Diagnostic values, association with disease activity and possible risk factors of anti-PAD4 in rheumatoid arthritis: a meta-analysis.

OBJECTIVE: Anti-peptidyl arginine deaminase 4 (anti-PAD4) antibody has been a subject of investigation in RA in the last two decades. This meta-analysis investigated the diagnostic values, association with disease activity and possible risk factors of anti-PAD4 antibody in rheumatoid arthritis. METHOD: We searched studies from five databases up to 1 December 2022. Bivariate mixed-effect models were used to pool the diagnostic accuracy indexes, and the summary receiver operating characteristics (SROC) curve was plotted. The quality of diagnostic studies was assessed using QUADAS-2. Non-diagnostic meta-analyses were conducted using the random-effects model. Sensitivity analysis, meta-regression, subgroup analyses and Deeks' funnel plot asymmetry test were used to address heterogeneity. RESULT: Finally, 24 journal articles and one letter were included. Anti-PAD4 antibody had a good diagnostic value between RA and healthy individuals, but it might be lower between RA and other rheumatic diseases. Moreover, anti-PAD4 could slightly enhance RA diagnostic sensitivity with a combination of ACPA or ACPA/RF. Anti-PAD4 antibody was positively correlated with HLA-SE and negatively correlated with ever or current smoking in patients with RA. RA patients with anti-PAD4 antibody had higher DAS28, ESR, swollen joint count (SJC) and the possibility of having interstitial lung disease (ILD) and pulmonary fibrosis compared with those without. CONCLUSION: Our study suggests that anti-PAD4 antibody is a potentially useful diagnostic biomarker and clinical indicator for RA. Further mechanistic studies are required to understand the impact of HLA-SE and smoking on the production of anti-PAD4 antibody.

Effects of age and disease duration on the efficacy and safety of iGlarLixi in Asian people with type 2 diabetes: A post hoc analysis of the LixiLan-O-AP and LixiLan-L-CN trials.

AIM: To evaluate the effect of age and disease duration on the efficacy and safety of iGlarLixi versus insulin glargine 100 units/ml (iGlar) or lixisenatide (Lixi) alone in Asian people with type 2 diabetes (T2D) uncontrolled on oral antidiabetic drugs (LixiLan-O-AP) or basal insulin ± oral antidiabetic drugs (LixiLan-L-CN). MATERIALS AND METHODS: In this post hoc analysis, the glycated haemoglobin (HbA1c) changes were assessed from baseline to week 24 (LixiLan-O-AP) or 30 (LixiLan-L-CN) in subgroups defined by baseline age (<65, ≥65 years) and duration of T2D. The proportion who achieved the composite of HbA1c <7% (<53.0 mmol/mol) without weight gain and without symptomatic hypoglycaemia (plasma glucose ≤3.9 mmol/L) and the incidences of hypoglycaemia and gastrointestinal disorders were also analysed. RESULTS: HbA1c reductions were consistently greater with iGlarLixi versus iGlar or Lixi across all subgroups, including participants aged ≥65 years and those with T2D for ≥15 or ≥20 years. Greater proportions of participants achieved HbA1c <7% (<53.0 mmol/mol) without weight gain or hypoglycaemia with iGlarLixi versus iGlar or Lixi, regardless of age or T2D duration. Hypoglycaemia incidence was similar with iGlarLixi versus iGlar across most subgroups; the incidence of gastrointestinal disorders was lower with iGlarLixi versus Lixi in all subgroups. CONCLUSIONS: iGlarLixi showed consistent efficacy and safety across all age and disease duration subgroups in Asian people with uncontrolled T2D, including older individuals and those with longstanding disease.

Living in environmental justice areas worsens asthma severity and control: Differential interactions with disease duration, age at onset, and pollution.

BACKGROUND: Impoverished and historically marginalized communities often reside in areas with increased air pollution. OBJECTIVE: We evaluated the association between environmental justice (EJ) track and asthma severity and control as modified by traffic-related air pollution (TRAP). METHODS: We performed a retrospective study of 1526 adult asthma patients in Allegheny County, Pa, enrolled in an asthma registry during 2007-20. Asthma severity and control were determined using global guidelines. EJ tract designation was based on residency in census tracts with ≥30% non-White and/or ≥20% impoverished populations. TRAP exposures (NO2 and black carbon) for each census tract were normalized into pollution quartiles. Generalized linear model analyses determined the effect of EJ tract and TRAP on asthma. RESULTS: TRAP exposure in the highest quartile range was more frequent among patients living in an EJ tract (66.4% vs 20.8%, P < .05). Living in an EJ tract increased the odds of severe asthma in later onset asthma. The odds of uncontrolled asthma increased with disease duration in all patients living in EJ tracts (P < .05). Living in the highest quartile of NO2 also increased the odds of uncontrolled asthma in patients with severe disease (P < .05), while there was no effect of TRAP on uncontrolled asthma in patients with less severe disease (P > .05). CONCLUSIONS: Living in an EJ tract increased the odds of severe and uncontrolled asthma and was influenced by age at onset, disease duration, and potentially by TRAP exposure. This study underscores the need to better understand the complex environmental interactions that affect lung health in groups that have been economically and/or socially marginalized.

Associations of disease duration and anti-citrullinated peptide antibody status with the effectiveness of abatacept in biologic-naïve patients with rheumatoid arthritis: Post hoc analysis of a multicentre, real-world observational study in Japan (ORIGAMI).

OBJECTIVES: The aim of the article is to investigate the associations of disease duration and anti-cyclic citrullinated peptide antibody (ACPA) status with the effectiveness of abatacept in biologic-naïve patients with rheumatoid arthritis (RA). METHODS: We performed post hoc analyses of the Orencia® Registry in Geographically Assembled Multicenter Investigation (ORIGAMI) study of biologic-naïve RA patients aged ≥20 years with moderate disease activity who were prescribed abatacept. Changes in the Simplified Disease Activity Index (SDAI) and Japanese Health Assessment Questionnaire (J-HAQ) at 4, 24, and 52 weeks of treatment were analysed in patients divided according to ACPA serostatus (positive/negative), disease duration (<1/≥1 year), or both. RESULTS: SDAI scores decreased from baseline in all groups. SDAI scores tended to decrease more in the ACPA-positive group and disease duration <1-year group than in the ACPA-negative group and disease duration ≥1-year group, respectively. In the disease duration <1-year group, SDAI tended to decrease more in the ACPA-positive group than in the ACPA-negative group. Disease duration was independently associated with the change in SDAI and SDAI remission at Week 52 in multivariable regression models. CONCLUSIONS: These results suggest that starting abatacept within 1 year of diagnosis was associated with greater effectiveness of abatacept in biologic-naïve patients with RA and moderate disease activity.

[Staging of COVID-19 morphological manifestations in lungs depending on disease duration]. / Stadiinost' morfologicheskikh proyavlenii COVID-19 v legkikh v zavisimosti ot davnosti zabolevaniya.

OBJECTIVE: To determine morphological alterations in lung tissues in the case of novel coronavirus infection (COVID-19) in the aspect of process staging with consideration to disease duration. MATERIAL AND METHODS: The number of COVID-19-related deaths of patients aged 55-65 years equal 17 were investigated. Serial cuts of lung tissue stained with hematoxylin and eosin, obtained from several lung fragments of each corpse, were analyzed. Morphological features previously described in literature sources were taken into account. RESULTS AND CONCLUSION: It has been established, that processes in lungs have a phasic character, furthermore they are not clearly delimited in time. In addition, there were no morphological features specific to COVID-19. Obtained results may allow forensic medical experts-histologists to predict the COVID-19 duration.

Temporal Relationship between Impairment of Cerebellar Motor Learning and Deterioration of Ataxia in Patients with Cerebellar Degeneration.

Ataxia and impaired motor learning are both fundamental features in diseases affecting the cerebellum. However, it remains unclarified whether motor learning is impaired only when ataxia clearly manifests, nor it is known whether the progression of ataxia, the speed of which often varies among patients with the same disease, can be monitored by examining motor learning. We evaluated motor learning and ataxia at intervals of several months in 40 patients with degenerative conditions [i.e., multiple system atrophy (MSA), Machado-Joseph disease (MJD)/spinocerebellar ataxia type 3 (SCA3), SCA6, and SCA31]. Motor learning was quantified as the adaptability index (AI) in the prism adaptation task and ataxia was scored using the Scale for the Assessment and Rating of Ataxia (SARA). We found that AI decreased most markedly in both MSA-C and MSA-P, moderately in MJD, and mildly in SCA6 and SCA31. Overall, the AI decrease occurred more rapidly than the SARA score increase. Interestingly, AIs remained normal in purely parkinsonian MSA-P patients (n = 4), but they dropped into the ataxia range when these patients started to show ataxia. The decrease in AI during follow-up (dAI/dt) was significant in patients with SARA scores < 10.5 compared with patients with SARA scores ≥ 10.5, indicating that AI is particularly useful for diagnosing the earlier phase of cerebellar degeneration. We conclude that AI is a useful marker for progressions of cerebellar diseases, and that evaluating the motor learning of patients can be particularly valuable for detecting cerebellar impairment, which is often masked by parkinsonisms and other signs.

Performance of serum neurofilament light chain in a wide spectrum of clinical courses of amyotrophic lateral sclerosis-a cross-sectional multicenter study.

BACKGROUND AND PURPOSE: The objective was to assess the performance of serum neurofilament light chain (sNfL) in amyotrophic lateral sclerosis (ALS) in a wide range of disease courses, in terms of progression, duration and tracheostomy invasive ventilation (TIV). METHODS: A prospective cross-sectional study at 12 ALS centers in Germany was performed. sNfL concentrations were age adjusted using sNfL Z scores expressing the number of standard deviations from the mean of a control reference database and correlated to ALS duration and ALS progression rate (ALS-PR), defined by the decline of the ALS Functional Rating Scale. RESULTS: In the total ALS cohort (n = 1378) the sNfL Z score was elevated (3.04; 2.46-3.43; 99.88th percentile). There was a strong correlation of sNfL Z score with ALS-PR (p < 0.001). In patients with long (5-10 years, n = 167) or very long ALS duration (>10 years, n = 94) the sNfL Z score was significantly lower compared to the typical ALS duration of <5 years (n = 1059) (p < 0.001). Furthermore, in patients with TIV, decreasing sNfL Z scores were found in correlation with TIV duration and ALS-PR (p = 0.002; p < 0.001). CONCLUSIONS: The finding of moderate sNfL elevation in patients with long ALS duration underlined the favorable prognosis of low sNfL. The strong correlation of sNfL Z score with ALS-PR strengthened its value as progression marker in clinical management and research. The lowering of sNfL in correlation with long TIV duration could reflect a reduction either in disease activity or in the neuroaxonal substrate of biomarker formation during the protracted course of ALS.

Neuropsychiatric Status of Patients With Multiple Sclerosis Across Disease Duration Intervals.

OBJECTIVES: The neuropsychiatric sequelae of multiple sclerosis (MS) are important predictors of morbidity and mortality. The authors examined how symptoms of depression, anxiety, fatigue, subjective cognitive impairment, and objective cognitive dysfunction varied with disease duration. They also explored changes in the use of disease-modifying therapies, psychotropic medications, and psychotherapies in relation to disease duration. METHODS: A retrospective sample of 464 people with MS was stratified into three groups based on disease duration: <5 years (N=129), 5-10 years (N=101), and >10 years (N=234). Symptoms of depression and anxiety were recorded with the Hospital Anxiety and Depression Scale (HADS); fatigue, with the five-item version of the Modified Fatigue Impact Scale (MFIS-5); subjective cognitive impairment, with the five-item version of the Perceived Deficits Questionnaire (PDQ-5); and cognition, with the Minimal Assessment of Cognitive Function in MS (MACFIMS). RESULTS: There were between-group differences in anxiety symptoms (p<0.01) and degree of cognitive impairment (p=0.03), but there were no differences in depressive symptoms, fatigue, or subjective cognitive difficulties. Anxiety was higher during the first 5 years after diagnosis, and cognitive dysfunction was higher when assessed more than 10 years after diagnosis. With longer disease duration, a greater proportion of participants received psychotropic medications (p<0.01), and lower proportions received disease-modifying therapies (p<0.01) or psychotherapies (p<0.01). CONCLUSIONS: Findings indicated that rates of some neuropsychiatric symptoms, such as anxiety and cognitive dysfunction, may shift with disease duration, whereas other symptoms, such as fatigue and depression, may not. These findings highlight the importance of closely monitoring the mental state of people with MS over time.

Analysis of 30 patients with cupulolithiasis of the posterior semicircular canal.

BACKGROUND: The diagnostic characteristics of patients with cupulolithiasis of the posterior semicircular canal are persistent torsional nystagmus in the supine position and persistent torsional nystagmus (opposite direction) in the nose-down position, which are caused by the affected canal becoming gravity sensitive. OBJECTIVE: To investigate the clinical features of posterior cupulolithiasis. MATERIALS AND METHODS: We interviewed 30 consecutive patients with cupulolithiasis of the posterior canal and categorized them by onset time into the following four groups: (1) during sleep; (2) at the time of awakening; (3) morning; and (4) afternoon. We defined disease duration as the period from onset to the day when we detected remission of positional nystagmus. RESULTS: Time of awakening was the most common onset time. The mean disease duration was 18.2 days, and 90% of patients achieved cure within 1 month. CONCLUSIONS: Physicians should take into account the duration of nystagmus, because cupulolithiasis of posterior canal exists. The etiology of posterior cupulolithiasis is closely related to sleep, because time of awakening is the most common onset time of vertigo. Most patients with posterior cupulolithiasis cure within 1 month.

PECULIARITIES OF DYNAMICS OF INDICATORS OF PROTEINS OXIDATIVE MODIFICATION AND MATRIX METALLOPROTEINASE-9 ACTIVITY IN PATIENTS WITH PARANOID SCHIZOPHRENIA DEPENDING ON THE DISEASE DURATION.

OBJECTIVE: The aim: The objective of the research was to study the indicators of oxidative modification of proteins (OMP) and the activity of matrix metalloproteinase-9 (MMP-9) in patients with paranoid schizophrenia depending on the disease duration. PATIENTS AND METHODS: Materials and methods: 320 patients were included in the examination. 20 patients were with "Primary psychotic episode" (Comparison Group) and 300 patients were diagnosed with "Paranoid schizophrenia" (Experimental Group): 60 of them have suffered from this disease for a duration from 3 to 5 years (Subgroup I ); 60 patients have suffered for a period from 6 to 10 years (Subgroup II); 60 individuals - from 11 to 15 years (Subgroup III); 60 patients have suffered for a duration from 16 to 20 years (Subgroup IV); 60 patients - from 21 years and longer (Subgroup V). RESULTS: Results: The presented data showed that the levels of OMP indicators in Subgroup I constituted 0.826±0.046 conventional units at a wavelength of 356 nm; 0.864±0.051 conventional units at a wavelength of 370 nm; 0.444±0.019 conventional units at a wavelength of 430 nm; 0.176±0.007 conventional units at a wavelength of 530 nm, which is 1.99; 1.6; 1.13 and 1.43 times higher than in the Comparison Group. The content of OMP products was higher by 2.24; 1.74; 1.17, and 1.43 times in Subgroup II, respectively, by 2.4; 1.80; 1.36 and 1.46 times in Subgroup III, respectively; by 2.5; 1.9; 1.4; 1.6 times in Subgroup IV, respectively; by 2.5; 2.02; 1.54; 1.7 times in Subgroup V, respectively. The conducted correlation analysis indicated a direct correlation between OMP indicators and the disease duration. The concentration of MMP-9 in the patients of the Comparison Group was equal to 892.84±87.80 pg/ml, which was 11.2% less compared to the Experimental Subgroup I, where this indicator was 992.84±67.50 pg/ml. MMP-9 constituted 1092.53±47.20 pg/ml on average in the patients of Subgroup II, which was 22.36% higher than in the Comparison Group. This indicator was 1702.84±37.60 pg/ml in Subgroup III, which was 90.7% higher than in the Comparison Group. It constituted 1492.84±47.29 pg/ml in Subgroup IV, which was 67.2% higher than in the Comparison Group; and 2037.21±57.80 pg/ ml in Subgroup V, which was more than two times higher than in the Comparison Group (p<0.05). The conducted correlation analysis showed a direct relation between MMP-9 expression and the increase in OMP indicators. This relation was more significant between MMP-9 and OMP products of a neutral nature. The correlation strength between MMP-9 and OMP products of a basic nature was somewhat less significant. CONCLUSION: Conclusions: According to the results of the conducted analysis, the examined patients had the signs of decompensation of reactive-adaptive biomolecular mechanisms which activated radical reactions with the subsequent accumulation of oxidation products.

Effect of disease duration on fecal biomarkers in ulcerative colitis: a prospective cohort study.

BACKGROUND: Biomarkers such as fecal calprotectin (FC) and fecal immunochemical occult blood tests (FIT) for ulcerative colitis (UC) are used in clinical practice. In this study, the effect of UC disease duration on FC was investigated and compared to that on FIT. METHODS: One hundred twenty-eight colonoscopic examinations and two fecal biomarkers measurements were performed. The cases of UC were divided into short- and long-term disease-duration groups or categorized into three groups with disease durations of 0-5, 6-13, and 14-38 years. We analyzed correlations between biomarker levels and endoscopic scores, including the Mayo endoscopic subscore (MES), ulcerative colitis endoscopic index of severity, and the sum of MES. RESULTS: In the analysis of short- and long-term disease durations, the three endoscopic scores and biomarker levels showed significant correlations in both long-term and short-term groups. Most of the correlation coefficients for the individual long-term group were lower than the corresponding values for all cases, while most of the correlation coefficients for the individual short-term groups were higher than the corresponding values for all cases. In the three-group analysis (disease durations of 0-5, 6-13, and 14-38 years), the two biomarkers and three endoscopic scores showed significant correlations, and most of the correlation coefficients between biomarkers and endoscopic scores tended to be lower in the long-term follow-up group. In the receiver operating characteristic analysis for predicting mucosal healing in the three groups, the area under the curve for FC and FIT concentrations in the 0-5 year disease-duration group showed particularly higher values than those for the other two groups. CONCLUSIONS: Similar to FIT, FC is affected by the duration of UC, indicating that FC may be a highly useful biomarker, especially in short-term disease.

Distal esophageal wall thickness correlates with dysphagia in adult patients with eosinophilic esophagitis.

BACKGROUND: Thickening of the esophageal wall in patients with eosinophilic esophagitis (EoE) and gastro-esophageal reflux disease (GERD) has been shown in studies using endoscopic ultrasound (EUS). We hypothesise that transmural inflammation in EoE results in prominent esophageal wall thickening compared with the mucosal inflammation in GERD. The aim of this study was to compare the relationship among dysphagia, endoscopic appearance, wall thickness, histology, and motility in EoE and GORD. METHODS: EoE and GERD patients were prospectively studied between February 2012 and April 2021. Patients were studied on 2 separate occasions with endoscopy, EUS and mucosal biopsies, followed by high-resolution manometry. Epidemiology and dysphagia data were obtained. RESULTS: A total of 45 patients (31 EoE, 14 GERD) were included. There were no significant differences in age, sex, duration of disease and presence of esophageal motility disorders. EoE patients had a higher dysphagia score (P < 0.001), EREFS score (P < 0.001) and peak eosinophil count (P < 0.001) compared with GERD patients. Thickness of the submucosa in the distal esophagus in EoE was significantly higher than GERD (P = 0.003) and positively correlated with duration of disease (P = 0.01, R = 0.67). Positive correlation was also found between dysphagia score and distal total esophageal wall thickness (P = 0.03, R = 0.39) in EoE patients. No correlation was found between these variables in GERD patients. CONCLUSION: Distal esophageal wall thickness positively correlates with dysphagia score in EoE but not GERD. This appears to be related to the composition of the submucosa which can be identified using EUS.

Effects of canagliflozin compared with placebo on major adverse cardiovascular and kidney events in patient groups with different baseline levels of HbA1c, disease duration and treatment intensity: results from the CANVAS Program.

AIMS/HYPOTHESIS: Type 2 diabetes mellitus can manifest over a broad clinical range, although there is no clear consensus on the categorisation of disease complexity. We assessed the effects of canagliflozin, compared with placebo, on cardiovascular and kidney outcomes in the CANagliflozin cardioVascular Assessment Study (CANVAS) Program over a range of type 2 diabetes mellitus complexity, defined separately by baseline intensity of treatment, duration of diabetes and glycaemic control. METHODS: We performed a post hoc analysis of the effects of canagliflozin on major adverse cardiovascular events (MACE) according to baseline glucose-lowering treatments (0 or 1, 2 or 3+ non-insulin glucose-lowering treatments, or insulin-based treatment), duration of diabetes (<10, 10 to 16, >16 years) and HbA1c (≤53.0 mmol/mol [<7.0%], >53.0 to 58.5 mmol/mol [>7.0% to 7.5%], >58.5 to 63.9 mmol/mol [>7.5 to 8.0%], >63.9 to 69.4 mmol/mol [8.0% to 8.5%], >69.4 to 74.9 mmol/mol [>8.5 to 9.0%] or >74.9 mmol/mol [>9.0%]). We analysed additional secondary endpoints for cardiovascular and kidney outcomes, including a combined kidney outcome of sustained 40% decline in eGFR, end-stage kidney disease or death due to kidney disease. We used Cox regression analyses and compared the constancy of HRs across subgroups by fitting an interaction term (p value for significance <0.05). RESULTS: At study initiation, 5095 (50%) CANVAS Program participants were treated with insulin, 2100 (21%) had an HbA1c > 74.9 mmol/mol (9.0%) and the median duration of diabetes was 12.6 years (interquartile interval 8.0-18 years). Canagliflozin reduced MACE (HR 0.86 [95% CI 0.75, 0.97]) with no evidence that the benefit differed between subgroups defined by the number of glucose-lowering treatments, the duration of diabetes or baseline HbA1c (all p-heterogeneity >0.17). Canagliflozin reduced MACE in participants receiving insulin with no evidence that the benefit differed from other participants in the trial (HR 0.85 [95% CI 0.72, 1.00]). Similar results were observed for other cardiovascular outcomes and for the combined kidney outcome (HR for combined kidney outcome 0.60 [95% CI 0.47, 0.77]), with all p-heterogeneity >0.37. CONCLUSIONS/INTERPRETATION: In people with type 2 diabetes mellitus at high cardiovascular risk, there was no evidence that cardiovascular and renal protection with canagliflozin differed across subgroups defined by baseline treatment intensity, duration of diabetes or HbA1c.

Early-stage predictors of the acute phase duration in uncomplicated COVID-19 pneumonia.

OBJECTIVE: In this study, we aimed to highlight the common early-stage clinical and laboratory variables independently related to the acute phase duration in patients with uncomplicated coronavirus disease (COVID-19) pneumonia. METHODS: In hospitalized patients, the acute phase disease duration was followed using the Brescia-COVID respiratory severity scale. Noninvasive ventilation was administered based on clinical judgment. Patients requiring oropharyngeal intubation were excluded from the study. For parameters to be measured at the hospital entrance, age, clinical history, National Early Warning Score 2 (a multiparametric score system), partial pressure of oxygen in arterial blood/fraction of inspired oxygen (P/F ratio), C-reactive protein, and blood cell count were selected. RESULTS: In 64 patients, age (direct relationship), P/F, and platelet number (inverse relationship) independently accounted for 43% of the acute phase duration of the disease (P < .001). CONCLUSIONS: For the first time, the present results revealed that the acute phase duration of noncomplicated pneumonia, resulting from severe acute respiratory syndrome coronavirus 2, is independently predicted from a patient's age, as well as based on the hospital entrance values of P/F ratio and peripheral blood platelet count.

Cerebrospinal fluid protein in Guillain-Barré syndrome: Need for age-dependent interpretation.

BACKGROUND AND PURPOSE: Elevated cerebrospinal fluid (CSF) total protein in patients with acute ascending paresis is indicative of Guillain-Barré syndrome (GBS). Recent studies showed that the outdated, but still widely used upper reference limit (URL) for CSF total protein of 0.45 g/L leads to false-positive results, mainly as a result of lack of age-adjustment. The objective of this study was to assess the frequency of increased CSF total protein in adult GBS patients according to a new age-dependent URL. METHODS: Patients with GBS treated at the Medical University of Innsbruck between 2000 and 2018 were included in this study. Demographic, clinical, electrophysiological and CSF data were obtained from patients' medical charts. Frequency of increased CSF total protein depending on disease duration was compared using the conventional URL of 0.45 g/L and the age-dependent URL. RESULTS: Ninety-seven patients with GBS aged 57 ± 18 years, comprising 38% women, underwent CSF sampling within a median of 6 days after symptom onset. The median CSF total protein concentration was 0.65 g/L and correlated with disease duration. Overall, 74% of patients had elevated CSF total protein levels using the conventional URL, as opposed to 52% applying the age-dependent URL. At 0-3, 4-7, 8-14 and >14 days after disease onset, elevated CSF total protein was found in 46%, 84%, 78% and 100% of patients using the conventional URL, and in 32%, 53%, 65% and 64% of patients using the age-dependent URL. In multivariate analysis, significant predictors of elevated CSF total protein were disease duration and the demyelinating GBS variant. Similar results were obtained for CSF/serum albumin quotient (Qalb ). CONCLUSION: Fewer true-positives for CSF total protein and Qalb must be considered in suspected GBS, especially in the early disease course.

Mood in Parkinson's disease: From early- to late-stage disease.

BACKGROUND: Although depression is known to be frequent in Parkinson's disease (PD), it is unclear how mood can change and/or impact on patient's quality of life (QoL) over time. Our aim was to analyze the frequency of depression, mood related factors and the contribution of mood to a patient's QoL perception in regard to disease duration. METHODS: PD patients recruited from the COPPADIS cohort from January 2016 to November 2017 were included in this cross-sectional study. Three groups were defined: <5 years (Group A); from 5 to <10 years (Group B); ≥10 years (Group C). Analysis with well-planned linear regression models was conducted to determine how different factors contribute to mood (Beck Depression Inventory-II [BDI-II] as dependent variable), to health-related QoL (39-item Parkinson's Disease Questionnaire [PDQ-39SI] as dependent variable) and to global QoL (European Health Interview Survey - Quality of Life Eight-Item Index [EUROHIS-QOL8] as dependent variable). RESULTS: Six hundred and sixty-three PD patients (62.6 ± 8.9 years old, 59.6% males) were included: Group A, 50.1% (n = 332); Group B, 33.3% (n = 221) and Group C, 16.6% (n = 110). There were no differences between the three groups in terms of the frequency of depressive symptoms nor the frequency of depression type (major vs. minor vs. subthreshold) (p = 0.729). However, the unique percent variance of PDQ-39SI and EUROHIS-QOL8 explained by BDI-II total score was 2 (23.7%) and threefold (26.9%), respectively, in Group C compared to the other two groups. EUROHIS-QOL8 total score provided the highest unique contribution to mood (16.8%). CONCLUSIONS: Although depression-type frequency does not appear to change over time in PD; the contribution of mood on QoL perception is greater in patients with longer disease duration.

Compared with the monocyte to high-density lipoprotein ratio (MHR) and the neutrophil to lymphocyte ratio (NLR), the neutrophil to high-density lipoprotein ratio (NHR) is more valuable for assessing the inflammatory process in Parkinson's disease.

BACKGROUND: The inflammatory response plays essential roles in the pathological process and prognosis of Parkinson's disease (PD). This research investigated the predictive value of the neutrophil to high-density lipoprotein ratio (NHR), neutrophil to lymphocyte ratio (NLR), and monocyte to high-density lipoprotein ratio (MHR) for PD. METHODS: Patients with PD (n = 98) were divided into three groups according to disease duration: < 6 years (n = 55), 6-10 years (n = 29) and > 10 years (n = 14). Based on the classification system of Hoehn and Yahr, grades 1 ~ 2.5 were considered early-stage PD (n = 44), and grades 3 ~ 5 were considered advanced-stage PD (n = 54). In addition, healthy subjects (n = 98) matched to the above PD patients in the same period were selected as the control group. Differences in the NHR, NLR, MHR and other indicators among the groups were evaluated. RESULTS: Smoking, drinking, the neutrophil count and the NHR and NLR were remarkably greater and hypertension, index of body mass, the lymphocyte count, and the levels of cholesterol in total, triglycerides, lipoprotein cholesterol with low density and uric acid were sharply lower in the PD group compared with in the control group. Analysis of multifactor logistic regression indicated that the NHR (odds ratio (adjusted OR) = 1.576, 95% CI: 1.053 ~ 2.358, P = 0.027) and NLR (adjusted OR = 1.734, 95% CI: 1.046 ~ 2.876, P = 0.033) were factors of risk for PD, while the MHR was not significantly correlated with PD. The areas under the receiver operating characteristic (ROC) curve (AUCs) for the prediction of PD by the NHR and NLR were 0.654 (95% CI: 0.583 ~ 0.721, P = 0.0001) and 0.69 (95% CI: 0.62 ~ 0.754, P < 0.0001), respectively, and the optimal cutoff values were 1.848 × 109/mmol and 2.62 × 109/mmol. Spearman's correlation analysis indicated that the NHR was correlated with the disease duration significantly negatively and that the MHR was positively correlated with disease severity. CONCLUSIONS: In summary, the NHR not only has strong predictive value for PD but is also closely related to disease duration. The NHR may be a better prediction for the long-period clinical results in PD patients than the MHR and NLR. TRIAL REGISTRATION: Clinical medical reserach center project of Qinghai Province (2017-SF-L1).

Altered DNA methylation profiles in blood from patients with sporadic Creutzfeldt-Jakob disease.

Prion diseases are fatal and transmissible neurodegenerative disorders caused by the misfolding and aggregation of prion protein. Although recent studies have implicated epigenetic variation in common neurodegenerative disorders, no study has yet explored their role in human prion diseases. Here we profiled genome-wide blood DNA methylation in the most common human prion disease, sporadic Creutzfeldt-Jakob disease (sCJD). Our case-control study (n = 219), when accounting for differences in cell type composition between individuals, identified 38 probes at genome-wide significance (p < 1.24 × 10-7). Nine of these sites were taken forward in a replication study, performed in an independent case-control (n = 186) cohort using pyrosequencing. Sites in or close to FKBP5, AIM2 (2 probes), UHRF1, KCNAB2 successfully replicated. The blood-based DNA methylation signal was tissue- and disease-specific, in that the replicated probe signals were unchanged in case-control studies using sCJD frontal-cortex (n = 84), blood samples from patients with Alzheimer's disease, and from inherited and acquired prion diseases. Machine learning algorithms using blood DNA methylation array profiles accurately distinguished sCJD patients and controls. Finally, we identified sites whose methylation levels associated with prolonged survival in sCJD patients. Altogether, this study has identified a peripheral DNA methylation signature of sCJD with a variety of potential biomarker applications.

Impact of preoperative duration of ulcerative colitis on long-term outcomes of restorative proctocolectomy.

BACKGROUND: It is unknown if ulcerative colitis (UC) duration has an impact on outcomes of ileal pouch anal anastomosis (IPAA). The aim of the study was to compare the long-term IPAA outcomes based on preoperative UC duration. METHODS: All patients with pathologically confirmed UC who underwent IPAA were included from a prospectively maintained pouch database (1983-2017).Patient's cohort was stratified according to UC duration:< 5 years,5-10 years,10-20 years,> 20 years. UC duration was defined as time interval from date of preoperative diagnosis to colectomy date. The main outcome was Kaplan-Meier pouch survival. Secondary outcomes were pouch function and quality of life. RESULTS: Out of 4502 IPAAs (1983-2016), 2797 patients were included. Treated with biologics versus 12% with UC duration > 20 years were 41% patients with UC duration < 5 years. Treated with steroids compared to shortest (34%,p < 0.001) were 54% patients with the longest disease. A total of 65% of patients with shortest disease had IPAAs performed mostly in 3 stages. Anastomotic separation and pelvic sepsis were more prevalent among shortest compared to longest disease groups. Rates of pouch-targeted fistulas, anastomotic strictures, and pouchitis were highest in longest disease group. Pouch survival was similar between groups. Multivariate analysis did not show a significant association between UC duration and pouch failure [1.05(0.97-1.1), p = 0.23].Longer UC duration was associated with increased odds of pouchitis [1.2(1.1, 1.3), p < 0.001]. Biologics agents were shown to be protective against pouchitis. CONCLUSIONS: Preoperative UC duration does not increase pouch failure risk. Longer preoperative UC duration increases the pouchitis risk. Biologic agents and three-staged IPAA are protective against pouchitis and septic complications in long-term among patients with UC.

Effect of ulcerative colitis duration on the usefulness of immunochemical fecal occult blood test result as a disease activity biomarker.

PURPOSE: The effects of ulcerative colitis (UC) duration on biomarker accuracy are unknown. We investigated the effects of UC duration on the predictive accuracy of biomarkers including immunochemical fecal occult blood test (FOBT, also known as FIT), prostaglandin E-major urinary metabolite (PGE-MUM), and C-reactive protein (CRP). METHODS: We divided 133 samples into groups based on disease duration. Clinical and endoscopic remission was defined as Lichtiger's clinical activity index (CAI) of ≤ 4, Mayo endoscopic subscore (MES) of 0, and UC endoscopic index of severity (UCEIS) of ≤ 1. RESULTS: FIT results were significantly correlated with all activity scores when the disease duration was < 4 years. When the disease duration was ≥ 4 years, FIT results were significantly correlated with the CAI and MES but not with UCEIS. When the disease duration was ≥ 5 years, FIT and CAI were significantly correlated, whereas FIT and MES or FIT and UCEIS did not show any correlation. When the duration was ≥ 4 years, PGE-MUM and CRP showed a significant correlation with CAI, MES, and UCEIS. Receiver operating characteristic curve analysis of biomarker data for predicting endoscopic remission showed that the accuracy of FIT was superior to that of PGE-MUM and CRP in the < 4-year group. CONCLUSIONS: FIT is an accurate biomarker reflecting the endoscopic score until 4 years in patients with UC. However, owing to the increased number of false negatives, the usefulness of FIT may decline after 4 years. Hence, evaluation of UC in combination with other biomarkers is recommended.