clinical severity
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2022 ◽  
pp. 1-8
Hande Yüceer ◽  
Duygu Gezen Ak ◽  
Gülçin Benbir Şenel ◽  
Erdinç Dursun ◽  
Vuslat Yılmaz ◽  

Abstract Objective: Narcolepsy is a chronic sleep disorder long hypothesised to be an autoimmune disease. Complement-mediated immune mechanisms have not been investigated in detail in narcolepsy. Our aim was to establish the significance of classical pathway activation in narcolepsy. Methods: Sera of 42 narcolepsy patients and 26 healthy controls were screened with ELISA to determine the levels of C1q, C3a, C4d and complement component 4 binding protein (C4BP). A home-made ELISA method was developed to detect antibodies to C4BP-alpha (anti-C4BPA). The correlation between complement levels and clinical findings was examined. Results: C1q levels were significantly higher in narcolepsy patients while C4d and C4BP levels were significantly lower compared to healthy controls. C3a levels were comparable among patients and controls. Eleven narcolepsy patients showed serum anti-C4BPA levels. Total rapid eye movements (REM) time, sleep onset latency, REM sleep latency, sleep activity, percentage of wakefulness after sleep onset and Epworth sleepiness scale scores were correlated with levels of different complement factors. Conclusion: Complement-mediated immune mechanisms might partake in narcolepsy pathogenesis. The precise role of autoantibodies on complement level alterations needs to be investigated. Levels of complement factors and degradation products may potentially be utilised as biomarkers to predict the clinical severity of narcolepsy.

2022 ◽  
Hannah Hussey ◽  
Mary-Ann Davies ◽  
Alexa Heekes ◽  
Carolyn Williamson ◽  
Ziyaad Valley-Omar ◽  

Background Emerging data suggest that SARS-CoV-2 Omicron variant of concern (VOC)is associated with reduced risk of severe disease. The extent to which this reflects a difference in the inherent virulence of Omicron, or just higher levels of population immunity, is currently not clear. Methods RdRp target delay (RTD: a difference in cycle threshold value of RdRp - E > 3.5) in the Seegene AllplexTM 2019-nCoV PCR assay is a proxy marker for the Delta VOC. The absence of this proxy marker in the transition period was used to identify suspected Omicron VOC infections. Cox regression was performed for the outcome of hospital admission in those who tested positive for SARS-CoV-2 on the Seegene AllplexTM assay from 1 November to 14 December 2021 in the Western Cape Province, South Africa, public sector. Vaccination status at time of diagnosis, as well as prior diagnosed infection and comorbidities, were adjusted for. Results 150 cases with RTD (proxy for Delta) and 1486 cases without RTD (proxy for Omicron) were included. Cases without RTD had a lower hazard of admission (adjusted Hazard Ratio [aHR] of 0.56, 95% confidence interval [CI] 0.34-0.91). Complete vaccination was protective of admission with an aHR of 0.45 (95%CI 0.26-0.77). Conclusion Omicron has resulted in a lower risk of hospital admission, compared to contemporaneous Delta infection in the Western Cape Province, when using the proxy marker of RTD. Under-ascertainment of reinfections with an immune escape variant like Omicron remains a challenge to accurately assessing variant virulence.

Abstract Background and aims Food addiction (FA) and substance use (SU) have frequently been reported in patients with eating disorders (EDs). Our study aimed to assess the prevalence rates of FA and/or lifetime problematic alcohol and illicit drug use among patients with specific ED, such as: bulimia nervosa (BN), binge eating disorder (BED), and other specified feeding and eating disorder (OSFED). We sought to identify clinical, psychopathological, and personality profiles involved in these addictive behavior-based phenotypes. Methods The total sample was 527 patients (176 BN, 115 BED, and 236 OSFED). FA was assessed through the Yale Food Addiction Scale 2.0. To determine lifetime SU, a semi-structured clinical interview was carried out. Results Patients with BN had the highest rates of FA both with and without SU. No gender differences were obtained for the prevalence of current FA and/or lifetime SU. Patients reporting at least one addictive-related behavior exhibited increased clinical severity compared to those who reported none. Increased impulsivity (such as high lack of premeditation, sensation seeking, and positive urgency) and low self-directedness were differentiating factors for presenting one or two addictive behaviors. Discussion and Conclusions Overall, patients presenting with at least one addictive-like behavior reported a poorer clinical status than those without. Also, patients with FA and SU exhibited a more dysfunctional profile characterized by high impulsivity and low self-directedness. These findings would support the need for targeted treatments to reduce impulsivity and increase self-directedness, especially in patients with any addictive-related behavior, as a step towards improving their treatment outcome.

2022 ◽  
Vol 6 (1) ◽  
Niaz Albarzinji ◽  
Sherzad Ali Ismael ◽  
Dashty Albustany

Abstract Background Rheumatoid arthritis is a complex multifactorial chronic disease, the importance of human leukocytic antigen (HLA) as a major genetic risk factor for rheumatoid arthritis was studied worldwide. The objective of this study is to identify the association of HLA-DRB1 subtypes with rheumatoid arthritis and its severity in Kurdish region. Methods A case–control study recruited 65 rheumatoid arthritis patients and 100 healthy individuals as control group all over the Kurdistan region/Iraq. Both patient and control groups are genotyped using polymerase chain reaction with sequence specific primer. Anti-CCP antibodies were measured by ELISA test. Rheumatoid factor, C-reactive protein, and disease activity score 28 which measured by DAS-28 values were calculated. The DAS-28 was used to assess the clinical severity of the patients. Results HLA-DRB1-0404 and HLA-DRB1-0405 frequencies showed a strong association with disease susceptibility (P < 0.001). The frequency of HLA-DRB1-0411 and HLA-DRB1-0413 were significantly higher in control group (P < 0.001). The frequency of rheumatoid factor and Anti-CCP were significantly higher among shared epitope-positive patients compared to shared epitope-negative patients (P < 0.001). Regarding the disease activity by DAS-28, rheumatoid arthritis patients didn’t show significant difference between the shared epitope-positive and shared epitope-negative patients. Conclusions HLA-DR0404 and HLA-DR0405 alleles are related to RA, while HLA-DR1-0411 and HLA-DRB1-0413 protect against RA in the Kurdistan region in the North of Iraq.

2022 ◽  
Piyush Kumar

BackgroundAcute treatment in emergency case management is required for survival and stabilization of critical patients, followed by a shifting to the relevant medical department for further care. However, for the seriously ill critical patients, i.e., when the care provided by the Emergency Department (ED) of the hospital is not enough to enable transfer, death may occur while treatment in the emergency department. This aspect of emergency management is often overlooked, and very few researcher and government is really serious regarding who dies in the ED. Aim and ObjectiveThe aim of my study was to determine the total Mortality occurring in India from 1st January 2019 to 31st May 2021(limitation here due to data availability is limited from accredited source) of emergency department admissions of public and private health facilities. The objective is to find out if there is increase or decrease in mortality of emergency department admissions during the covid-19 pandemic era by comparing average mortality of ED per month of public, private, rural, urban health facilities before the pandemic from 1st and 2nd year of pandemic i.e. 2020 and 2021 respectively MethodsThis research study is a cross sectional retrospective analysis of the mortality occurring at the emergency department of public and private, rural, urban hospitals from 1st January 2019 to May31st 2021 with aim to find out impact of covid-19. Electronic patient records from HMIS (health management information system) of MoHFW (ministry of health and family welfare) , Government of India is collected, observed, analyzed, compared for all patients deaths occurring at Emergency Department (ED) of public and private, rural, urban health facilities (n = 452102) during the period January 2019 to May 2021. ResultsThe study results found that largest total number of death occurred in the ED during may 2021 whereas the least number of deaths occurred in February 2019 (limitation is data availability up to May 2021 from accredited sources). During the first year of the pandemic, average mortality per month (Jan2020-Dec2020) in the emergency department (ED) of rural, urban, public and private hospitals in India was 16067per month whereas before the pandemic it was 12542 per month while during second year of pandemic i.e. 2021 the average mortality increased to 21758 per month (up to May 2021).DiscussionRecently a new strain omicron has again disrupted the normal life and lockdown and other measures are being implemented by different countries to save lives. The mortality at ED are having various etiologies, clinical severity at time of admission has a direct correlation with mortality, which requires the necessity of advanced triage system. There exists a lack of proper knowledge and advanced directives in the beginning i.e. December 2019 of the covid-19 pandemic era.Conclusions Due to novel disease majority of clinicians have challenging situation as well as Emergency Medicine (EM) teams faced a sudden increase in the number of cases with limited resources. Furthermore, a lack of proper knowledge and directives may have hindered access to proper care, as witnessed in many part of the world and available in various literatures. The authors hope that this study will help global researchers as well as policy makers to promote further research and discussion into preparation methods for such pandemics to reduce patient’s risk of death in the ED. KeywordsEmergency department, Death, Covid-19, Pandemic, Health facilities,

2022 ◽  
Vol 12 ◽  
Simone Negrini ◽  
Paola Contini ◽  
Giuseppe Murdaca ◽  
Francesco Puppo

Allergy is an inflammatory process determined by a cascade of immune events characterized by T-helper 2 lymphocytes polarization leading to interleukin-4 upregulation, IgE secretion, and mast cell and eosinophil activation. HLA-G molecules, both in membrane-bound and in soluble forms, are known to play a key immunoregulatory role and their involvement in allergic diseases is supported by increasing literature data. HLA-G expression and secretion is specifically induced in peripheral blood mononuclear cells of allergic patients after in vitro incubation with the causal allergen. Elevated levels of soluble HLA-G molecules are detected in serum of patients with allergic rhinitis correlating with allergen-specific IgE levels, clinical severity, drug consumption and response to allergen-specific immunotherapy. HLA-G genetic polymorphisms confer susceptibility to allergic asthma development and high levels of soluble HLA-G molecules are found in plasma and bronchoalveolar lavage fluid of patients with allergic asthma correlating with allergen-specific IgE levels. Interestingly, allergic pregnant women have lower plasma sHLA-G levels than non-allergic women during the 3rd trimester of pregnancy and at delivery. Finally, in allergic patients with atopic dermatitis HLA-G molecules are expressed by T cells, monocytes-macrophages and Langerhans cells infiltrating the dermis. Although at present is difficult to completely define the role of HLA-G molecules in allergic diseases, it may be suggested that they are specifically expressed and secreted by immune cells during the allergic reaction in an attempt to suppress allergic inflammation.

Neurology ◽  
2022 ◽  
pp. 10.1212/WNL.0000000000013225
Szu-Ju Chen ◽  
Chieh-Chang Chen ◽  
Hsin-Yu Liao ◽  
Ya-Ting Lin ◽  
Yu-Wei Wu ◽  

Background and Objectives:Short-chain fatty acids (SCFAs) are gut microbial metabolites that promote the disease process in a rodent model of Parkinson’s disease (PD), but fecal levels of SCFAs in PD patients are reduced. Simultaneous assessments of fecal and plasma SCFA levels, and their inter-relationships with the PD disease process are scarce. We aimed to compare fecal and plasma levels of different SCFAs subtypes in PD patients and healthy controls to delineate their interrelations and link to gut microbiota changes and clinical severity of PD.Methods:A cohort of 96 PD patients and 85 controls were recruited from National Taiwan University Hospital. Fecal and plasma concentrations of SCFAs were measured using chromatography and mass spectrometry. Gut microbiota was analyzed using metagenomic shotgun sequencing. Body mass index and medical co-morbidities were evaluated, and dietary information was obtained using a food frequency questionnaire. To assess motor and cognitive impairment, we used the Movement Disorder Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) and the Mini-Mental Status Examination (MMSE).Results:Compared with controls, PD patients had lower fecal but higher plasma concentrations of acetate, propionate, and butyrate. After adjustment for age, sex, disease duration, and anti-PD medication dosage, MDS-UPDRS part III motor scores correlated with reduced fecal levels of acetate (ρ = -0.37, p = 0.012), propionate (ρ = -0.32, p = 0.036), and butyrate (ρ = -0.40, p = 0.004) and with increased plasma propionate concentrations (ρ = 0.26, p = 0.042) in PD patients. MMSE scores negatively correlated with plasma levels of butyrate (ρ = -0.09, p = 0.027) and valerate (ρ = -0.032, p = 0.033) after adjustment for confounders. SCFAs-producing gut bacteria correlated positively with fecal levels of SCFAs in healthy controls but revealed no association in patients with PD. In the PD patient group, the abundance of pro-inflammatory microbes, such as Clostridiales bacterium NK3B98 and Ruminococcus sp. AM07-15, significantly correlated with decreased fecal levels and increased plasma levels of SCFAs, especially propionic acid.Discussion:Reductions in fecal SCFAs but increased plasma SCFAs were observed in PD patients and corelated to specific gut microbiota changes and the clinical severity of PD.Classification of evidence:This study provides Class III evidence that gut metabolite SCFAs distinguish between PD patients and controls, and are associated with disease severity in patients with PD.

Toxins ◽  
2022 ◽  
Vol 14 (1) ◽  
pp. 44
Harald Hefter ◽  
Beyza Ürer ◽  
Raphaela Brauns ◽  
Dietmar Rosenthal ◽  
Sven G. Meuth ◽  

Under continuous long-term treatment with abo- or onabotulinum toxin type A (BoNT/A), ~10 to 15% of patients with cervical dystonia (CD) will develop neutralizing antibodies and reduced responsiveness over an ~10-year treatment period. Among the botulinum neurotoxin type A preparations so far licensed for CD, incobotulinum toxin A (incoBoNT/A; Xeomin®) is the only one without complex proteins. Whether CD patients with treatment failure under abo- or onaBoNT/A may still respond to incoBoNT/A is unknown. In this cross-sectional, retrospective study, 64 CD patients with secondary treatment failure after abo- or onaBoNT/A therapy who were switched to incoBoNT/A were compared to 34 CD patients exclusively treated with incoBoNT/A. The initial clinical severity of CD, best outcome during abo- or onaBoNT/A therapy, severity at the time of switching to incoBoNT/A and severity at recruitment, as well as all corresponding doses, were analyzed. Furthermore, the impact of neutralizing antibodies (NABs) on the long-term outcome of incoBoNT/A therapy was evaluated. Patients significantly improved after the switch to incoBoNT/A (p < 0.001) but did not reach the improvement level obtained before the development of partial secondary treatment failure or that of patients who were exclusively treated with incoBoNT/A. No difference between abo- and onaBoNT/A pretreatments or between the long-term outcomes of NAB-positive and NAB-negative patients was found. The present study demonstrates significant long-term improvement after a switch to incoBoNT/A in patients with preceding secondary treatment failure after abo- or onaBoNT/A therapy and confirms the low antigenicity of incoBoNT/A.

PLoS ONE ◽  
2022 ◽  
Vol 17 (1) ◽  
pp. e0262356
Jorge Luis Vélez-Páez ◽  
Pedro Legua ◽  
Pablo Vélez-Páez ◽  
Estefanía Irigoyen ◽  
Henry Andrade ◽  

Introduction Sepsis is a public health problem due to its high prevalence and mortality. Mean platelet volume (MPV), a biomarker reported in routine blood counts, has been investigated and shows promise for determining fatal outcomes in septic patients. Objective Evaluate whether the mean platelet volume (MPV) and mean platelet volume-to-platelet count (MPV/P) ratio are predictors of clinical severity and mortality in patients with sepsis. Methods A prospective population cohort of 163 patients aged 18–97 years was recruited at the Intensive Care Unit of Pablo Arturo Hospital, Quito, Ecuador from 2017–2019 and followed up for 28 days. Patients were diagnosed with sepsis based on SEPSIS-3 septic shock criteria; in which the MPV and the MPV/P ratio were measured on days 1, 2, and 3. Sequential organ failure assessment (SOFA) score and presence of septic shock assessed clinical severity. Mortality on day 28 was considered the fatal outcome. Results The average age of the patients was 61,15 years (SD 20,94) and female sex was predominant. MPV cutoff points at days 1, 2 and 3 were >9,45fL, >8,95fL and >8, 85fL; and (MPV/P) ratio >8, 18, >4, 12 y >3, 95, respectively. MPV at days 2 (9,85fL) and 3 (8,55fL) and (MPV/P) ratio at days 1 (4,42), 2 (4,21), and 3 (8,55), were predictors of clinical severity assessed by septic shock, which reached significance in the ROC curves. MPV and (MPV/P) ratio were also predictors of clinical severity determined by SOFA at days 1, 2, and 3, where higher values were observed in non-survivors reaching significance in all categories. MPV and MPV/P ratio at days 1, 2 and 3 were independent predictor factors of mortality using Cox proportional hazards model (HR 2,31; 95% CI 1,36–3,94), (HR 2,11; 95% CI 1,17–3,82), (HR 2,13; 95% CI 1,07–4,21) and (HR 2,38; 95% CI 1,38–4,12), (HR 2,15; 95% CI 1,14–4,06), (HR 4,43; 95% CI, 1,72–11,37) respectively. Conclusions MPV and the MPV/P ratio are predictors of clinical severity and mortality in sepsis. The MPV and its coefficient are indicators of the biological behavior of platelets in sepsis. They should be considered as a cost-effective and rapidly available tool that guides the treatment.

2022 ◽  
Vol 16 (1) ◽  
pp. e0010048
Li Li ◽  
Zhi-Gang Han ◽  
Peng-Zhe Qin ◽  
Wen-Hui Liu ◽  
Zhou Yang ◽  

Background The first community transmission of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Delta variant of concern (VOC) in Guangzhou, China occurred between May and June 2021. Herein, we describe the epidemiological characteristics of this outbreak and evaluate the implemented containment measures against this outbreak. Methodology/Principal findings Guangzhou Center for Disease Control and Prevention provided the data on SARS-CoV-2 infections reported between 21 May and 24 June 2021. We estimated the incubation period distribution by fitting a gamma distribution to the data, while the serial interval distribution was estimated by fitting a normal distribution. The instantaneous effective reproductive number (Rt) was estimated to reflect the transmissibility of SARS-CoV-2. Clinical severity was compared for cases with different vaccination statuses using an ordinal regression model after controlling for age. Of the reported local cases, 7/153 (4.6%) were asymptomatic. The median incubation period was 6.02 (95% confidence interval [CI]: 5.42–6.71) days and the means of serial intervals decreased from 5.19 (95% CI: 4.29–6.11) to 3.78 (95% CI: 2.74–4.81) days. The incubation period increased with age (P<0.001). A hierarchical prevention and control strategy against COVID-19 was implemented in Guangzhou, with Rt decreasing from 6.83 (95% credible interval [CrI]: 3.98–10.44) for the 7-day time window ending on 27 May 2021 to below 1 for the time window ending on 8 June and thereafter. Individuals with partial or full vaccination schedules with BBIBP-CorV or CoronaVac accounted for 15.3% of the COVID-19 cases. Clinical symptoms were milder in partially or fully vaccinated cases than in unvaccinated cases (odds ratio [OR] = 0.26 [95% CI: 0.07–0.94]). Conclusions/Significance The hierarchical prevention and control strategy against COVID-19 in Guangzhou was timely and effective. Authorised inactivated vaccines are likely to contribute to reducing the probability of developing severe disease. Our findings have important implications for the containment of COVID-19.

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