusively proven, only symptomatic medication that is effective for some AD patients is available. In order to be able to design more rational and effective treatments, our understanding of the mechanisms behind the pathogenesis and progression of AD urgently needs to be improved. Over the last years, it became increasingly clear that peripheral inflammation is one of the detrimental factors that can contribute to the disease. Here, we discuss the current understanding of how systemic and intestinal (referred to as the gut-brain axis) inflammatory processes may affect brain pathology, with a specific focus on AD. Moreover, we give a comprehensive overview of the different preclinical as well as clinical studies that link peripheral Inflammation to AD initiation and progression. Altogether, this review broadens our understanding of the mechanisms behind AD pathology and may help in the rational design of further research aiming to identify novel therapeutic targets.

Antioxidant and immunomodulatory effect of AKSS16-LIV01 – a multi herbal formulation against ethanol induced liver dysfunction in mice

Background Liver complication arises commonly due to high alcohol consumption rate. Majority of the people residing in both developed and under developed countries consuming alcohol face various liver complications such as liver fibrosis, fatty liver, liver cirrhosis and even hepatocellular carcinoma. Invention of safe and symptomatic medication to overcome this situation is a new challenge worldwide. The main objective of the study is to deliver a safe and symptomatic medication to reduce the ethanol induced liver dysfunction. Methods In this study we have developed a multi herbal formulation (AKSS-16-LIV01) which minimised liver damage against various toxicants. Swiss albino mice were divided into seven groups where ethanol induced damage was observed for weeks followed by sanative response observation by our herbal formulation. The groups are normal control group, ethanol treated group (50% v/v), AKSS16-LIV01 low dose (75 mg/kg/day) pre-treated group, AKSS16-LIV01 middle dose (150 mg/kg/day) pre-treated group, AKSS16-LIV01 high dose (300 mg/kg/day) pre-treated group, Sylimarin pre-treated group (100 mg/kg/day) and only AKSS16-LIV01 (300 mg/kg/day) treated group. Results The results potrayed significant elevation of various biochemical parameters, lipid profile parameters, lipid peroxidation, nitric oxide (NO) concentration, nitric oxide synthase level and pro inflammatory cytokines level i.e. tumor necrosis factor (TNF-α) and transforming growth factor (TGF-β1) in the ethanol induced mice. On the other hand serum total protein, total albumin, albumin globulin ratio and level of tissue antioxidant enzymes activity (SOD, CAT, GSH and GPx) were significantly reduced by ethanol. Dose depended therapeutic application of the formulation (AKSS16-LIV01) significantly suppressed all the relevant above parameters and protected the liver from ethanol induced fibrogenesis. Apart from this gross morphology of the liver, H&E liver histology and massontrichrome&serius red examination of the liver section strongly supported the hepatoprotive effect of the formulation as compared with standard drug Sylimarin. Result of the study implies that developed multi herbal formulation (AKSS16-LIV01) at a dose of 300 mg/kg/day gave the best optimum response to reduce the ethanol intoxication. Conclusion Result clearly depict that AKSS16-LIV01 may be a safe and nontoxic medication which protect the liver against ethanol induced oxidative injury and maintained pro inflammatory cytokines level in the future. Graphical Abstract

Cost-Effectiveness Analysis of Immunotherapy in Patient with Allergic Rhinitis

Background and Objectives All treatments must be effective and affordable. Although it is clear that immunotherapy is effective in patients with allergic rhinitis, no cost-effectiveness analysis has been conducted in Korea.Subjects and Method We compared 10 years of total treatment costs (medical expense+ transportation cost+time cost) with medications and symptoms scores assuming that adult patients with allergic rhinitis are treated only with symptomatic medication (medication model) or immunotherapy (subcutaneous or sublingual) plus symptomatic medication [subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT) models, respectively]. For cost-effectiveness analysis, related papers and domestic medical statistics were used.Results The total treatment costs for the first 3 years were ₩3330199, ₩6605557, and ₩7130467 for the Medication model, SCIT model and SLIT model, respectively. The total treatment costs for the 10-year period were ₩7996087, ₩8588624, and ₩9113534 for the medication model, SCIT model, and SCIT model, respectively. The cumulative symptoms plus medications scores decreased 0.44 times in both immunotherapy models compared to the medication model. Conclusion The initial cost of immunotherapy is more expensive than symptomatic medication, but the total cost for 10 years is similar. In addition, immunotherapy can reduce symptoms by more than half. Therefore, it is a cost-effective treatment for allergic rhinitis.

Gastric adenocarcinoma advanced ina final year student. A case report

Gastric carcinoma is most common in the 50-70 age group [2], and is extremely rareunder the age of 30; grows rapidly andsteadily to reach higher levels in older agegroups [3]. Basically, there are two sub-types of adenocarcinoma arising from thegastric mucosa: intestinal and diffusebased on Lauren (1965) criteria. The disease was fatigue, with dysphagia associated with solid food, with anorexia, and with weight loss; (about 10 kg for the last 3 months). During this period, he rece-ived symptomatic medication but without any medical visit.Clinical examination revealed a pale skin, with decreased turgor, and in the abdomen was found a tangible mass in the abdomen, easily sensible, other quadrats of the abdo-men loose… Conclusion: Whenever symptoms of dys-phagia, loss of appetite and hematemesis appear, and further investigations should be made, as early diagnosis of a gastric tumor in this group plays a crucial role in determining the prognosis.

The burden attributable to headache disorders in children and adolescents in Lithuania: estimates from a national schools-based study

Background We recently showed headache to be common in children (aged 7–11 years) and adolescents (aged 12–17) in Lithuania. Here we provide evidence from the same study of the headache-attributable burden. Methods Following the generic protocol for Lifting The Burden’s global schools-based study, this cross-sectional survey administered self-completed structured questionnaires to pupils within classes in 24 nationally representative schools selected from seven regions of the country. Headache diagnostic questions were based on ICHD-3 beta criteria but for the inclusion of undifferentiated headache (UdH; defined as mild headache with usual duration < 1 h). Burden enquiry was conducted in multiple domains. Results Questionnaires were completed by 2505 pupils (1382 children, 1123 adolescents; participating proportion 67.4%), of whom 1858 reported headache in the preceding year, with mean frequency (±SD) of 3.7 ± 4.5 days/4 weeks and mean duration of 1.6 ± 1.9 h. Mean proportion of time in ictal state, estimated from these, was 0.9% (migraine 1.5%, probable medication-overuse headache [pMOH] 10.9%). Mean intensity on a scale of 1–3 was 1.6 ± 0.6 (mild-to-moderate). Symptomatic medication was consumed on 1.5 ± 2.8 days/4 weeks. Lost school time was 0.5 ± 1.5 days/4 weeks (migraine 0.7 ± 1.5, pMOH 5.0 ± 7.8) based on recall, but about 50% higher for migraine according to actual absences recorded in association with reported headache on the preceding day. More days were reported with limited activity (overall 1.2 ± 2.4, migraine 1.5 ± 2.2, pMOH 8.4 ± 8.5) than lost from school. One in 30 parents (3.3%) missed work at least once in 4 weeks because of their son’s or daughter’s headache. Emotional impact and quality-of-life scores generally reflected other measures of burden, with pMOH causing greatest detriments, followed by migraine and tension-type headache, and UdH least. Burdens were greater in adolescents than children as UdH differentiated into adult headache types. Conclusions Headache in children and adolescents in Lithuania is mostly associated with modest symptom burden. However, the consequential burdens, in particular lost school days, are far from negligible for migraine (which is prevalent) and very heavy for pMOH (which, while uncommon in children, becomes four-fold more prevalent in adolescents). These findings are of importance to both health and educational policies in Lithuania.

Improved gastrointestinal profile with diroximel fumarate is associated with a positive impact on quality of life compared with dimethyl fumarate: results from the randomized, double-blind, phase III EVOLVE-MS-2 study

Background: Diroximel fumarate (DRF) is a novel oral fumarate approved for relapsing forms of multiple sclerosis (MS). DRF demonstrated significantly improved gastrointestinal (GI) tolerability versus dimethyl fumarate (DMF) with fewer days of Individual Gastrointestinal Symptom and Impact Scale (IGISIS) scores ⩾2, GI adverse events (AEs), and treatment discontinuations due to GI AEs. Our aim was to evaluate the impact of GI tolerability events on quality of life (QoL) for patients with relapsing–remitting MS who received DRF or DMF in EVOLVE-MS-2. Methods: A post hoc analysis was conducted in patients who were enrolled in the randomized, blinded, 5-week, EVOLVE-MS-2 [ClinicalTrials.gov identifier: NCT03093324] study of DRF versus DMF. Patients completed daily IGISIS and Global GISIS (GGISIS) eDiary questionnaires to assess GI symptom intensity and interference with daily activities and work. Results: In total, 504 patients (DRF, n = 253; DMF, n = 251) received study drug and 502 (DRF, n = 253; DMF, n = 249) completed at least one post-baseline questionnaire. With DRF, GI symptoms were less likely to interfere ‘quite a bit’ or ‘extremely’ with regular daily activities [IGISIS: DRF, 9.5% (24/253) versus DMF, 28.9% (72/249)] or work productivity [GGISIS: DRF, 6.1% (10/165) versus DMF, 11.3% (18/159)]. DRF-treated patients had fewer days with ⩾1 h of missed work (DRF, 43 days, n = 20 versus DMF, 88 days, n = 26). DMF-treated patients reported highest GI symptom severity and missed work at week 2–3 shortly after completing the titration period, which coincided with the majority of GI-related treatment discontinuations [58.3% (7/12)]. GI tolerability AEs [DRF, 34.8% (88/253); DMF, 48.2% (121/251)], concomitant symptomatic medication use [DRF, 19.3% (17/88) versus DMF, 30.6% (37/121)], and GI-related discontinuations (DRF, 0.8% versus DMF, 4.8%) were lower with DRF versus DMF. Conclusions: The improved GI tolerability with DRF translated into clinically meaningful benefits to QoL, as patients experienced less impact on daily life and work and required less concomitant symptomatic medication use. Trial registration: [ClinicalTrials.gov identifier: NCT03093324]

Triptanophobia in migraine: A case-control study on the causes and consequences of the non-use of triptans in chronic migraine patients.

Background Triptanophobia is the excessive and inadequately justified concern about the potential risks of triptans. In this study we evaluate the possible causes of non-use of triptans in chronic migraine patients and the possible consequences. Results We included 941 patients, 86.2% female with a mean age of 39.9 years. Mean number of headache days per month was 24.1. The number of patients using triptans was 247 (26.2%). Triptans had been discontinued due to adverse events in 116 patients (12.3%), so 578 patients (61.4%) were triptan naïve. Formal contraindications were found in 23 patients (2.4%). Frequency of vascular risk factors, contraceptive use or age did not differ between the groups (p > 0.1). Participants with triptans used symptomatic medication fewer days per month (13.9 vs. 17.1, p < 0.001), had used prior prophylactic treatment more frequently (79.4% vs. 34.8%, p < 0.001) and presented symptomatic medication overuse less frequently (55.1% vs. 63.0%, p = 0.03). Conclusion Triptans were not used in three-quarters of chronic migraine patients. Non-use of triptans was not justified by inadequate tolerability, frequency of formal contraindications or frequency of vascular risk factors. Triptan use was associated with a better clinical situation at the moment of referral to a headache unit.