Variation In Disease Severity Research Articles

Racial variability in immune responses only partially explains differential systemic sclerosis disease severity

ObjectiveTo understand if autoantibodies account for racial variation in disease severity, we compared autoantibody distribution and associated phenotype between self-identified black and white systemic sclerosis (SSc) patients.Methods803 black and 2178...

Anxiety Symptoms and Disease Severity in Parkinson Disease.

BACKGROUND: Anxiety is prevalent in Parkinson disease (PD), negatively affecting quality of life for patients and their families. Targeted anxiety interventions are needed that account for variables such as disease severity; however, there is insufficient evidence regarding the trajectory of anxiety along the disease course. OBJECTIVE: The aim of this study was to investigate the association between disease severity and anxiety symptoms in a PD sample. METHODS: This descriptive study used secondary data analyses of data from a web-based survey study of individuals with PD in the United States. Participants were 21 years or older, had access to the Internet, and were given a diagnosis of PD (N = 72). We performed multiple regression analyses to assess the relationship between patient-reported disease severity and anxiety symptoms. RESULTS: There was a statistically significant association between disease severity and anxiety symptoms in people with PD, after controlling for all 5 explanatory variables (sex, age, wearing off, disease severity, and disease duration) (P < .001). Age and wearing off PD medication also had statistically significant, although smaller, effects on anxiety symptoms (P < .05). CONCLUSION: Disease severity was related to increased anxiety symptoms among individuals with PD. Anxiety intervention research is needed, and future studies should account for variations in disease severity and medication effects in both intervention and study design.

LungViT: Ensembling Cascade of Texture Sensitive Hierarchical Vision Transformers for Cross-Volume Chest CT Image-to-Image Translation.

Chest computed tomography (CT) at inspiration is often complemented by an expiratory CT to identify peripheral airways disease. Additionally, co-registered inspiratory-expiratory volumes can be used to derive various markers of lung function. Expiratory CT scans, however, may not be acquired due to dose or scan time considerations or may be inadequate due to motion or insufficient exhale; leading to a missed opportunity to evaluate underlying small airways disease. Here, we propose LungViT- a generative adversarial learning approach using hierarchical vision transformers for translating inspiratory CT intensities to corresponding expiratory CT intensities. LungViT addresses several limitations of the traditional generative models including slicewise discontinuities, limited size of generated volumes, and their inability to model texture transfer at volumetric level. We propose a shifted-window hierarchical vision transformer architecture with squeeze-and-excitation decoder blocks for modeling dependencies between features. We also propose a multiview texture similarity distance metric for texture and style transfer in 3D. To incorporate global information into the training process and refine the output of our model, we use ensemble cascading. LungViT is able to generate large 3D volumes of size 320×320×320 . We train and validate our model using a diverse cohort of 1500 subjects with varying disease severity. To assess model generalizability beyond the development set biases, we evaluate our model on an out-of-distribution external validation set of 200 subjects. Clinical validation on internal and external testing sets shows that synthetic volumes could be reliably adopted for deriving clinical endpoints of chronic obstructive pulmonary disease.

Clinical Profile and Course of Patients with Acute Respiratory Distress Syndrome due to COVID-19 in a Middle-Income Region in Mexico.

COVID-19 leads to severe clinical complications that culminate in respiratory failure and acute respiratory distress syndrome (ARDS). Despite reports of some comorbidities that contribute to the development of COVID-19-mediated ARDS, there is great variation in mortality rates among critical COVID-19 patients in the world. To date, no studies have described the incidence and comorbidities associated with ARDS due to COVID-19 in the northeastern region of Mexico. To describe patients diagnosed with ARDS due to COVID-19 in the northeastern region of Mexico, as well as its variations in comparison with other regions of the country. We conducted a prospective and observational study in a tertiary care center in Northeastern Mexico. All patients diagnosed with SARS-CoV-2 infection and requiring management in the intensive care unit were included. We developed a database that was updated daily with the patients' demographic information, pre-existing diseases, disease severity, and clinical variables. The incidence of ARDS secondary to COVID-19 in HRAEV was high in comparison with other reports. Diabetes mellitus was the risk factor most associated with COVID-19-mediated ARDS. Based on our findings and those previously reported in the literature, there are differences that we discuss between northeastern and central Mexico, and analyze other areas evaluated around the world.

Treatment options for patients with pilonidal sinus disease: PITSTOP, a mixed-methods evaluation.

There is no consensus on optimal management of pilonidal disease. Surgical practice is varied, and existing literature is mainly single-centre cohort studies of varied disease severity, interventions and outcome assessments. A prospective cohort study to determine: • disease severity and intervention relationship • most valued outcomes and treatment preference by patients • recommendations for policy and future research. Observational cohort study with nested mixed-methods case study. Discrete choice experiment. Clinician survey. Three-stage Delphi survey for patients and clinicians. Inter-rater reliability of classification system. Thirty-one National Health Service trusts. Patients aged > 16 years referred for elective surgical treatment of pilonidal disease. Surgery. Pain postoperative days 1 and 7, time to healing and return to normal activities, complications, recurrence. Outcomes compared between major and minor procedures using regression modelling, propensity score-based approaches and augmented inverse probability weighting to account for measured potential confounding features. Clinician survey: There was significant heterogeneity in surgeon practice preference. Limited training opportunities may impede efforts to improve practice. Cohort study: Over half of patients (60%; N = 667) had a major procedure. For these procedures, pain was greater on day 1 and day 7 (mean difference day 1 pain 1.58 points, 95% confidence interval 1.14 to 2.01 points, n = 536; mean difference day 7 pain 1.53 points, 95% confidence interval 1.12 to 1.95 points, n = 512). There were higher complication rates (adjusted risk difference 17.5%, 95% confidence interval 9.1 to 25.9%, n = 579), lower recurrence (adjusted risk difference -10.1%, 95% confidence interval -18.1 to -2.1%, n = 575), and longer time to healing (>34 days estimated difference) and time to return to normal activities (difference 25.9 days, 95% confidence interval 18.4 to 33.4 days). Mixed-methods analysis: Patient decision-making was influenced by prior experience of disease and anticipated recovery time. The burden involved in wound care and the gap between expected and actual time for recovery were the principal reasons given for decision regret. Discrete choice experiment: The strongest predictors of patient treatment choice were risk of infection/persistence (attribute importance 70%), and shorter recovery time (attribute importance 30%). Patients were willing to trade off these attributes. Those aged over 30 years had a higher risk tolerance (22.35-34.67%) for treatment failure if they could experience rapid recovery. There was no strong evidence that younger patients were willing to accept higher risk of treatment failure in exchange for a faster recovery. Patients were uniform in rejecting excision-and-leave-open because of the protracted nursing care it entailed. Wysocki classification analysis: There was acceptable inter-rater agreement (κ = 0.52, 95% confidence interval 0.42 to 0.61). Consensus exercise: Five research and practice priorities were identified. The top research priority was that a comparative trial should broadly group interventions. The top practice priority was that any interventions should be less disruptive than the disease itself. Incomplete recruitment and follow-up data were an issue, particularly given the multiple interventions. Assumptions were made regarding risk adjustment. Results suggest the burden of pilonidal surgery is greater than reported previously. This can be mitigated with better selection of intervention according to disease type and patient desired goals. Results indicate a framework for future higher-quality trials that stratify disease and utilise broad groupings of common interventions with development of a patient-centred core outcome set. This trial is registered as ISRCTN95551898. This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 17/17/02) and is published in full in Health Technology Assessment; Vol. 28, No. 33. See the NIHR Funding and Awards website for further award information.

Marine actinomycetes for biocontrol of Fusarium solani in tomato plants: In vitro and in vivo studies

Using microorganisms as biocontrol agents of phytopathogens has been an alternative to synthetic fungicides. Actinomycetes isolated from soil and plants have reduced diseases caused by phytopathogens; however, microorganisms from marine environments may be an option as biocontrol agents. The tomato crop possesses an important economic impact worldwide, being Mexico the main exporter. Several species of Fusarium cause damage to tomato crops and are controlled with synthetic fungicides. The objective of this work was to determine the effect of marine actinomycetes as biocontrol on Fusarium solani in tomato plants. Four strains of marine actinomycetes (A20, A19, A18, and A15) and one terrestrial actinomycete (ED48) were used. The actinomycetes strains used, produced siderophores. The greatest inhibition of mycelial growth of F. solani due to iron competition was obtained by strain A19 with 74.28%. Only two actinomycetes showed antifungal activity by VOCs (A19 and A18), strain A19 showed the highest antagonistic activity with PICR of 76.75%. Actinomycetes treatments showed significant differences with synthetic fungicide application in growth, disease severity (SE), and disease incidence (DI) variables. The application of marine actinomycete (A19) on plants infested with F. solani increased the levels of enzyme activity (SOD, POD, CAT, and PAL) versus plants in that only F. solani and distilled water (control) were applied. Actinomycetes of marine origin are an option as biocontrol agents for F. solani.

Exploratory multi-omics analysis reveals host-microbe interactions associated with disease severity in psoriatic skin

Psoriasis (Pso) is a chronic inflammatory skin disease that poses both physical and psychological challenges. Dysbiosis of the skin microbiome has been implicated in Pso, yet a comprehensive multi-omics analysis of host-microbe interactions is still lacking. To bridge this gap, we conducted an exploratory study by adopting the integrated approach that combines whole metagenomic shotgun sequencing with skin transcriptomics. This was a cross-sectional study, adult patients with plaque-type Psoriasis (Pso) and healthy volunteers were included. Skin microbiota samples and biopsies were collected from both lesional and non-lesional skin areas on the lower back. Weighted Gene Correlation Network Analysis (WGCNA) was employed for co-expression network analysis, and cell deconvolution was conducted to estimate cell fractions. Taxonomic and functional features of the microbiome were identified using whole metagenomic shotgun sequencing. Association between host genes and microbes was analyzed using Spearman correlation. Host anti-viral responses and interferon-related networks were identified and correlated with the severity of psoriasis. The skin microbiome showed a greater prevalence of Corynebacterium simulans in the PASI severe-moderate groups, which correlated with interferon-induced host genes. Two distinct psoriatic clusters with varying disease severities were identified. Variations in the expression of cell apoptosis-associated antimicrobial peptides (AMPs) and microbial aerobic respiration I pathway may partly account for these differences in disease severity. Our multi-omics analysis revealed for the first time anti-viral responses and the presence of C.simulans associated with psoriasis severity. It also identified two psoriatic subtypes with distinct AMP and metabolic pathway expression. Our study provides new insights into understanding the host-microbe interaction in psoriasis and lays the groundwork for developing subtype-specific strategies for managing this chronic skin disease. The research has received funding from the FP7 (MAARS-Grant 261366) and the Innovative Medicines Initiative 2 Joint Undertaking (JU) under grant agreement No 821511 (BIOMAP). The JU receives support from the European Union's Horizon 2020 research and innovation programme and EFPIA. This publication reflects only the author's view and the JU is not responsible for any use that may be made of the information it contains. GAM was supported by a scholarship provided by CAPES-PRINT, financed by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES (Brazilian Government Agency). The authors thank all patients who participated in our study.

Short Cilia, Immunodeficiency, and Cystic Fibrosis in a Mother-Daughter Pair

Patients with chronic rhinosinusitis (CRS) that is refractory to maximal medical and surgical therapy should be evaluated for other primary conditions. Cystic fibrosis (CF), primary immunodeficiency (PID), and primary ciliary dyskinesia (PCD) are potential risk factors for refractory CRS. These conditions present with variable disease severity and diagnosis may be delayed into adulthood. We report a case of a mother-daughter pair with CRS refractory to maximal medical management. The patients were further evaluated and found to have features consistent with CF, PID, and PCD. All 3 are rare disorders and thought to cause CRS in isolation. Patients with refractory CRS should be further evaluated to identify alternative diagnoses and ensure proper management. Refractory CRS may be multifactorial, with different risk factors simultaneously contributing to its persistence.

Obstructive Sleep Apnea and Oxygenation in Very Old Adults: A Propensity-Score Match Study

ObjectivesThe prevalence of obstructive sleep apnea (OSA) escalates with advancing age. Although the apnea-hypopnea index (AHI) is the standard measure for assessing OSA severity, it does not account for additional oximetric parameters that may influence disease progression in older adults. This study aimed to evaluate disparities in respiratory polygraphy/polysomnography parameters among patients with OSA, stratified by age and sex. DesignRetrospective propensity score-matched study. Setting and ParticipantsSleep unit of a university hospital; 11,747 participants, 210 aged 80 years or older. MethodsPropensity score matching was used to establish 4 age cohorts, with the 210 oldest adults serving as the reference group. Primary outcome variables included the total sleep time with oxygen saturation (SaO2) below 90% (T90), average SaO2, minimum SaO2, and AHI. The association between T90 and AHI, as well as the severity of OSA, was assessed across the 4 age categories. ResultsDespite comparable AHI scores, the oldest patients with OSA exhibited the highest T90 and the lowest SaO2 levels compared to younger counterparts. The proportion of patients with severe OSA and T90 in the highest quartile increased with age: 12.5% in young adults, 14.8% in adults, 21.7% in the old, and 34% in the very old participants (P < .001). old and very old patients had a greater likelihood of being in the most severe OSA category compared to the younger ones, with odds ratios (OR) 2.57 (95% CI 1.42–4.65) and 5.52 (95% CI 3.06–9.97), respectively. These patterns were more pronounced in women of advanced age, indicating a sex-specific variation in disease severity with increasing age. Conclusions and ImplicationsOld patients with OSA, particularly women, demonstrate elevated T90 and reduced SaO2 levels, irrespective of AHI, indicating a hypoxemia increased risk. The diagnostic criteria, management, and outcomes for OSA may require adaptations to address the unique needs of very old populations.

Virulence Comparison of a Comprehensive Panel of Xylella fastidiosa Pierce's Disease Isolates from California.

Xylella fastidiosa, the causal agent of Pierce's disease of grapevine, has been found in all major grape-growing regions in California, U.S.A. Large collections of X. fastidiosa isolates are available from these areas, which enable comparative studies of pathogen genetic traits and virulence. Owing to the significant resource requirements for experiments with X. fastidiosa in grapevine, however, most studies use only a single isolate to evaluate disease, and it is not clear how much variability between isolates impacts disease development in experimental or natural settings. In this study, a comprehensive panel of X. fastidiosa isolates from all California grape-growing regions was tested for virulence in susceptible grapevine and in the model host plant, tobacco. Seventy-one isolates were tested, 29 in both grapevine and tobacco. The results of this study highlight the inherent variability of inoculation experiments with X. fastidiosa, including variation in disease severity in plants inoculated with a single isolate, and variability between experimental replicates. There were limited differences in virulence between isolates that were consistent across experimental replicates, or across different host plants. This suggests that choice of isolate within the X. fastidiosa subsp. fastidiosa Pierce's disease group may not make any practical difference when testing in susceptible grape varieties, and that pathogen evolution has not significantly changed virulence of Pierce's disease isolates within California. The location of isolation also did not dictate relative disease severity. This information will inform experimental design for future studies of X. fastidiosa in grapevine and provide important context for genomic research.

Pathogenic variations in Colletotrichum spp. causing chilli anthracnose in Peninsular Malaysia

AbstractIn Peninsular Malaysia, Colletotrichum fioriniae, Colletotrichum fructicola, Colletotrichum scovillei, Colletotrichum siamense and Colletotrichum truncatum are the causative pathogens of chilli anthracnose. In the present study, the pathogenic variability and virulence levels of these five Colletotrichum spp. were evaluated. Isolates of C. fioriniae, C. fructicola, C. scovillei, C. siamense and C. truncatum were tested for pathogenicity using red and green Capsicum annuum and red and green Capsicum frutescens. Pathogenicity tests were conducted using spore suspensions and mycelial plugs on wounded and nonwounded chilli fruits. All isolates tested on the wounded chilli fruits caused anthracnose symptoms with variable disease severity and virulence. In nonwounded chilli fruits, only isolates of C. scovillei (n = 7) and C. truncatum (n = 5) caused infection. C. fioriniae, C. fructicola, C. scovillei, C. siamense and C. truncatum showed variability in pathogenicity and virulence levels in red and green chilli fruits of Ca. annuum and Ca. frutescens. Pathogenicity tests on wounded and nonwounded chilli fruits can be used to identify pathotypes within anthracnose pathogen populations. This is important for strategizing the effective disease management of chilli anthracnose.

Survival and causes of death in patients with alpha and beta-thalassemia in Northern Thailand

Background Thalassemia is the most prevalent hereditary anaemia worldwide. Severe forms of thalassemia can lead to reduced life expectancy due to disease-related complications. Objectives To investigate the survival of thalassemia patients across varying disease severity, causes of death and related clinical factors. Patients and methods We conducted a retrospective review of thalassemia patients who received medical care at Chiang Mai University Hospital. The analysis focused on survival outcomes, and potential associations between clinical factors and patient survival. Results A total of 789 patients were included in our study cohort. Among them, 38.1% had Hb H disease, 35.4% had Hb E/beta-thalassemia and 26.5% had beta-thalassemia major. Half of the patients (50.1%) required regular transfusions. Sixty-five patients (8.2%) had deceased. The predominant causes of mortality were infection-related (36.9%) and cardiac complications (27.7%). Transfusion-dependent thalassemia (TDT) (adjusted HR 3.68, 95% CI 1.39–9.72, p = 0.008) and a mean serum ferritin level ≥3000 ng/mL (adjusted HR 4.18, 95% CI 2.20–7.92, p < 0.001) were independently associated with poorer survival. Conclusions Our study highlights the primary contributors to mortality in patients with thalassemia as infection-related issues and cardiac complications. It also underscores the significant impact of TDT and elevated serum ferritin levels on the survival of thalassemia patients.

Wiskott-Aldrich syndrome: a study of 577 patients defines the genotype as a biomarker for disease severity and survival

AbstractWiskott-Aldrich syndrome (WAS) is a multifaceted monogenic disorder with a broad disease spectrum and variable disease severity and a variety of treatment options including allogeneic hematopoietic stem cell transplantation (HSCT) and gene therapy (GT). No reliable biomarker exists to predict disease course and outcome for individual patients. A total of 577 patients with a WAS variant from 26 countries and a median follow-up of 8.9 years (range, 0.3-71.1), totaling 6118 patient-years, were included in this international retrospective study. Overall survival (OS) of the cohort (censored at HSCT or GT) was 82% (95% confidence interval, 78-87) at age 15 years and 70% (61-80) at 30 years. The type of variant was predictive of outcome: patients with a missense variant in exons 1 or 2 or with the intronic hot spot variant c.559+5G>A (class I variants) had a 15-year OS of 93% (89-98) and a 30-year OS of 91% (86-97), compared with 71% (62-81) and 48% (34-68) in patients with any other variant (class II; P < .0001). The cumulative incidence rates of disease-related complications such as severe bleeding (P = .007), life-threatening infection (P < .0001), and autoimmunity (P = .004) occurred significantly later in patients with a class I variant. The cumulative incidence of malignancy (P = .6) was not different between classes I and II. It confirms the spectrum of disease severity and quantifies the risk for specific disease-related complications. The class of the variant is a biomarker to predict the outcome for patients with WAS.

Randomized Trial of a Selective Aldose Reductase Inhibitor in Patients With Diabetic Cardiomyopathy

BackgroundProgression to symptomatic heart failure is a complication of type 2 diabetes; heart failure onset in this setting is commonly preceded by deterioration in exercise capacity. ObjectivesThis study sought to determine whether AT-001, a highly selective aldose reductase inhibitor, can stabilize exercise capacity among individuals with diabetic cardiomyopathy (DbCM) and reduced peak oxygen uptake (Vo2). MethodsA total of 691 individuals with DbCM meeting inclusion and exclusion criteria were randomized to receive placebo or ascending doses of AT-001 twice daily. Stratification at inclusion included region of enrollment, cardiopulmonary exercise test results, and use of sodium-glucose cotransporter 2 inhibitors or glucagon-like peptide-1 receptor agonists. The primary endpoint was proportional change in peak Vo2 from baseline to 15 months. Subgroup analyses included measures of disease severity and stratification variables. ResultsThe mean age was 67.5 ± 7.2 years, and 50.4% of participants were women. By 15 months, peak Vo2 fell in the placebo-treated patients by −0.31 mL/kg/min (P = 0.005 compared to baseline), whereas in those receiving high-dose AT-001, peak Vo2 fell by −0.01 mL/kg/min (P = 0.21); the difference in peak Vo2 between placebo and high-dose AT-001 was 0.30 (P = 0.19). In prespecified subgroup analyses among those not receiving sodium-glucose cotransporter 2 inhibitors or glucagon-like peptide-1 receptor agonists at baseline, the difference between peak Vo2 in placebo vs high-dose AT-001 at 15 months was 0.62 mL/kg/min (P = 0.04; interaction P = 0.10). ConclusionsAmong individuals with DbCM and impaired exercise capacity, treatment with AT-001 for 15 months did not result in significantly better exercise capacity compared with placebo. (Safety and Efficacy of AT-001 in Patients With Diabetic Cardiomyopathy [ARISE-HF]; NCT04083339)

The germ theory revisited: A noncentric view on infection outcome

The germ theory states that pathogenic microorganisms are responsible for causing infectious diseases. The theory is inherently microbe-centric and does not account for variability in disease severity among individuals and asymptomatic carriership—two phenomena indicating an important role for host variability in infection outcome. The basic tenet of the germ theory was recently challenged, and a radically host-centric paradigm referred to as the “full-blown host theory” was proposed. According to this view, the pathogen is reduced to a passive environmental trigger, and the development of disease is instead due to pre-existing immunodeficiencies of the host. Here, we consider the factors that determine disease severity using established knowledge concerning evolutionary biology, microbial pathogenesis, and host–pathogen interactions. We note that the available data support a noncentric view that recognizes key roles for both the causative microbe and the host in dictating infection outcome.

Updated mutational spectrum and genotype-phenotype correlations in ichthyosis patients with ABCA12 pathogenic variants.

Autosomal recessive congenital ichthyoses (ARCI) is a genetically heterogeneous condition that can be caused by pathogenic variants in at least 12 genes, including ABCA12. ARCI mainly consists of congenital ichthyosiform erythroderma (CIE), lamellar ichthyosis (LI) and harlequin ichthyosis (HI). The objective was to determine previously unreported pathogenic variants in ABCA12 and to update genotype-phenotype correlations for patients with pathogenic ABCA12 variants. Pathogenic variants in ABCA12 were detected using Sanger sequencing or a combination of Sanger sequencing and whole-exome sequencing. To verify the pathogenicity of a previously unreported large deletion and intron variant, cDNA analysis was performed using total RNA extracted from hair roots. Genetic analyses were performed on the patients with CIE, LI, HI and non-congenital ichthyosis with unusual phenotypes (NIUP), and 11 previously unreported ABCA12 variants were identified. Sequencing of cDNA confirmed the aberrant splicing of the variant ABCA12 in the patients with the previously unreported large deletion and intron variant. Our findings expand the phenotype spectrum of ichthyosis patients with ABCA12 pathogenic variants. The present missense variants in ABCA12 are considered to be heterogenous in pathogenicity, and they lead to varying disease severities in patients with ARCI and non-congenital ichthyosis with unusual phenotypes (NIUP).

Objectively assessed sleep quality parameters in Multiple Sclerosis at home: Association to disease, disease severity and physical activity

BackgroundMultiple Sclerosis (MS) is a chronic inflammatory autoimmune, neurodegenerative disease that affects regular mobility and leads predominantly to physical disability. Poor sleep quality, commonly reported in MS patients, impacts their physical activity (PA). Accelerometers monitor 24-h activity patterns, offering insights into disease progression in daily life. ObjectiveTo test if the sleep quality variables of MS patients, as assessed with wrist-worn accelerometers, differ from those of controls and are associated with PA and disease severity variables. MethodsSeven-day raw accelerometer data collected from 40 MS patients and 24 controls was processed using an open-source GGIR package, from which variables of sleep quality (sleep efficiency, wake after sleep onset (WASO), sleep regularity index (SRI), intradaily variability (IV)) and PA (of different intensities: inactivity, light (LPA), moderate (MPA), vigorous (VPA)) were analyzed. The variables were compared between the two study groups and in MS patients, correlation tested associations among the variables of sleep quality, PA, and disease severity (assessed with the Expanded Disability Status Scale, EDSS). ResultsSleep efficiency was the only variable that differed significantly between MS patients and controls (lower in MS, p = 0.01). Both SRI (positively) and IV (negatively) correlated with the time spent in LPA and MPA. WASO correlated negatively with inactivity. ConclusionThis is one of the few studies with a wrist-worn accelerometer that shows a difference in sleep efficiency between MS patients and controls and, in MS, an association of sleep quality variables with PA variables.

Hyposmia correlates with axial signs and gait disorder in Parkinson's disease: an Italian Olfactory Identification Test study.

Olfactory dysfunction is a non-motor symptom and an important biomarker of Parkinson's disease (PD) because of its high prevalence (> 90%). Whether hyposmia correlates with motor symptoms is unclear. In the present study, we aim to investigate the relationship between olfactory impairment with both motor and non-motor features and disease variables (disease duration, stage, and severity). One-hundred fifty-four PD patients were evaluated. Odor identification ability was tested using Italian Olfactory Identification Test (IOIT). A comprehensive spectrum of motor and non-motor features was assessed. Cognitive function was investigated through MMSE. Patients were divided into 3 different clinical phenotypes using UPDRS-III: tremor-dominant type (TDT), akinetic-rigid type (ART), and mixed type (MXT). Three of the 33 IOIT items were most frequently misidentified: basil (74.3%), coffee (66.9%), and mushroom (59.6%). Hyposmia was found in 93%. Hyposmic patients were older than controls (p = 0.01). Hoehn & Yahr (H&Y) score of 2 or greater was associated with higher probability of being hyposmic (OR = 5.2, p = 0.01). IOIT score did not significantly differ between TDT, ART, and MXT of analyzed PD patients. Performance to IOIT inversely correlated with age (p < 0.01), disease duration (p = 0.01), and H&Y score of 2 or higher (p < 0.01). Clinical features that associated with higher IOIT score were freezing of gait (FOG) (p < 0.001) and camptocormia (p < 0.05). In our cohort, IOIT scores showed a positive correlation with axial motor signs, but not with non-motor symptoms. IOIT may be a useful tool not only for supporting PD diagnosis but also for providing prognostic information about motor function.

The Association of Vitamin D Receptor Polymorphisms with COVID-19 Severity.

Association studies of vitamin D receptor (VDR) polymorphisms with COVID-19 severity have produced inconsistent results in different populations. Herein we examined VDR gene polymorphisms in a Caucasian Greek cohort of COVID-19 patients. This was a case-control study in a tertiary university hospital in Greece including 137 COVID-19 patients with varying disease severities and 72 healthy individuals. In total 209 individuals were genotyped for the FokI (rs10735810), ApaI (rs7975232), TaqI (rs731236) and BsmI (rs1544410) single-nucleotide polymorphisms (SNP) of the VDR gene by polymerase chain reaction and restriction fragment length polymorphism analysis (PCR-RFLPs). Statistical analyses were performed to determine the association between genotype and disease severity, adjusting for various confounding factors. Genotype distribution of the studied VDR SNPs in the control group was in Hardy-Weinberg equilibrium. The TaqI variant was differentially distributed between controls and COVID-19 patients according to the additive model (p = 0.009), and the CC genotype was significantly associated with an increased risk for severe COVID-19 according to the recessive model [OR: 2.52, 95%CI:1.2-5.29, p = 0.01]. Multivariate analysis demonstrated a robust association of COVID-19 severity and TaqI polymorphism in the recessive model even after adjusting for multiple confounders, including age, sex and CRP levels [Adj.OR:3.23, 95%CI:1.17-8.86, p = 0.023]. The distribution of FokI, ApaI and BsmI genotypes was similar between COVID-19 patients and controls. The CC genotype of TaqI polymorphism is significantly associated with an increased risk for severe COVID-19 independently of age, sex or degree of inflammation.

Iron dysregulation and inflammatory stress erythropoiesis associates with long-term outcome of COVID-19

Persistent symptoms following SARS-CoV-2 infection are increasingly reported, although the drivers of post-acute sequelae (PASC) of COVID-19 are unclear. Here we assessed 214 individuals infected with SARS-CoV-2, with varying disease severity, for one year from COVID-19 symptom onset to determine the early correlates of PASC. A multivariate signature detected beyond two weeks of disease, encompassing unresolving inflammation, anemia, low serum iron, altered iron-homeostasis gene expression and emerging stress erythropoiesis; differentiated those who reported PASC months later, irrespective of COVID-19 severity. A whole-blood heme-metabolism signature, enriched in hospitalized patients at month 1–3 post onset, coincided with pronounced iron-deficient reticulocytosis. Lymphopenia and low numbers of dendritic cells persisted in those with PASC, and single-cell analysis reported iron maldistribution, suggesting monocyte iron loading and increased iron demand in proliferating lymphocytes. Thus, defects in iron homeostasis, dysregulated erythropoiesis and immune dysfunction due to COVID-19 possibly contribute to inefficient oxygen transport, inflammatory disequilibrium and persisting symptomatology, and may be therapeutically tractable.