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Background Methods Key results Conclusions and Inferences Cyclic vomiting syndrome is a chronic disorder of gut‐brain interaction that is present in both adults and children. It is characterized by severe nausea, vomiting, abdominal pain, and several non‐GI symptoms. It is also associated with several comorbid conditions such as anxiety and depression, which affect overall health care outcomes.This article delineates treatment principles, encompassing both abortive interventions and prophylactic regimens currently recommended for CVS. However, it underscores a critical concern: the absence of FDA‐approved medications for CVS treatment, with existing therapies relying on retrospective and open‐labeled trials.This article emphasizes the pressing need for the development of CVS‐specific outcome assessment tools to facilitate more accurate evaluation and robust data collection for the future studies. In exploring this deficiency, the manuscript also presents the up‐to‐date data and development that enhances our comprehension of patient‐centric concepts, and the challenges faced in creating CVS‐specific tools, and presents a roadmap for their development. Addressing this gap is crucial for advancing our understanding of CVS and optimizing patient care.This elucidates the current state of CVS management but also advocates for a future where tailored tools enhance our ability to measure and improve the outcomes for individuals with this debilitating disorder. [ABSTRACT FROM AUTHOR]

Background and purpose Methods Results Conclusions Few data are available on the course of myasthenia gravis (MG) regarding disease severity and stability over time in real‐world settings. This study used the French National Health Insurance Database (SNDS) to assess markers of disease severity in patients with MG longitudinally.All patients with MG‐related claims in the SNDS between 2013 and 2020 were identified. Patients were followed for up to 8 years after the first claim. Intensive care unit (ICU) stays, treatment with intravenous immunoglobulin (IVIg) or plasma exchange (PE), and death were documented throughout the follow‐up period. Standardized mortality rates were estimated, and mortality‐related variables were identified using a Cox model.In all, 14,459 individuals constituted the full study population, including 6354 incident patients. In the incident population, 2199 (34.6%) were admitted to ICUs at least once, principally during the first year after the index date (N = 1477; 23.3%). This proportion decreased progressively to reach 3.0% in the seventh year. A total of 2817 patients received IVIg and 432 PE, again principally in the first year. In the full study population, the standardized mortality rate was 1.08 (95% confidence interval [CI] 1.03–1.13), being lower in men (0.95, 95% CI 0.89–1.02) than in women (1.15, 95% CI 1.07–1.23) and in patients aged >65 years (1.06, 95% CI 1.01–1.11) than in younger patients (1.50, 95% CI 1.24–1.76). Male gender, older age and higher comorbidity were independently associated with mortality.A subgroup of patients with MG require ICU admission and rescue therapy with IVIg or PE, indicative of poor disease control. New therapies are needed to improve disease control and reduce disease burden. [ABSTRACT FROM AUTHOR]

Introduction Aim Materials and methods Results Conclusion The severity of Von Willebrand disease (VWD) is currently based on laboratory phenotype. However, little is known about the severity of the patient's experience with the disease. The most recent VWD guidelines highlight the need for patient‐reported outcomes (PROs) in VWD.The study aimed to investigate the patient‐perspective on VWD severity and to identify key factors that determine the severity of disease experienced by patients.Patients participated in a nationwide cross‐sectional study on VWD in the Netherlands (WiN‐study). Patients filled in a questionnaire containing questions on the experienced severity of VWD (4‐point scale), bleeding score (BS) and quality of life (QoL).We included 736 patients, median age of 41.0 years (IQR 23.0–55.0) and 59.5% were women. A total of 443 had type 1, 269 type 2 and 24 type 3 VWD. Self‐reported severity of VWD was categorized as severe (n = 52), moderate (n = 171), mild (n = 393) or negligible (n = 120). Classification by historically lowest FVIII:C levels < 0.20 IU/mL as a proxy for severe VWD aligned with patient‐reported severity classification with a 72% accuracy. Type 3 VWD (OR = 4.02, 95%CI: 1.72–9.45), higher BS (OR = 1.09, 95%CI: 1.06–1.11), female sex (OR = 1.36, 95%CI: 1.01–1.83), haemostatic treatment in the year preceding study inclusion (OR = 1.53, 95%CI: 1.10–2.13) and historically lowest VWF:Act levels (OR = 0.26, 95%CI: 0.07–1.00) were independent determinants of patient‐reported severity.This study shows that patient‐reported data provide novel insights into the determinants of experienced disease severity. Our findings highlight the need for studies on PROs with validated questionnaires to assess the burden of VWD. [ABSTRACT FROM AUTHOR]

Background: Social comparison, the process of evaluating one's characteristics in relation to others, influences individuals' self‐perception and behavior. However, instruments are scarce for assessing social comparison in the medical setting. Objectives: Our aim was to develop and validate a new scale for assessing social comparison. Materials and methods: Seven statements were developed, encompassing the perceived normality of having rashes, the tendency to compare their situation with others, and the emotional response when seeing someone better or worse off than themselves. The instrument was piloted in 15 patients for readability and face validity, then prospectively validated using modern psychometric methods in 1,053 adult patients with eczema or psoriasis from three tertiary dermatological centers in Singapore. Results: Of 1,053 adult patients, 802 (76.2%) had eczema, and 251 (23.8%) had psoriasis. Exploratory factor analysis (using a 70% sample split) showed a single factor model comprising three questions (Eigenvalue: 1.4). Confirmatory factor analysis with the remaining 30% of the sample confirmed an excellent model fit. Cronbach's alpha was 0.7, and inter‐item correlations ranged from 0.42 to 0.46. In the Rasch analysis, item fit statistics and item characteristic curves showed appropriate discrimination between response options, although reliability was suboptimal with a person separation reliability of 0.63. Conclusions: Comprising 3 questions, the newly derived social comparison scale showed acceptable psychometrics as a measure of social comparison for clinical and research purposes in dermatology. Its brief nature likely results from its brevity and applicability to conditions beyond eczema and psoriasis, which warrants further investigation. [ABSTRACT FROM AUTHOR]

Ustilago maydis, the fungus that causes corn smut disease, leads to significant economic losses in maize cultivars. A key feature of successful plant pathogens is their ability to utilize the plant–pathogen relationship to influence disease progression. Greenhouse experiments examined how pollination and plant genotype affect disease incidence and severity of U. maydis infection. Four U. maydis susceptible maize inbreds (B73, H95, Mo17, and Golden Bantam), and two U. maydis resistant maize‐teosinte near‐isogenic lines (NIL1 and NIL2) were utilized for this work. Three‐hundred and sixty plants (pollinated and unpollinated) from the six plant genotypes were inoculated with U. maydis and assessed based on five phenotypic traits [(1) disease incidence, (2) gall number, (3) gall weight, (4) disease severity, and (5) area under disease progress curve]. All pollinated plants demonstrated significantly (p <.001) lower disease incidence, gall number, gall weight, area under the disease progress curve, and severity in comparison to the unpollinated plants. Both pollinated resistant NILs demonstrated significantly (p <.001) less disease development than the pollinated susceptible maize plants and two unpollinated NILs. Therefore, disease resistance to U. maydis was dependent upon pollination and plant genotype. This provides novel evidence that pollination can significantly improve resistance to U. maydis in different plant genotypes. Enhanced disease resistance observed in the resistant NILs after pollination indicates pollination‐mediated resistance is one of the resistance mechanisms functioning in the resistant NILs. Integration of pollination‐mediated resistance and resistance introgressed from a maize progenitor will be useful for improving resistance to U. maydis and management of the disease. [ABSTRACT FROM AUTHOR]

The relationship between peripheral inflammatory markers, their dynamic changes, and the disease severity of myasthenia gravis (MG) is still not fully understood. Besides, the possibility of using it to predict the short‐term poor outcome of MG patients have not been demonstrated. This study aims to investigate the relationship between peripheral inflammatory markers and their dynamic changes with Myasthenia Gravis Foundation of America (MGFA) classification (primary outcome) and predict the short‐term poor outcome (secondary outcome) in MG patients. The study retrospectively enrolled 154 MG patients from June 2016 to December 2021. The logistic regression was used to investigate the relationship of inflammatory markers with MGFA classification and determine the factors for model construction presented in a nomogram. Finally, net reclassification improvement (NRI) and integrated discrimination improvement (IDI) were utilized to evaluate the incremental capacity. Logistic regression revealed significant associations between neutrophil‐to‐lymphocyte ratio (NLR), platelet‐to‐lymphocyte ratio (PLR), aggregate index of systemic inflammation (AISI) and MGFA classification (p = 0.013, p = 0.032, p = 0.017, respectively). Incorporating dynamic changes of inflammatory markers into multivariable models improved their discriminatory capacity of disease severity, with significant improvements observed for NLR, systemic immune‐inflammation index (SII) and AISI in NRI and IDI. Additionally, AISI was statistically associated with short‐term poor outcome and a prediction model incorporating dynamic changes of inflammatory markers was constructed with the area under curve (AUC) of 0.953, presented in a nomograph. The inflammatory markers demonstrate significant associations with disease severity and AISI could be regarded as a possible and easily available predictive biomarker for short‐term poor outcome in MG patients. [ABSTRACT FROM AUTHOR]

In Peninsular Malaysia, Colletotrichum fioriniae, Colletotrichumfructicola, Colletotrichumscovillei, Colletotrichumsiamense and Colletotrichumtruncatum 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 Capsicumfrutescens. 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. [ABSTRACT FROM AUTHOR]

Key points: PVP‐I is a widely used antiseptic but only recently proposed for intranasal use.The extent of iodine absorption from available PVP‐I nasal products is unknown.Iodine absorption from use of Nasodine (0.5% PVP‐I nasal spray) is not clinically significant. [ABSTRACT FROM AUTHOR]

Rhinoviruses (RVs) are a leading cause of acute respiratory infections (ARI) in children. The relationship between RV viral loads (VL), RV/viral‐co‐detections and disease severity, is incompletely understood. We studied children and adolescents ≤21 years with RV‐ARI that were identified as inpatients or outpatients using a PCR panel from 2011‐2013. RV VL were stratified according to cycle threshold (CT) values in high (≤25), intermediate (26‐32) and low (>32). Adjusted analyses were performed to assess the role RV VL and RV/viral codetections on hospital admission, oxygen requirement, PICU care, and length of stay. Of 1,899 children with RV‐ARI, 78% had chronic comorbidities and 24% RV/viral co‐detections. Single RV vs RV/viral co‐detections was associated with higher VL (24.74 vs 26.62 CT; p = 0.001) and older age (14.9 vs 9.5 months; p = 0.0001). Frequency of RV/viral co‐detections were inversely proportional to RV loads: 32% with low; 28% with intermediate, and 19% with high VL, p = 0.0001. Underlying conditions were independently associated with all clinical outcomes, high VL with PICU care, and single RV‐ARI with higher odds of hospitalization. In summary, single RV vs RV/viral co‐detections were associated with higher VL and older age. Underlying diseases, rather than RV loads or RV/viral co‐detections, consistently predicted worse clinical outcomes. [ABSTRACT FROM AUTHOR]

Objective: Socioeconomic status (SES) is linked to health outcomes but has not been well studied in patients with chronic rhinosinusitis (CRS). The area deprivation index (ADI) is a comprehensive measure of geographic SES that ranks neighborhood disadvantage. This investigation used ADI to understand the impact of neighborhood disadvantage on CRS treatment outcomes. Methods: A total of 642 study participants with CRS were prospectively enrolled and self‐selected endoscopic sinus surgery (ESS) or continued appropriate medical therapy as treatment. The 22‐item SinoNasal Outcome Test (SNOT‐22) and Medical Outcomes Study Questionnaire Short‐Form 6‐D (SF‐6D) health utility value scores were recorded pre‐ and post‐treatment. Using residence zip codes, national ADI scores were retrospectively assigned to patients. Spearman's correlation coefficients (Rs) and Cramer's V effect size (φc) with 95% confidence interval (CI) were calculated. Results: A history of ESS was associated with significantly worse ADI scores compared to no history of ESS (φc = 0.18; 95% CI: 0.10, 0.25; p < 0.001). Baseline total SNOT‐22 (Rs = 0.14; 95% CI: 0.06, 0.22; p < 0.001) and SF‐6D values (Rs = −0.20; 95% CI: −0.27, −0.12; p < 0.001) were significantly negatively correlated with national ADI rank. No significant correlations between ADI and within‐subject improvement, or achievement of >1 minimal clinically important difference, in SNOT‐22 or SF‐6D scores after treatment were found. Conclusions: Geographic socioeconomic deprivation was associated with worse baseline disease severity and history of prior surgical intervention. However, ADI did not correlate with improvement in disease‐specific outcomes. The impact of socioeconomic deprivation on outcomes in CRS requires further investigation. [ABSTRACT FROM AUTHOR]

Fusarium incarnatum‐equiseti species complex infects a wide variety of food crops. Six fungal isolates were isolated from rotted roots of Dolichos lablab (hyacinth bean), Trichosanthes dioica (pointed gourd), Momordica dioica (spiny gourd), Capsicum frutescens (chilli) and Pisum sativum (garden pea), and identified as Fusarium spp., belonging to Fusarium incarnatum‐equiseti species complex (FIESC), through conidial morphology, sporodochia on carnation leaf agar medium and sequencing of nuclear ITS‐rRNA and transcription elongation factor 1α gene. Multilocus phylogenetic analysis demonstrated their inclusion within the Incarnatum clade of FIESC. All of them were self‐incompatible and failed to pair with other isolates. Vegetative incompatibility affected their pathogenicity and host specificity. The isolates secreted extracellular cell wall degrading enzymes cellulase (0.033 ± 0.002–0.403 ± 0.020 U.mL−1), polygalacturonase (0.005 ± 0.0001–0.392 ± 0.010 U.mL−1) and pectin‐lyase (0.015 ± 0.001–0.407 ± 0.012 U.mL−1) for direct penetration to root tissue. They also secreted toxic metabolites that inhibited germination of Cicer arietium (chickpea) and Pisum sativum (garden pea) seeds. The isolates exhibited complete pathogenicity on their original hosts (death due to root rotting, Disease Severity Index‐ 100%) but less pathogenicity in other non‐host plants (yellowing of lower leaves without sign of root rot, Disease Severity Index‐ <20%). This study reported the production of plant cell wall degrading enzymes and toxic metabolites by some pathogens belonging to FIESC and three new hosts of the pathogen such as hyacinth bean, spiny gourd and garden pea, from the Indian subcontinent. [ABSTRACT FROM AUTHOR]

Objective: The present study evaluated the oral tissue expression of micro‐RNA (miRNAs) linked to the potential malignant evolution of oral lichen planus (OLP). Furthermore, the correlation between OLP severity and miRNAs expression was assessed, and possible predictors of miRNAs in OLP patients were identified. Methods: The present study enrolled 41 patients with OLP (median age 58 years) and 42 healthy controls (median age 59 years). In each patient, miRNA levels (miR‐7a‐3p,‐7a2‐3p,‐7a‐5p,‐21‐3p,‐21‐5p,‐100‐3p,‐100‐5p,‐125b‐2‐3p,‐125b‐5p,‐200b‐3p,‐200b‐5p) were assessed and analyzed through reverse transcription polymerase chain reaction. Clinical parameters and the eventual presence of OLP symptoms, signs, and disease severity scores in each patient were reported using an anamnestic questionnaire. Results: In comparison with healthy controls, OLP patients showed significantly higher miR‐7a‐3p,‐7a‐2‐3p,‐21‐3p, miR‐21‐5p and miR‐100‐5p levels (p < 0.05) and significantly lower miR‐125b‐2‐3p,‐125b‐5p,‐200b‐3p, and ‐200b‐5p levels (p < 0.05). Furthermore, OLP symptoms and signs and disease severity scores were significantly correlated and were also predictors of all analyzed miRNAs (p < 0.05). Conclusions: In comparison with healthy subjects, OLP patients exhibited unbalanced oral miRNAs expression linked to the risk of potential malignant evolution of OLP. Furthermore, some miRNAs were correlated with OLP extent and were significant predictors of OLP symptoms, signs, and disease severity scores. [ABSTRACT FROM AUTHOR]

Background: Caused by duplications of the gene encoding peripheral myelin protein 22 (PMP22), Charcot–Marie–Tooth disease type 1A (CMT1A) is the most common hereditary neuropathy. Despite this shared genetic origin, there is considerable variability in clinical severity. It is hypothesized that genetic modifiers contribute to this heterogeneity, the identification of which may reveal novel therapeutic targets. In this study, we present a comprehensive analysis of clinical examination results from 1564 CMT1A patients sourced from a prospective natural history study conducted by the RDCRN‐INC (Inherited Neuropathy Consortium). Our primary objective is to delineate extreme phenotype profiles (mild and severe) within this patient cohort, thereby enhancing our ability to detect genetic modifiers with large effects. Methods: We have conducted large‐scale statistical analyses of the RDCRN‐INC database to characterize CMT1A severity across multiple metrics. Results: We defined patients below the 10th (mild) and above the 90th (severe) percentiles of age‐normalized disease severity based on the CMT Examination Score V2 and foot dorsiflexion strength (MRC scale). Based on extreme phenotype categories, we defined a statistically justified recruitment strategy, which we propose to use in future modifier studies. Interpretation: Leveraging whole genome sequencing with base pair resolution, a future genetic modifier evaluation will include single nucleotide association, gene burden tests, and structural variant analysis. The present work not only provides insight into the severity and course of CMT1A, but also elucidates the statistical foundation and practical considerations for a cost‐efficient and straightforward patient enrollment strategy that we intend to conduct on additional patients recruited globally. [ABSTRACT FROM AUTHOR]

Cervical cancer is the fourth most common cancer in women worldwide and is caused by persistent infection with high‐risk types of human papillomavirus (HPV). HPV viral load, the amount of HPV DNA in a sample, has been suggested to correlate with cervical disease severity, and with clinical outcome of cervical cancer. In this systematic review, we searched three databases (EMBASE, PubMed, Web of Science) to examine the current evidence on the association between HPV viral load in cervical samples and disease severity, as well as clinical outcome. After exclusion of articles not on HPV, cervical cancer, or containing clinical outcomes, 85 original studies involving 173 746 women were included. The vast majority (73/85 = 85.9%) reported that a higher viral load was correlated with higher disease severity or worse clinical outcome. Several studies reported either no correlation (3/85 = 3.5%), or the opposite correlation (9/85 = 10.6%); possible reasons being different categorization of HPV viral load levels, or the use of specific sampling methods. Despite variations in study design and populations, the above findings suggest that HPV viral load is correlated to clinical outcome, and may become an important biomarker for treatment selection and response monitoring for cervical cancer. [ABSTRACT FROM AUTHOR]

Although a range of blood traits have been reported to be associated with influenza A(H1N1)pdm09 (H1N1pdm09) disease severity, their underlying causal relationships and biological mechanisms have remained unclear. This study aimed to investigate the causal relationship between blood traits and H1N1pdm09 using a two‐sample Mendelian randomization analysis. Based on the data from our in‐house genome‐wide association study (GWAS) on H1N1pdm09 disease severity (Ncase [severe] = 70, Ncontrol [mild] = 95) and GWAS summaries of 44 blood traits from Biobank Japan (N = 12 303–143 658), we identified the potential causal effect of blood traits on severe H1N1pdm09. The inverse variance weighted method analysis revealed significant causal effects of lower aspartate aminotransferase (AST, β = −3.212, p = 0.019), low‐density‐lipoprotein cholesterol (LDL‐C, β = −1.372, p = 0.045), and basophil counts (Baso, β = −1.638, p = 0.047) on severe H1N1pdm09 disease. Additionally, polygenic risk score analysis further confirmed genetic overlap between these blood traits and severe H1N1pdm09 disease. This study provided evidence linking the lower level of AST, LDL‐C, and lower count of Baso with severe H1N1pdm09 disease, potentially identifying new therapeutic targets for patients with severe influenza. [ABSTRACT FROM AUTHOR]

Key Points Eosinophilic granulocytes have characteristic morphological features. This makes them prime candidates for utilization of a single cell binary classification network. Single cell binary classification networks can reliably help quantify eosinophils in nasal polyps. [ABSTRACT FROM AUTHOR]

Background: Chemokine‐like factor 1 (CKLF1) may be involved in the inflammatory response and secondary brain injury after severe traumatic brain injury (sTBI). We determined serum CKLF1 levels of sTBI patients to further investigate the correlation of CKLF1 levels with disease severity, functional prognosis, and 180‐day mortality of sTBI. Methods: Serum CKLF1 levels were measured at admission in 119 sTBI patients and at entry into study in 119 healthy controls. Serum CKLF levels of 50 patients were also quantified at days 1–3, 5, and 7 after admission. Glasgow coma scale (GCS) scores and Rotterdam computerized tomography (CT) classification were utilized to assess disease severity. Extended Glasgow outcome scale (GOSE) scores were recorded to evaluate function prognosis at 180 days after sTBI. Relations of serum CKLF1 levels to 180‐day poor prognosis (GOSE scores of 1–4) and 180‐day mortality were analyzed using univariate analysis, followed by multivariate analysis. Receiver‐operating characteristic (ROC) curve was built to investigate prognostic predictive capability. Results: Serum CKLF1 levels of sTBI patients increased at admission, peaked at day 2, and then gradually decreased; they were significantly higher during the 7 days after sTBI than in healthy controls. Differences of areas under ROC curve (areas under the curve [AUCs]) were not significant among the six time points. Multivariate analysis showed that serum CKLF1 levels were independently correlated with GCS scores, Rotterdam CT classification, and GOSE scores. Serum CKLF1 levels were significantly higher in non‐survivors than in survivors and in poor prognosis patients than in good prognosis patients. Serum CKLF1 levels independently predicted 180‐day poor prognosis and 180‐day mortality, and had high 180‐day prognosis and mortality predictive abilities, and their AUCs were similar to those of GCS scores and Rotterdam CT classification. Combination model containing serum CKLF1, GCS scores, and Rotterdam CT classification performed more efficiently than any of them alone in predicting mortality and poor prognosis. The models were visually described using nomograms, which were comparatively stable under calibration curve and were relatively of clinical benefit under decision curve. Conclusion: Serum CKLF1 levels are significantly associated with disease severity, poor 180‐day prognosis, and 180‐day mortality in sTBI patients. Hence, complement CKLF1 may serve as a potential prognostic biomarker of sTBI. [ABSTRACT FROM AUTHOR]

Background: In horses with trigeminal‐mediated headshaking (TMHS), clinical signs are likely to be expression of neuropathic facial pain. Currently, subjective assessment of disease severity is used as measure of compromise of animal's welfare. Objectives: To develop and validate a precise scoring system for TMHS: History, Rest and Exercise Score (HRE‐S). The HRE‐S consists of three subscores: history score (H‐S), resting score (R‐S) and exercise score (E‐S). Study design: Retrospective observational study. Methods: Seven masked observers with different experience used HRE‐S to score 40 video recordings taken during rest and lungeing including five duplicates. Video recordings were taken from nine horses with TMHS and three controls. Inter‐ and intraobserver reliability and practicability of HRE‐S were assessed. For every video recording severity of clinical signs was graded by every observer using an intuitive global‐type‐scale and interobserver reliability was calculated. Convergent validity was evaluated comparing HRE‐S to groups created by an existing score (grade 0–3). Discriminant validity was analysed comparing HRE‐S to groups created by intuitive global‐type‐scale. Results: Reliability for HRE‐S was excellent, irrespective of observers experience: Spearman's Rho = 0.946, p < 0.001 (intraobserver reliability) and intraclass correlation coefficient = 0.98, p < 0.001 (interobserver reliability). Interobserver reliability for intuitive global‐type‐scale was fair to substantial: Fleiss' κappa = 0.48 (R‐S) −0.63 (E‐S). Groups created by intuitive global‐type‐scale had significantly different R‐S and E‐S (p < 0.05), demonstrating discriminant validity. Convergent validity was proven as horses with grade 3/3 had significantly higher average E‐S and total scores compared with an existing score than those with grade 0/3 or 1/3 (p < 0.001). Main limitations: Retrospective nature, video recordings, sample size. Conclusions: HRE‐S is a valid and reliable score evaluating disease severity in TMHS, independent of observers' experience. [ABSTRACT FROM AUTHOR]

Objective: We aimed to investigate the value of individual laboratory tests and combinations of tests for predicting disease severity. Methods: We retrospectively reviewed 62 patients with space infections in the oral and maxillofacial head and neck regions. Patients were divided into three groups according to severity. Laboratory tests associated with disease severity were identified. Results: As the severity of infection increased, leukocytes, neutrophils, C‐reactive protein (CRP), procalcitonin (PCT), soluble interleukin receptor (sILR) 2, IL6, and creatinine (CR) increased. In the ROC analysis of group 1 (moderate infection) versus group 2 (severe infection), the area under the curve (AUC) values for leukocytes (AUC = 0.724), neutrophils (AUC = 0.714), PCT (AUC = 0.762) and a combination of the 3 tests (AUC = 0.768) suggested a strong predictive value. Furthermore, in the ROC analysis of group 2 (severe infection) versus group 3 (extremely severe infection), the AUC values for CRP (AUC = 0.84), PCT (AUC = 0.799), sIL2R (AUC = 0.937), IL6 (AUC = 0.863) and a combination of the four tests (AUC = 0.943) suggested a strong predictive value. Conclusions: Leukocytes, neutrophils, and PCT were associated with multispace infection and high severity. CRP, PCT, sIL2R, and/or IL6 were associated with extremely severe infections occurring in the oral and maxillofacial head and neck regions. [ABSTRACT FROM AUTHOR]

Background: Cognitive changes in Huntington's disease (HD) precede motor manifestations. ENROLL‐HD platform includes four cognitive measures of information processing speed (IPS). Our group is eager to seek clinical markers in the life stage that is as close as possible to the age of onset (ie, the so called prodromal HD phase) because this is the best time for therapeutic interventions. Objectives: Our study aimed to test whether cognitive scores in prodromal ENROLL‐HD mutation carriers show the potential to predict the severity of motor and behavioral changes once HD became fully manifested. Methods: From the global ENROLL‐HD cohort of 21,343 participants, we first selected a premanifest Cohort#1 (ie, subjects with Total Motor Score (TMS) <10 and Diagnostic Confidence Level (DCL) <4, N = 1.222). From this cohort, we then focused on a prodromal Cohort#2 of subjects who were ascertained to phenoconvert into manifest HD at follow‐up visits (ie, subjects from 6 ≤ TMS≤9 and DCL <4 to TMS≥10 and DCL = 4, n = 206). Results: The main results of our study showed that low IPS before phenoconversion in Cohort#2 predicted the severity of motor and behavioral manifestations. By combining the four IPS cognitive measures (eg, the Categorical Verbal Fluency Test; Stroop Color Naming Test; Stroop Word Reading; Symbol Digit Modalities Test), we generated a Composite Cognition Score (CCS). The lower the CCS score the higher the TMS and the apathy scores in the same longitudinally followed‐up patients after phenoconversion. Conclusions: CCS might represent a clinical instrument to predict the prognosis of mutation carriers who are close to manifesting HD. [ABSTRACT FROM AUTHOR]

Mycoplasma pneumoniae is a significant contributor to lower respiratory infections in children. However, the lipidomics and metabolics bases of childhood M. pneumoniae infections remain unclear. In this study, lipidomics and metabolomics analyses were conducted using UHPLC‐LTQ‐Orbitrap XL mass spectrometry and gas chromatography‐triple quadrupole mass spectrometry on plasma (n = 65) and urine (n = 65) samples. MS‐DIAL software, in combination with LipidBlast and Fiehn BinBase DB, identified 163 lipids and 104 metabolites in plasma samples, as well as 208 metabolites in urine samples. Perturbed lipid species (adjusted p < 0.05) were observed, including lysophosphatidylethanolamines, phosphatidylinositols, phosphatidylcholines, phosphatidylethanol amines, and triglycerides. Additionally, differential metabolites (adjusted p < 0.05) exhibited associations with amino acid metabolism, nucleotide metabolism, and energy metabolism. Thirteen plasma metabolites, namely l‐hydroxyproline, 3‐phosphoglycerate, citric acid, creatine, inosine, ribitol, α tocopherol, cholesterol, cystine, serine, uric acid, tagatose, and glycine, showed significant associations with disease severity (p < 0.05) and exhibited distinct separation patterns in M. pneumoniae–infected bronchitis and pneumonia, with an area under the curve of 0.927. Nine of them exhibited either positive or negative correlations with neutrophil or lymphocyte percentages. These findings indicated significant systemic metabolic shifts in childhood M. pneumoniae infections, offering valuable insights into the associated metabolic alterations and their relationship with disease severity. [ABSTRACT FROM AUTHOR]

Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a rare and severe adverse drug reaction involving multiple organs. Data on DRESS syndrome among children are currently limited. The purpose of this study was to determine the clinical features, causative drugs, systemic organ involvement, laboratory findings, disease severity score, and treatment outcomes in pediatric DRESS patients. The medical records of all pediatric DRESS patients, based on the RegiSCAR diagnostic criteria and admitted to King Chulalongkorn Memorial Hospital, Bangkok, Thailand from January 2010 to December 2021, were reviewed. Twenty‐two cases were identified (males 54.5%) with a median age of 9.5 years. Anticonvulsants (54.5%) and antibiotics (27.3%) were the leading culprit drugs. Skin rash was reported in all cases, followed closely by liver involvement (95.5%). Eosinophilia and atypical lymphocytosis were identified in 54.5% and 31.8% of cases, respectively. The median latency period was 17.5 days. Liver enzyme elevation was detected at an average onset of 20.0 days and hepatocellular type was the most common pattern of liver injury. Nineteen patients (86.4%) were treated with systemic corticosteroids with prednisolone being the most prescribed medication. One case developed Graves' disease after DRESS and multiple relapses of DRESS. One case (4.5%) died due to refractory status epilepticus that was unrelated to DRESS. Anticonvulsants were the major cause of DRESS in pediatric patients. High suspicion for DRESS is crucial in patients receiving these drugs and presenting with fever, rash, and internal organ involvement. [ABSTRACT FROM AUTHOR]

Serum amyloid A (SAA) is a clinically useful inflammatory marker involved in the pathogenesis of autoimmune diseases. This study aimed to explore the SAA levels in a cohort of patients with myasthenia gravis (MG) in relation to disease‐related clinical parameters and myasthenic crisis (MC) and elucidate the effects of SAA on immune response. A total of 82 MG patients including 50 new‐onset MG patients and 32 MC patients were enrolled in this study. Baseline data and laboratory parameters of all enrolled MG patients were routinely recorded through electronic medical systems. SAA levels were measured by enzyme‐linked immunosorbent assay (ELISA) kit. CD4+ T and CD19+ B cell subsets were analyzed by flow cytometry. In vitro, human recombinant SAA (Apo‐SAA) was applied to stimulate peripheral blood mononuclear cells (PBMCs) from MG patients to observe the effect on T and B cell differentiation. Our results indicated that SAA levels in new‐onset MG patients were higher than those in controls and were positively correlated with QMG score, MGFA classification, plasmablast cells, IL‐6, and IL‐17 levels. Subgroup analysis revealed that SAA levels were increased in generalized MG (GMG) patients than in ocular MG (OMG), as well as elevated in late‐onset MG (LOMG) than in early‐onset MG (EOMG) and higher in MGFA III/IV compared with MGFA I/II. The ROC curve demonstrated that SAA showed good diagnostic value for MC, especially when combined with NLR. In vitro, Apo‐SAA promoted the Th1 cells, Th17 cells, plasmablast cells, and plasma cells differentiation in MG PBMCs. The present findings suggested that SAA was increased in MG patients and promoted expansion of CD4+ T cell and CD19+ B cell subsets, which implicated in the severity of MG patients. [ABSTRACT FROM AUTHOR]

Background and purpose: Multiple system atrophy (MSA) is a neurodegenerative disease with characteristic motor and autonomic symptoms. Impaired brain serotonergic innervation can be associated with various clinical indices of MSA; however, the relationship between clinical symptoms and cerebrospinal fluid (CSF) levels of 5‐hydroxyindole acetic acid (5‐HIAA), a main serotonin metabolite, has not been fully elucidated. Methods: To compare CSF 5‐HIAA levels between patients with MSA and healthy controls, we included 33 controls and 69 MSA patients with either predominant parkinsonian or cerebellar ataxia subtypes. CSF 5‐HIAA levels were measured using high‐performance liquid chromatography. Additionally, we investigated correlations between CSF 5‐HIAA and various clinical indices in 34 MSA patients. Results: CSF 5‐HIAA levels were significantly lower in MSA patients than in controls (p < 0.0001). Probable MSA patients had lower CSF 5‐HIAA levels than possible MSA patients (p < 0.001). In MSA patients, CSF 5‐HIAA levels were inversely correlated with scores in Parts 1, 2, and 4 of the Unified Multiple System Atrophy Rating Scale, and with systolic and diastolic blood pressure in Part 3. Structural equation modeling revealed significant paths between serotonin and clinical symptoms, and significance was highest for activities of daily living, walking, and body sway. Conclusions: Serotonin dysfunction, as assessed by CSF 5‐HIAA levels, may implicate greater MSA severity. [ABSTRACT FROM AUTHOR]

Background: In addition to the elimination diet, dietary composition may influence disease severity in patients with eosinophilic esophagitis (EoE) through modulation of the immune response. Aim: To explore the immunomodulatory role of nutrition before and during elimination diet in adult EoE patients. Methods: Nutritional intake was assessed in 39 Dutch adult EoE patients participating in the Supplemental Elemental Trial (Dutch trial registry NL6014, NTR6778) using 3‐day food diaries. In this randomized controlled trial, diagnosed patients received either a four‐food elimination diet alone (FFED) or FFED with addition of an amino acid‐based formula for 6 weeks. Multiple linear regression analyses were performed to assess associations between the intake of nutrients and food groups per 1000 kCal and peak eosinophil count/high power field (PEC), both at baseline and after 6 weeks. Results: At baseline, we found a statistically significant negative (thus favorable) relationship between the intake of protein, total fat, phosphorus, zinc, vitamin B12, folate, and milk products and PEC (p <.05), while calcium (p =.058) and full‐fat cheese/curd (p =.056) were borderline (favorably) significant. In contrast, total carbohydrates, prepacked fruit juice, and white bread were significantly positively (unfavorable) related to PEC (p <.05), while ultra‐processed meals (p =.059) were borderline (unfavorably) significant. After dietary intervention, coffee/tea were significantly negatively (favorably) related to PEC, hummus/legumes were significantly positively (unfavorably) related with PEC, while peanuts were borderline significantly positively related (p =.058). Conclusion: Dietary composition may be related to inflammation in adult EoE patients. High‐quality and anti‐inflammatory diets may be a promising adjuvant therapy in the dietary management of EoE. [ABSTRACT FROM AUTHOR]

Background: Respiratory syncytial virus (RSV) infection is associated with significant morbidity in infants. Risk factors for severe disease beyond the first 2 years of life have not been fully defined. Methods: Children <5 years hospitalized with virologically confirmed RSV infection were identified over six respiratory seasons (10/2012–4/2018) and their medical records manually reviewed. Multivariable analyses were performed to define the age‐specific (<6, 6–24, and >24–59 months) risk factors associated with oxygen administration, PICU admission, mechanical ventilation, and duration of hospitalization. Results: We identified 5143 children hospitalized with RSV infection: 53.5% (n = 2749) <6 months; 31.7% (n = 1631) 6–24 months; and 14.8% (n = 763) >24–59 months. Rates of ICU admission were high (35%–36%) and comparable across age groups, while children >24–59 and 6–24 versus those <6 months required supplemental oxygen more frequently (73%; 71%; 68%, respectively; p =.003). The presence of comorbidities increased with age (25%, <6 months; 46%, 6–24 months; 70%, >24–59 months; p <.001). Specifically, neuromuscular disorders, chronic lung disease, and reactive airway disease/asthma were predictive of worse clinical outcomes in children aged 6–24 and >24–59 months, while RSV‐viral codetections increased the risk of severe outcomes in children aged <6 and 6–24 months of age. Conclusions: Almost half of children hospitalized with RSV infection were >6 months. Underlying comorbidities increased with age and remained associated with severe disease in older children, while RSV‐viral codetections were predictive of worse clinical outcomes in the youngest age groups. These data suggest the importance of defining the clinical phenotype associated with severe RSV according to age, and the persistent burden associated with RSV beyond infancy. [ABSTRACT FROM AUTHOR]

The neuroprotective effects of dietary patterns have been reported in previous studies. This study aimed to examine the association between the dietary approach to stop hypertension (DASH), the Mediterranean diet (MeDi), and the Mediterranean‐DASH intervention for neurodegenerative delay (MIND) with the severity and risk of Parkinson's disease (PD). In this comparative cross‐sectional study, 120 patients with PD and 50 healthy participants participated. Adherence to DASH, MeDi, and MIND dietary patterns was determined according to the dietary intake data using a food frequency questionnaire (FFQ). The Severity of PD was determined by the Unified Parkinson's Disease Rating Scale (UPDRS). The mean score of the DASH was significantly lower in the PD group compared to the healthy group (p =.006), but the mean score of MeDi and MIND did not significantly differ between the two groups (p >.05). Also, the mean score of the DASH was significantly lower in men than in women in the healthy group (p =.018). High adherence to the DASH diet decreased the risk of PD by 15% (OR = 0.856, 95% CI: 0.751, 0.976, p =.020). Participants in quartiles 3 and 4 of the DASH dietary pattern had 86% (p =.003) and 87% (p =.007), respectively, lower risk of PD. MeDi and MIND diets were not significantly associated with the risk of PD. There was no significant association between dietary patterns and the severity of PD. The findings indicate that high adherence to the DASH dietary pattern may protect against PD. [ABSTRACT FROM AUTHOR]

Objective: The purpose of this study was to analyze barriers to medical care and follow‐up in patients with allergic fungal rhinosinusitis (AFRS). Study Design: Cross‐sectional questionnaire‐based study with retrospective chart review. Setting: Tertiary Medical Center. Methods: Subjects with AFRS and chronic rhinosinusitis with nasal polyps (CRSwNP) were prospectively recruited for completion of the Barriers to Care Questionnaire (BCQ) and formal chart review. Results: Fifty‐nine AFRS and 51 CRSwNP patients participated. AFRS patients were more likely to be lost to follow‐up within 6 months of surgery (35.6% vs 17.7%, P = 0.04) and no‐show at least 1 appointment (20.3% vs 5.9%, P = 0.03) compared to CRSwNP patients. Men with AFRS were more likely to have only a single follow‐up visit (37.0% vs 3.1%, P < 0.001) and be lost to follow‐up (66.7% vs 9.4%, P < 0.001) than women. There were no significant differences in the BCQ between groups; however, rate of questionnaire completion was lower in the AFRS group than the CRS group (62.7% vs 80.4%, P = 0.042). AFRS patients who did not complete the BCQ were more likely to be male (63.6% vs 35.1%, P = 0.034), lost to follow‐up (77.3% vs 10.8%, P < 0.0001), and have a single follow‐up visit (40.9% vs 5.4%, P < 0.0001). Younger age was associated with increased likelihood of having a single follow‐up visit (odds ratio 1.143, 95% CI 1.022‐1.276). Conclusion: Young, male AFRS patients are more frequently lost to follow‐up after surgery and less likely to complete questionnaires assessing barriers to care. Further investigation is needed to assess barriers to follow‐up in these at‐risk groups. [ABSTRACT FROM AUTHOR]

Background: Influenza is a substantial cause of annual morbidity and mortality; however, correctly identifying those patients at increased risk for severe disease is often challenging. Several severity indices have been developed; however, these scores have not been validated for use in patients with influenza. We evaluated the discrimination of three clinical disease severity scores in predicting severe influenza‐associated outcomes. Methods: We used data from the Influenza Hospitalization Surveillance Network to assess outcomes of patients hospitalized with influenza in the United States during the 2017–2018 influenza season. We computed patient scores at admission for three widely used disease severity scores: CURB‐65, Quick Sepsis‐Related Organ Failure Assessment (qSOFA), and the Pneumonia Severity Index (PSI). We then grouped patients with severe outcomes into four severity tiers, ranging from ICU admission to death, and calculated receiver operating characteristic (ROC) curves for each severity index in predicting these tiers of severe outcomes. Results: Among 8252 patients included in this study, we found that all tested severity scores had higher discrimination for more severe outcomes, including death, and poorer discrimination for less severe outcomes, such as ICU admission. We observed the highest discrimination for PSI against in‐hospital mortality, at 0.78. Conclusions: We observed low to moderate discrimination of all three scores in predicting severe outcomes among adults hospitalized with influenza. Given the substantial annual burden of influenza disease in the United States, identifying a prediction index for severe outcomes in adults requiring hospitalization with influenza would be beneficial for patient triage and clinical decision‐making. [ABSTRACT FROM AUTHOR]

Background: Although altered eicosanoid levels are related to disease severity in chronic rhinosinusitis with nasal polyps (CRSwNP), identifying patients prone to recurrent nasal polyps (NPs) is still difficult. We investigated levels of nasally secreted eicosanoids before and after NP surgery in patients with or without NP recurrence (NPR) and explored potential endotypes based on pre‐surgical eicosanoid levels. Methods: Levels of leukotriene (LT) E4, LTB4, prostaglandin (PG) D2, PGE2 and 15(S) hydroxyeicosatetraenoic acid (15[S]‐HETE) were measured in nasal secretions with specific immunoassays at pre‐surgery (n = 38) and 6 and 12 months post‐surgery (n = 35), with NPR identified endoscopically. Pre‐ and post‐surgical levels were compared between patients with and without NPR. Eicosanoid patterns among patients were explored with cluster analysis and evaluated with clinical parameters. Results: Patients with recurrent NPs had pronounced pre‐surgical levels of nasal 15(S)‐HETE, PGD2 and LTE4. From pre‐surgery to 12 months post‐surgery, NPR was associated with significant decreases of 15(S)‐HETE and PGD2 relative to non‐recurrence, whereas levels of LTE4 decreased at 6 months but increased again at 12 months. Clustering revealed three potential endotypes. Clusters 1 and 3 featured high and low eicosanoid levels, respectively. Cluster 2 had higher levels of LTE4 and PGD2, lower levels of PGE2 and LTB4, and more cases of recurrent NPs and previous NP surgeries. Conclusion: Elevated nasal LTE4 12 months post‐surgery in NP recurrent subjects suggests that postoperative LTE4 measurements may indicate rapid NP regrowth. A distinct nasal eicosanoid profile may be used for the identification of the most severe recalcitrant patients in need of targeted immunomodulatory therapies. [ABSTRACT FROM AUTHOR]

Dothistroma needle blight (DNB) is a serious needle disease of conifers that primarily affects pine species (Pinus spp.). Dothistroma septosporum is one of the DNB pathogens that has a diverse range of host species excluding Pinus armandii. In 15 inoculated P. armandii seedlings, D. septosporum acervuli were observed in 43 infected needles of ten seedlings with a mean disease severity of 1.11% at 25 weeks after inoculations, demonstrating the potential of D. septosporum to cause symptoms on the needles of P. armandii via artificial inoculation. The disease severity of P. armandii was similar to the positive control, Pinus nigra (median 0.75 for P. armandii to 0.70 for P. nigra), thus, P. armandii acts under artificial conditions as a susceptible host species. [ABSTRACT FROM AUTHOR]

Background: Few studies have evaluated mouth opening (MO) in systemic sclerosis (SSc). None have studied MO trajectories. Objective: To study MO trajectories in SSc. Methods: This multicentre study included patients enrolled in the French national SSc cohort with at least one MO assessment, described patients based on MO baseline measure, modelled MO trajectories and associated MO measures with SSc prognosis. Results: We included 1101 patients. Baseline MO was associated with disease severity. On Kaplan–Meier analysis, MO <30 mm was associated with worse 30‐year‐survival (p < 0.01) and risk of pulmonary arterial hypertension (p < 0.05). Individual MO trajectories were heterogenous among patients. The best model of MO trajectories according to latent‐process mixed modelling showed that 88.8% patients had a stable MO trajectory and clustered patients into three groups that predicted SSc survival (p < 0.05) and interstitial lung disease (ILD) occurrence (p < 0.05). The model highlighted a cluster of 9.5% patients with diffuse cutaneous SSc (dcSSc) (p < 0.05) and high but decreasing MO over 1 year (p < 0.0001) who were at increased risk of poor survival and ILD. Conclusion: MO, which is a simple and reliable measure, could be used to predict disease severity and survival in SSc. Although MO remained stable in most SSc patients, dcSSc patients with high but decreasing MO were at risk of poor survival and ILD. [ABSTRACT FROM AUTHOR]

Background and Aim: The clinical severity of acute pancreatitis is unpredictable, ranging from self‐limiting disease to life‐threatening inflammation. The determinants of severe acute pancreatitis (SAP) are unclear. We aim to identify clinical variables and single nucleotide polymorphisms (SNP) associated with SAP. Methods: We used UK Biobank data to conduct a case–control clinical and genetic association study. Pancreatitis patients were identified through national hospital and mortality records across the United Kingdom. Clinical covariates and SAP were analyzed for associations. Genotyped data that included 35 SNPs were assessed for independent associations with SAP and SNP to SNP interaction. Results: A total of 665 patients with SAP and 3304 non‐SAP patients were identified. Male sex and older age increased odds of developing SAP (odds ratio [OR] 1.48; 95% confiden interval [CI] 1.24–1.78, P < 0.0001) and (OR 1.23; 95% CI 1.17–1.29), P < 0.0001), respectively. SAP was associated with diabetes (OR 1.46; 95% CI 1.15–1.86, P = 0.002), chronic kidney disease (OR 1.74; 95% CI 1.26–2.42, P = 0.001), and cardiovascular disease (OR 2.00; 95% CI 1.54–2.61, P = 0.0001). A significant association was established between IL‐10 rs3024498 and SAP (OR 1.24; 95% CI 1.09–1.41, P = 0.0014). Epistasis analysis revealed that the odds of SAP was greater by an interaction between TLR 5 rs5744174 and Factor V rs6025 (ORinteraction 7.53; P = 6.64 × 10−5). Conclusion: This study reports clinical risk factors for SAP. We also show evidence for an interaction between rs5744174 and rs6025 as determinants for SAP in addition to rs3024498 independently altering the severity of acute pancreatitis. [ABSTRACT FROM AUTHOR]

Objective: This paper aimed to unveil the diagnostic values of serum brain natriuretic peptide (BNP), pentraxin 3 (PTX3), and vascular endothelial growth factor (VEGF) in acute pulmonary embolism complicated by pulmonary artery hypertension (APE‐PAH) and their correlations with severity of PAH. Methods: A total of 153 patients with APE were selected for our study and divided into the PAH and Non‐PAH groups according to the measurement of pulmonary artery pressure by echocardiography. Serum BNP levels were measured by chemiluminescence immunoassay, and serum PTX3 and VEGF levels were appraised by ELISA. The predictive values of BNP, PTX3, and VEGF for APE‐PAH were evaluated by applying the receiver operating characteristic (ROC) curve. Spearman test was implemented to correlate BNP, PTX3, and VEGF with the severity of PAH. Results: Higher serum levels of BNP, PTX3, and VEGF were observed in the PAH group versus the Non‐PAH group (p <.05). ROC curve analysis indicated that BNP, PTX3, and VEGF had acceptable diagnostic value for predicting APE‐PAH. Higher serum levels of BNP, PTX3, and VEGF were witnessed in the moderate and severe PAH groups in contrast to the mild PAH group (p <.05), and the levels of these parameters were elevated in the severe PAH group versus the moderate PAH group (p <.05). Spearman correlation analysis signified that serum BNP (r = 0.377), PTX3 (r = 0.488), and VEGF (r = 0.575) levels were positively correlated with the severity of PAH in APE‐PAH patients. Conclusion: Serum BNP, PTX3, and VEGF levels are significantly elevated in APE‐PAH patients. Serum BNP, PTX3, and VEGF levels are of clinical value in the diagnosis of APE‐PAH patients, and serum BNP, PTX3, and VEGF levels are positively correlated with the severity of PAH and can be used as predictors of the severity of PAH. [ABSTRACT FROM AUTHOR]

To further understand the role of NS1‐specific antibodies (Abs) in disease pathogenesis, we compared neutralizing antibody levels (Nabs), NS1‐Ab levels, IgG antibody subclass profiles and NS1‐specific memory B‐cell responses (Bmems) in individuals, with varying severity of past dengue. Nabs (Neut50 titres) were assessed using the Foci Reduction Neutralization Test (FRNT) and in‐house ELISAs were used to assess NS1‐Abs and NS1‐Ab subclasses for all four DENV serotypes in individuals with past DF (n = 22), those with past DHF (n = 14) and seronegative (SN) individuals (n = 7). B‐cell ELISpot assays were used to assess NS1‐specific Bmem responses. 15/22 (68.18%) individuals with past DF and 9/14 (64.29%) individuals with past DHF had heterotypic infections. Neut50 titres were found to be significantly higher for DENV1 than DENV2 (p = 0.0006) and DENV4 (p = 0.0127), in those with past DHF, whereas there was no significant difference seen in titres for different DENV serotypes in those with past DF. Overall NS1‐Ab to all serotypes and NS1‐specific IgG1 responses for DENV1, 2 and 4 serotypes were significantly higher in those with past DHF than individuals with past DF. Those with past DHF also had higher IgG1 than IgG3 for DENV1 and DENV3, whereas no differences were seen in those with past DF. Over 50% of those with past DF or DHF had NS1‐specific Bmem responses to >2 DENV serotypes. There was no difference in the frequency of Bmem responses to any of the DENV serotypes between individuals with past DF and DHF. Although the frequency of Bmem responses to DENV1 correlated with DENV1‐specific NS1‐Abs levels (Spearman r = 0.35, p = 0.02), there was no correlation with other DENV serotypes. We found that those with past DF had broadly cross‐reactive Nabs, while those with past DHF had higher NS1‐Ab responses possibly with a different functionality profile than those with past DF. Therefore, it would be important to further evaluate the functionality of NS1‐specific antibody and Bmem responses to find out the type of antibody repertoire that is associated with protection against severe disease. [ABSTRACT FROM AUTHOR]

The article "Response to 'Systemic correlates of cutaneous manifestations of lupus erythematosus'" explores the relationship between lupus erythematosus (LE) skin disease and systemic lupus erythematosus (SLE). The authors found that LE skin disease commonly occurs in patients with SLE but does not impact the development of severe SLE sequelae, the number of medications needed, or overall survival. The study suggests the importance of closely managing LE skin disease in patients with SLE and calls for further research to better understand the relationship between skin involvement and disease severity. [Extracted from the article]

Key points: Eustachian tube recanalization is a feasible procedure but additional studies are needed to determine its safety.Eustachian tube closure can result from different etiologies and can cause severe symptoms.Ureteral stents have appropriate shape and pliability for placement and long‐term healing.Multidisciplinary team approach allows for simultaneous endonasal and otologic approaches. [ABSTRACT FROM AUTHOR]

Background: The severity of Severe Acute Respiratory Syndrome Coronavirus 2 infection varies with age and time. Here, we quantify how age‐specific risks of hospitalization, intensive care unit (ICU) admission, and death upon infection changed from February 2020 to June 2021 in the Netherlands. Methods: A series of large representative serology surveys allowed us to estimate age‐specific numbers of infections in three epidemic periods (late‐February 2020 to mid‐June 2020, mid‐June 2020 to mid‐February 2021, and mid‐February 2021 to late‐June 2021). We accounted for reinfections and breakthrough infections. Severity measures were obtained by combining infection numbers with age‐specific numbers of hospitalization, ICU admission, and excess all‐cause deaths. Results: There was an accelerating, almost exponential, increase in severity with age in each period. The rate of increase with age was the highest for death and the lowest for hospitalization. In late‐February 2020 to mid‐June 2020, the overall risk of hospitalization upon infection was 1.5% (95% confidence interval [CI] 1.3–1.8%), the risk of ICU admission was 0.36% (95% CI: 0.31–0.42%), and the risk of death was 1.2% (95% CI: 1.0–1.4%). The risk of hospitalization was significantly increased in mid‐June 2020 to mid‐February 2021, while the risk of ICU admission remained stable over time. The risk of death decreased over time, with a significant drop among ≥70‐years‐olds in mid‐February 2021 to late‐June 2021; COVID‐19 vaccination started early January 2021. Conclusion: Whereas the increase in severity of Severe Acute Respiratory Syndrome Coronavirus 2 with age remained stable, the risk of death upon infection decreased over time. A significant drop in risk of death among elderly coincided with the introduction of COVID‐19 vaccination. [ABSTRACT FROM AUTHOR]

Introduction/Aims: Myasthenia gravis (MG) patients have been predicted to have high rates of coronavirus disease‐2019 (COVID‐19) complications due to frequent involvement of respiratory muscles in MG and frequent use of immunosuppressive therapies. We investigated outcomes of MG patients infected with SARS‐CoV‐2 to identify risk factors for exacerbation and severe disease. Methods: This was a retrospective analysis of 39 MG patients with SARS‐CoV‐2 infection from January March 1, 2020 to October 25, 2021 at Emory University. Patients' records were queried for demographic data, MG history, and COVID‐19 treatments and hospitalizations. Results: At the time of infection, 8 of 39 were vaccinated, 30 of 39 unvaccinated, and 1 unknown. Average age was 52.6 years. Twenty‐seven patients were receiving immunomodulatory treatments at the time of infection. Thirty‐five of 39 were symptomatic, 21 were hospitalized, and 7 required ventilations. MG exacerbations occurred in 5 and were treated with therapeutic plasma exchange (n = 1), intravenous immunoglobulin (IVIg) (n = 1), and prednisone taper (n = 5). Four hospitalized patients died from COVID‐related lung injuries. No deaths were attributed to MG exacerbation; however, one patient receiving IVIg for MG exacerbation had a pulmonary embolism. There were no deaths in fully vaccinated patients, and only one vaccinated patient was admitted to the intensive care unit. Discussion: High rates of COVID‐19 complications and death were observed in this cohort of MG patients. Some patients with MG and COVID‐19 also had an exacerbation during infection. Further studies are needed to determine whether MG patients are at higher risk for complications than the rest of the population. [ABSTRACT FROM AUTHOR]

Objective: To investigate DNA methylation (DNAm) status of dickkopf‐associated protein 1 (DKK‐1) in ossified hip capsule synovium and serum among patients with ankylosing spondylitis (AS). Methods: Western blot was applied to detect the level of DKK‐1 protein expression in hip joint capsule tissues from four patients with AS as well as four patients with femoral neck fracture (FNF) caused by trauma as control. DKK‐1 gene promoter methylation (GPM) was examined by methylation‐specific polymerase chain reaction. Reverse transcription‐polymerase chain reaction was performed to examine the messenger RNA (mRNA) levels of DKK‐1, β‐catenin, and Wnt3a in both tissue and serum. The DNAm status of serum DKK‐1 was measured among 36 patients with AS and syndesmophytes (AS + syndesmophytes group), 40 patients with AS but no syndesmophyte (AS group), and 42 healthy individuals (control group). Also, the serum levels of DKK‐1 were measured by enzyme‐linked immunosorbent assay. The modified New York criteria (mNYC) together with the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS) were adopted to examine the radiographic progression of AS. The receiver operating characteristic (ROC) curve was applied to investigate the diagnostic value of the methylation rate of DKK‐1 with regard to radiographic progression. Results: The expressions of DKK‐1 protein and mRNA in hip joint capsule tissues of AS patients were significantly lower, while DKK‐1 GPM rate, β‐catenin mRNA, and Wnt3a mRNA were markedly higher when compared with FNF group. For serum samples, the DKK‐1 methylation rate was significantly higher in AS+ syndesmophytes group in contrast to AS group and healthy controls. Serum levels of DKK‐1 protein and mRNA in AS with syndesmophytes group were markedly decreased, while β‐catenin mRNA and Wnt3a mRNA expressions were significantly increased than AS with no syndesmophyte group and the healthy control group. AS patients in Grade 4 showed a significantly higher serum DKK‐1 GPM rate than those in Grade 3 based on mNYC. Serum DKK‐1 GPM level was markedly and positively correlated with mSASSS. Serum levels of DKK‐1 in AS+ syndesmophytes group were markedly lower compared with AS but no syndesmophyte group and healthy controls. ROC curve analysis indicated that serum DKK‐1 methylation rate serves as a decent indicator for AS radiographic progression. Conclusion: DNAm of DKK‐1 may correlate with pathological bone formation in AS, which may provide new strategies for the treatment of AS abnormal bone formation. [ABSTRACT FROM AUTHOR]

Objective: Chronic spontaneous urticaria (CSU) has a profound impact on the sleep quality, productivity and overall quality of life of affected individuals. This study aimed to investigate the correlation between serum Th17/Treg immune dysregulation and the severity of CSU in patients. Methods: Clinical baseline data of 120 CSU patients and matched healthy controls were recorded. The pruritus level, disease severity, and quality of life of CSU patients were assessed using the visual analogue scale, weekly Urticaria Activity Score and chronic urticaria quality of life questionnaire, respectively. The Th17/Treg cell ratio was detected by flow cytometry. ELISA was used to measure the levels of serum Th17 cytokines (IL‐17, IL‐21) and Treg cytokines (TGF‐β1, IL‐35). Pearson's correlation analysis was conducted to examine the associations between these indicators. Results: No significant differences were identified in terms of sex, age, and BMI between the two groups. However, CSU patients exhibited a significant increase in the Th17 cell ratio, as well as the elevated serum levels of TGF‐β1, IL‐17 and, IL‐21. Conversely, the proportion of Treg cells and the levels of IL‐35 were remarkably decreased in CSU patients. Peripheral blood Th17 cells were negatively correlated with Treg cells. The severity of pruritus, life quality, and disease severity in CSU patients were positively correlated to Th17 cell ratio, and inversely correlated with Treg cell proportion. Conclusions: A positive correlation was found between the percentage of peripheral blood Th17 cell in CSU patients and the pruritus level, life quality, and disease severity. In constrast, there was a negative correlation between the proportion of peripheral blood Treg cells and these clinical parameters. [ABSTRACT FROM AUTHOR]

Myasthenia gravis (MG) is an antibody‐mediated autoimmune disorder characterized by fluctuation of fatigue and weakness of muscle. Due to the heterogeneity of the course of MG, available biomarkers for prognostic prediction are urgently needed. Ceramide (Cer) was reported to participate in immune regulation and many autoimmune diseases, but its effects on MG remain undefined. This study aimed to investigate the ceramides expression levels in MG patients and their potential as novel biomarkers of disease severity. Levels of plasma ceramides were determined by ultra performance liquid chromatography–tandem mass spectrometry (UPLC‐MS/MS). Severity of disease was assessed by quantitative MG scores (QMGs), MG‐specific activities of daily living scale (MG‐ADLs) and 15‐item MG quality of Life (MG‐QOL15). The concentrations of serum interleukin‐1β (IL‐1β), IL‐6, IL‐17A, and IL‐21 were determined by enzyme‐linked immunosorbent assay (ELISA), and the proportions of circulating memory B cells and plasmablasts were detected by flow‐cytometry assay. Four plasma ceramides levels we studied were detected higher in MG patients. And three of them (C16:0‐Cer, C18:0‐Cer, and C24:0‐Cer) were positively associated with QMGs. In addition, receiver operating characteristic (ROC) analysis suggested that plasma ceramides have a good ability of differentiating MG from HCs. Importantly, only C18:0‐Cer was shown to be positively associated with the concentration of serum IL and circulating memory B cells, and the decrease in plasma C18:0‐Cer paralleled the clinical improvement of patients with MG. All together, our data suggest that ceramides may play an important role in the immunopathological mechanism of MG, and C18:0‐Cer has the potential to be a novel biomarker for disease severity in MG. [ABSTRACT FROM AUTHOR]

Despite the higher transmissibility of Omicron Variant of Concern (VOC), several reports have suggested lower risk for hospitalization and severe outcomes compared to previous variants of SARS‐CoV‐2. This study, enrolling all COVID‐19 adults admitted to a reference hospital who underwent both the S‐gene‐target‐failure test and VOC identification by Sanger sequencing, aimed to describe the evolving prevalence of Delta and Omicron variants and to compare the main in‐hospital outcomes of severity, during a trimester (December 2021 to March 2022) of VOCs' cocirculation. Factors associated with clinical progression to noninvasive ventilation (NIV)/mechanical ventilation (MV)/death within 10 days and to MV/admission to intensive care unit (ICU)/death within 28 days, were investigated through multivariable logistic regressions. Overall, VOCs were: Delta n = 130/428, Omicron n = 298/428 (sublineages BA.1 n = 275 and BA.2 n = 23). Until mid‐February, Delta predominance shifted to BA.1, which was gradually displaced by BA.2 until mid‐March. Participants with Omicron VOC were more likely to be older, fully vaccinated, with multiple comorbidities and to have a shorter time from symptoms' onset, and less likely to have systemic symptoms and respiratory complications. Although the need of NIV within 10 days and MV within 28 days from hospitalization and the admission to ICU were less frequent for patients with Omicron compared to those with Delta infections, mortality was similar between the two VOCs. In the adjusted analysis, multiple comorbidities and a longer time from symptoms' onset predicted 10‐day clinical progression, while complete vaccination halved the risk. Multimorbidity was the only risk factor associated with 28‐day clinical progression. In our population, in the first trimester of 2022, Omicron rapidly displaced Delta in COVID‐19 hospitalized adults. Clinical profile and presentation differed between the two VOCs and, although Omicron infections showed a less severe clinical picture, no substantial differences for clinical progression were found. This finding suggests that any hospitalization, especially in more vulnerable individuals, may be at risk for severe progression, which is more related to the underlying frailty of patients than to the intrinsic severity of the viral variant. [ABSTRACT FROM AUTHOR]

Aim: To compare the clinical outcomes among women diagnosed with severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection during pregnancy, and their neonates, during the period when the Omicron variant predominated in Japan with those of the pre‐Omicron variant period. Methods: We conducted a retrospective single‐center cohort study between August 1, 2020, and June 30, 2022. The cohort was divided into pre‐Omicron group (August 1, 2020 to November 30, 2021) and Omicron group (December 1, 2021 to June 30, 2022). The primary outcome was maternal intensive care unit (ICU) admission during the perinatal period. The secondary outcomes were maternal oxygen administration before and after delivery, preterm birth (PTB), and low birth weight (LBW). Results: During the study period, 81 pregnant women were admitted to the hospital with SARS‐CoV‐2 infection (pre‐Omicron period, n = 28; Omicron period, n = 53). SARS‐CoV‐2 infection during the Omicron period was associated with lower risk of maternal ICU admission (adjusted‐odds ratio [aOR]: 0.10, 95% confidence interval [CI]: 0.01–1.23, p = 0.072), oxygen administration via a nasal cannula or mask (aOR: 0.18, 95% CI: 0.03–0.96, p = 0.045), PTB (aOR: 0.15, 95% CI: 0.04–0.51, p = 0.002), and LBW (aOR: 0.13, 95% CI: 0.03–0.55, p = 0.005). Conclusion: Among pregnant women, SARS‐CoV‐2 infection during the Omicron period was associated with reduced risk of maternal ICU admission, requiring supplemental oxygen, PTB, and LBW. This can be attributable to lower virulence of the Omicron variant and higher vaccination coverage during the Omicron period. [ABSTRACT FROM AUTHOR]

Hereditary transthyretin‐related (hATTR) amyloidosis is a rare disease, causing a disabling and life‐threatening axonal length‐dependent polyneuropathy. Monitoring of disease progression and treatment response is difficult. We aimed to determine if serum neurofilament light chain (sNfL) is a reliable and early biomarker of peripheral neuropathy in hATTR amyloidosis. We prospectively included 20 hATTR patients, 14 symptomatic and 6 asymptomatic. Patients were assessed at baseline and 1 year, including a full clinical examination with disease severity and functional scores, electrochemical skin conductance measurement with Sudoscan and nerve conduction studies, and sNfL level. hATTR patient sNfL were also compared with sNfL of 4532 healthy controls of a reference database by calculating age and BMI‐adjusted Z scores. At baseline, median sNfL concentration was 3.6‐fold higher in symptomatic than asymptomatic hATTR patients (P =.003), and this difference was also found in our under 60‐years‐old patients (P =.003). There was no significant difference of sNfL concentration between asymptomatic patients and healthy controls (Z‐score of −0.29), but a significant difference between symptomatic patients and healthy controls (Z‐score of 2.52). We found a significant correlation between sNfL levels and most clinical and electrophysiological disease severity scores, the strongest correlation being with the NIS score. sNfL seems to be a reliable biomarker of peripheral neuropathy severity in hATTR amyloidosis and can distinguish between asymptomatic and symptomatic patients. sNfL could also become a reliable biomarker to establish disease onset and treatment response. [ABSTRACT FROM AUTHOR]

Background: Patients are admitted to the hospital for respiratory illness at different stages of their disease course. It is important to appropriately analyse this heterogeneity in surveillance data to accurately measure disease severity among those hospitalized. The purpose of this study was to determine if unique baseline clusters of influenza patients exist and to examine the association between cluster membership and in‐hospital outcomes. Methods: Patients hospitalized with influenza at two hospitals in Southeast Michigan during the 2017/2018 (n = 242) and 2018/2019 (n = 115) influenza seasons were included. Physiologic and laboratory variables were collected for the first 24 h of the hospital stay. K‐medoids clustering was used to determine groups of individuals based on these values. Multivariable linear regression or Firth's logistic regression were used to examine the association between cluster membership and clinical outcomes. Results: Three clusters were selected for 2017/2018, mainly differentiated by blood glucose level. After adjustment, those in C171 had 5.6 times the odds of mechanical ventilator use than those in C172 (95% CI: 1.49, 21.1) and a significantly longer mean hospital length of stay than those in both C172 (mean 1.5 days longer, 95% CI: 0.2, 2.7) and C173 (mean 1.4 days longer, 95% CI: 0.3, 2.5). Similar results were seen between the two clusters selected for 2018/2019. Conclusion: In this study of hospitalized influenza patients, we show that distinct clusters with higher disease acuity can be identified and could be targeted for evaluations of vaccine and influenza antiviral effectiveness against disease attenuation. The association of higher disease acuity with glucose level merits evaluation. [ABSTRACT FROM AUTHOR]

Introduction: Sinus infections are a common reason patients seek medical care. However, the intended meaning of the term sinus infection among patients and otolaryngologists is incompletely understood. Methods: In this multi‐institutional cross‐sectional study, a semantics‐based questionnaire was provided to consecutive patients presenting to otolaryngology clinics at six academic centers from June 2020 until May 2021. The primary outcome was respondent definitions for sinus infection from a list of 28 proposed terms covering six general categories. Secondary outcome measures included differences between geographic regions. Results: Responses were obtained from 560 patients (54% female, mean age 48.9 years) and 29 otolaryngologists (42% female, mean age 37.4 years). Patients and otolaryngologists selected a median of 10 and 11 terms, respectively, to define a sinus infection. Among patients the most frequently selected symptom categories were mucus (500, 89.3%), pressure/pain (480, 85.7%), and airflow (468, 83.6%). Compared to patients, clinicians selected with greater frequency the symptom categories of pressure/pain (14.3% difference; 95% CI, 7.6% to 22.5%), mucus (10.7% difference; 95% CI, 4.7% to 18.3%) and airflow (13.0% difference; 95% CI, 4.8% to 21.7%). Multiple categories were selected by 96% of patients and 100% of providers. Conclusion: The definition of sinus infection appears variable for both patients and otolaryngologists, though patients appear to apply a broader range of symptoms to the term sinus infection. There were no pronounced geographic differences in the description of a sinus infection in this US sample population. Patients commonly described sinus infection in the context of pain‐related symptoms. Appreciation of these semantic differences may enable more effective patient‐clinician communication. [ABSTRACT FROM AUTHOR]

Premise: Plant disease severity assessments are used to quantify plant–pathogen interactions and identify disease‐resistant lines. One common method for disease assessment involves scoring tissue manually using a semi‐quantitative scale. Automating assessments would provide fast, unbiased, and quantitative measurements of root disease severity, allowing for improved consistency within and across large data sets. However, using traditional Root System Markup Language (RSML) software in the study of root responses to pathogens presents additional challenges; these include the removal of necrotic tissue during the thresholding process, which results in inaccurate image analysis. Methods: Using PlantCV, we developed a Python‐based pipeline, herein called RootDS, with two main objectives: (1) improving disease severity phenotyping and (2) generating binary images as inputs for RSML software. We tested the pipeline in common bean inoculated with Fusarium root rot. Results: Quantitative disease scores and root area generated by this pipeline had a strong correlation with manually curated values (R2 = 0.92 and 0.90, respectively) and provided a broader capture of variation than manual disease scores. Compared to traditional manual thresholding, images generated using our pipeline did not affect RSML output. Discussion: Overall, the RootDS pipeline provides greater functionality in disease score data sets and provides an alternative method for generating image sets for use in available RSML software. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to evaluate the role of the systemic immune inflammation index (SII), C‐reactive protein/albumin ratio (CAR), the monocyte/lymphocyte ratio (MLR), and the neutrophil/lymphocyte ratio (NLR) in predicting disease severity, treatment, and prognosis in multisystem inflammatory syndrome in children (MIS‐C). Methods: This medical record review retrospectively evaluated the clinical and laboratory findings of 191 MIS‐C patients followed in the Department of Pediatric Rheumatology at Ankara City Hospital, Turkey. The patients were grouped by disease severity: mild, moderate, and severe. SII, CAR, MLR, and NLR were calculated for each group. Results: All patients had fever at the time of admission; 153 (80.1%) had gastrointestinal tract involvement, 74 (38.7%) had rash, 63 (33%) had conjunctivitis, 107 (56%) had cardiac involvement, 32 (15.6%) had renal involvement, and 143 (74.9%) had hematological involvement. According to logistic regression analysis, SII, NLR, MLR, and CAR were found to be predictive indexes for disease severity, need for intensive care, need for inotropes, and anakinra treatment in MIS‐C. The cut‐off values of ≥1605.3 for SII, ≥9.1 for NLR, and ≥3.9 for CAR increased the risk of severe disease by 3.4, 7.1, and 5.7 times, respectively. Conclusion: NLR, SII, MLR, and CAR are effective and useful for predicting the severity of MIS‐C, the need for intensive care, and the need for anakinra treatment. [ABSTRACT FROM AUTHOR]

The clinical features and factors associated with disease severity in children with hemorrhagic fever with renal syndrome (HFRS) have not been well characterized. This study analyzed the clinical and laboratory factors associated with disease severity in children with HFRS caused by Hantaan virus. Data in pediatric patients with HFRS were retrospectively collected from Xi'an Children's Hospital over a 9‐year period. Independent factors associated with disease severity were identified. Nomogram predicting disease severity was constructed based on variables filtered by feature selection. In total, 206 children with HFRS were studied. Fever, digestive tract symptoms, headache, backache, bleeding, and renal injury signs were the common symptoms. Elevated white blood cell, reduced platelet, hematuria, proteinuria, coagulation abnormalities, increased blood urea nitrogen (BUN) and procalcitonin (PCT), decreased estimated glomerular filtration rate and low serum Na+, Cl−, and Ca2+ were the common laboratory findings. In the 206 patients, 21 patients had critical type disease and 4 patients (1.9%) died. Hydrothorax, hypotension and cerebral edema/cerebral herniation at hospital admission were independent clinical characteristics, and neutrophil %, prothrombin activity, PCT, BUN, and Ca2+ at hospital admission were independent laboratory factors associated with critical disease. Feature selection identified BUN, PCT and prothrombin time as independent factors related to critical disease. A nomogram integrating BUN and PCT at admission was constructed and calibration showed high accuracy for the probability prediction of critical disease. In conclusion, this study characterized the clinical and laboratory features and constructed a nomogram predicting disease severity in pediatric HFRS, providing references for disease severity evaluation in managing children HFRS. [ABSTRACT FROM AUTHOR]