Inactive Patients Research Articles

Clinical value of the expression levels of protein tyrosine phosphatase non-receptor type 22.6 mRNA in peripheral blood mononuclear cells in Crohn's disease.

ObjectiveTo explore the relationship between the expression levels of protein tyrosine phosphatase non-receptor type (PTPN) 22.6 mRNA in peripheral blood mononuclear cells (PBMCs) and the disease activity as well as clinical characteristics in Crohn’s disease (CD) patients.MethodsA total of 480 subjects were enrolled. Data were collected including baseline information, expression levels of PTPN22.6 mRNA in PBMCs for all subjects, C-reactive protein (CRP) levels in serum, clinical characteristics, and disease activity for all patients. Expression levels of PTPN22.6 mRNA in PBMCs, CRP levels in serum, clinical characteristics according to Montreal Classification [8], and Crohn’s disease activity index (CDAI) were the primary observation outcomes.ResultsThe expression levels of PTPN22.6 mRNA (P = 0.032) in PBMCs and serum CRP levels (P < 0.001) were significantly higher in active CD patients than in inactive CD patients (P = 0.032). Correlation analysis showed that there was a positive correlation between expression levels of PTPN22.6 mRNA and CDAI value (r = 0.512, P = 0.003), as well as expression levels of PTPN22.6 mRNA and CRP levels in the CD group (r = 0.456, P = 0.006). There were significantly higher expression levels of PTPN22.6 mRNA in PBMCs in patients with structuring behavior than that in patients with non-stricturing and non-penetrating (NSNP) behaviors (P = 0.018) and penetrating behaviors (P = 0.024).ConclusionsThe expression levels of PTPN22.6 mRNA can be used as an indicator to help predict CD diagnosis, disease activity, serum CRP level, and behavior type of CD disease.

Implementation of a Physical Activity Vital Sign in Primary Care: Associations Between Physical Activity, Demographic Characteristics, and Chronic Disease Burden.

Physical activity is important to prevent and manage multiple chronic medical conditions. The objective of this study was to describe the implementation of a physical activity vital sign (PAVS) in a primary care setting and examine the association between physical activity with demographic characteristics and chronic disease burden. We extracted data from the electronic medical records of patients who had visits from July 2018 through January 2020 in a primary care clinic in which PAVS was implemented as part of the intake process. Data collected included self-reported physical activity, age, sex, body mass index, race, ethnicity, and a modified Charlson Comorbidity Index score indicating chronic disease burden. We classified PAVS into 3 categories of time spent in moderate to strenuous intensity physical activity: consistently inactive (0 min/wk), inconsistently active (<150 min/wk), and consistently active (≥150 min/wk). We used χ2 tests of independence to test for association between PAVS categories and all other variables. During the study period, 13,704 visits, corresponding to 8,741 unique adult patients, had PAVS recorded. Overall, 18.1% of patients reported being consistently inactive, 48.3% inconsistently active, and 33.7% consistently active. All assessed demographic and clinical covariates were associated with PAVS classification (all P < .001). Larger percentages of consistent inactivity were reported for female, older, and underweight or obese patients. Larger percentages of consistent activity were reported for male, younger, and normal weight or overweight patients. Using PAVS as a screening tool in primary care enables physicians to understand the physical activity status of their patients and can be useful in identifying inactive patients who may benefit from physical activity counseling.

Morphological brain changes between active and inactive phases of thyroid-associated ophthalmopathy: A voxel-based morphometry study

AimTo explore the morphological brain changes among active thyroid-associated ophthalmopathy (TAO) patients, inactive TAO patients and healthy controls and to investigate the neuropathological relationship of TAO using magnetic resonance imaging (MRI) data. MethodsIn this observational case-control study, we included 35 inactive TAO patients, 37 active TAO patients and 23 healthy controls. Voxel-based morphometry (VBM) analysis was conducted to evaluate the gray matter volume (GMV) changes among groups, and the correlations between GMV alterations and clinical parameters in active and inactive TAO groups were investigated. ResultsActive TAO patients showed significantly increased GMV in the right inferior frontal gyrus, left superior frontal gyrus (SFG), orbital superior frontal gyrus, orbital middle frontal gyrus, precuneus and postcentral gyrus compared with controls and significantly increased GMV in the right middle temporal gyrus, left SFG and precuneus compared with the inactive TAO group. No significant differences were observed between the inactive TAO group and healthy controls. Notably, the receiver operating characteristic (ROC) curve analysis demonstrated altered GMV among groups and significantly (p < 0.001) differentiated active TAO from inactive TAO and healthy controls. In addition, the mean GMV in precuneus and postcentral gyrus were significantly associated with clinical parameters in active TAO. ConclusionOur findings suggested the localized GMV alterations among groups were associated with the pathophysiology of TAO and served as a potential discriminative pattern to detect clinical phases of TAO at the individual level. The altered brain morphometry may suggest a corresponding process of self-repair and remodeling of the brain structure as the disease progresses in TAO.

Editor's Choice – Effect of Physical Activity and Tobacco Use on Mortality and Morbidity in Patients with Peripheral Arterial Disease After Revascularisation: A Korean Nationwide Population Based Cohort Study

To investigate the effects of physical activity (PA) and tobacco use on adverse clinical outcomes after revascularisation for peripheral arterial disease (PAD) in the Western Pacific region, where PAD cases and tobacco use are among the highest in the world. This was a retrospective cohort study using the Korean National Health Insurance Service (NHIS) database and included patients who had received revascularisation for PAD between 2010 and 2015. They were categorised as active or inactive based on the number of days per week they engaged in PA and as current or non-tobacco users (self report). The primary outcome was all cause mortality. Secondary outcomes included major adverse outcome (a composite of all cause mortality, myocardial infarction, and stroke) and major adverse limb event (MALE, a composite of amputation and recurrent revascularisation). The relatively healthy cohort comprised 8 324 patients (mean age 64.7 years; 76.9% male) following revascularisation for PAD. Among them, 32.7% were inactive and 26.4% were tobacco users. Active patients had better outcomes than inactive patients (all cause mortality adjusted hazard ratio [adjHR] 0.766; 95% CI 0.685 - 0.855, major adverse outcome adjHR 0.795; 95% CI 0.719 - 0.878, MALE adjHR 0.858; 95% CI 0.773 - 0.953). Tobacco users had poorer outcomes than non-users (all cause mortality adjHR 1.279; 95% CI 1.124 - 1.456, major adverse outcome adjHR 1.263; 95% CI 1.124 - 1.418, MALE adjHR 1.291; 95% CI 1.143 - 1.458). Even after receiving revascularisation for PAD, a sizable proportion of patients were physically inactive and used tobacco, leading to adverse clinical outcomes such as death, cardiovascular morbidity, and amputation in Korea. These modifiable risk factors should be addressed systematically, and a comprehensive approach including supervised exercise programmes and tobacco cessation is needed in patients with PAD.

Effect of different cytokines in combination with IL-15 on the expression of activating receptors in NK cells of patients with Behçet's disease.

Behçet's disease (BD) is a systemic, autoinflammatory, chronic disorder which affects various parts of the body in genetically susceptible individuals. BD has a multi-factorial etiopathogenesis which encompasses both innate and adaptive arms of immunity. NK cells, which kill virus-infected or malign cells and provide interaction between adaptive and innate immune system, are also known to involve in the pathogenesis of autoimmune/autoinflammatory diseases including BD. NK cells function in immune responses via the signals obtained from surface-expressed activating and inhibitory receptors. In this study, we aimed to explore NK cell activation status by measuring the levels of activation marker CD69 and activating receptors NKG2D, NKp30, and NKp46 as well as proliferative and cytotoxic capacities in response to stimulation with interleukin (IL)-15-combined cytokines in BD patients. CD4+ and CD8+ T cell responses were also evaluated to compare with those of NK cells. As a result, the expression of activating receptors on NK cells was demonstrated to be varied among patients with active and inactive BD and healthy controls. The proliferation levels of NK cells were elevated in BD patients, especially in inactive phase of disease compared to healthy controls. Additionally, CD107a levels of inactive BD patients were detected to be lower in comparison with healthy controls and active BD patients. These findings suggest that BD patients in active and inactive phases display different activation status of NK cells which indicate NK cells might be associated with immune attacks and remissions during the course of BD.

Therapeutic Advances in Multiple Sclerosis.

Multiple sclerosis (MS) is an autoimmune disease affecting the central nervous system that causes significant disability and healthcare burden. The treatment of MS has evolved over the past three decades with development of new, high efficacy disease modifying therapies targeting various mechanisms including immune modulation, immune cell suppression or depletion and enhanced immune cell sequestration. Emerging therapies include CNS-penetrant Bruton's tyrosine kinase inhibitors and autologous hematopoietic stem cell transplantation as well as therapies aimed at remyelination or neuroprotection. Therapy development for progressive MS has been more challenging with limited efficacy of current approved agents for inactive disease and older patients with MS. The aim of this review is to provide a broad overview of the current therapeutic landscape for MS.

Hepatitis Virus Reactivation in Patients with Psoriasis Treated with Secukinumab in a Real-World Setting of Hepatitis B or Hepatitis C Infection.

Background and ObjectiveBiologics for psoriasis, especially anti-tumor necrosis factor-α therapies, may reactivate hepatitis B virus (HBV) or hepatitis C virus (HCV) infections, as well in inactive carriers or patients with occult infection. However, some biologics, including anti-interleukin-17 therapies such as secukinumab, seem to be less likely to cause hepatitis reactivation. This study assessed the safety of secukinumab treatment in patients with psoriasis with HBV or HBC infection.MethodsThis was a retrospective cohort study of patients with moderate-to-severe psoriasis treated with secukinumab at seven Italian centers. Patients serologically positive for one or more of the following viral hepatitis markers were included: HCV antibody (± HCV-RNA positivity) and/or hepatitis B surface antigen, and/or HBV core antibody and/or HBV surface antibody (± HBV-DNA positivity). Patients received secukinumab 300 mg subcutaneously at week 0/1/2/3/4 then every 4 weeks; prophylactic therapy before starting secukinumab was prescribed where indicated. The primary study endpoint was the reactivation of hepatitis viral infection, defined as conversion to HBV-DNA or HCV-RNA positivity, with or without elevation of transaminases.ResultsSixty patients (17 with concomitant psoriatic arthritis) were included. Thirteen subjects were hepatitis B surface antigen positive, 19 were HBV core antibody positive, and 30 were positive for the HCV antibody; however, all were HCV-RNA negative. After 53.5 ± 37.5 weeks of secukinumab therapy, hepatitis reactivation occurred in only one patient, who had a reactivation of both hepatitis B and hepatitis C. This patient had not undergone hepatitis B prophylaxis or hepatitis C treatment before secukinumab.ConclusionsThese real-world data support the safety of secukinumab in patients with positive markers of HBV or HCV infection, when administered together with dedicated prophylaxis.

Proteomic characterization of the natural history of chronic HBV infection revealed by tandem mass tag-based quantitative proteomics approach.

Currently, determining when to start antiviral therapy in patients with chronic HBV infection is a controversial issue. One crucial reason is that biomarkers for distinguishing the natural history of chronic HBV infection are unmet needs. In this study, we aimed to explore novel biomarkers and therapeutic targets for the diagnosis and treatment of chronic HBV infection by using tandem mass tag (TMT)-based quantitative proteomics approach. Here, we firstly revealed the serum proteomic characterization of the natural history of chronic HBV infection using multiplex TMT labeling coupled with liquid chromatography-mass spectrometry. Then, we verified the levels of differentially expressed proteins (DEPs) across a large number of clinical samples by enzyme-linked immunosorbent assay (ELISA). We found that DEPs over the different phases of chronic HBV infection were primarily involved in the biological process of leukocyte-mediated immunity. Patients with chronic hepatitis were characterized as having an up-regulated proteasome pathway, including upregulation of proteasome activator subunit 1 (PSME1) and proteasome subunit alpha type 7 (PSMA7) levels. In addition, immune tolerant phase patients were characterized by having the lowest ephrin-B2 (EFNB2) levels and highest heat responsive protein 12 (HRSP12) levels. Moreover, inactive HBV carrier state patients were characterized by having a down-regulated glycolysis/gluconeogenesis pathway, with especially low expression of related enzymes alpha-enolase (ENO1) and fructose-1,6-bisphosphatase 1 (FBP1). What's more, HBeAg-negative chronic hepatitis patients were characterized as having the highest interleukin 18 binding protein (IL-18BP) levels. Thus, our results provide several potential diagnostic biomarkers for distinguishing the natural history of chronic HBV infection, such as PSME1, PSMA7, EFNB2, ENO1, and IL-18BP, and also present potential therapeutic interventions for chronic hepatitis B patients, such as targeting the proteasome or glycolysis/gluconeogenesis pathways. Our findings shed new light on the development of novel diagnostic biomarkers and therapeutic targets for the diagnosis and treatment of chronic HBV infection.

Patient-Reported Sexual Function in Long-Term Survivors of Anal Cancer Treated With Definitive Intensity Modulated Radiation Therapy and Concurrent Chemotherapy

PurposePelvic chemoradiation can have a profound effect on sexual function. Few data exist describing long-term sexual function patient-reported outcomes (PROs) for patients treated with intensity modulated radiation and concurrent chemotherapy (CRT) for squamous cell carcinoma of the anus (SCCA). Methods and MaterialsWe identified 248 patients with SCCA treated with CRT from 2010 to 2018 who were alive and without recurrence. We sent a PRO survey to 148 patients who agreed to participate. The survey was comprised of the PROMIS sexual function and satisfaction questionnaire, the international index of erectile function 5-item questionnaire for men, and the female sexual function index questionnaire for women. Clinical and dosimetric data were collected for each patient. We used multiple regression models to identify factors associated with sexual function PROs. ResultsOne-hundred twelve patients (45.2% of all eligible patients, 75.7% of administered surveys) completed the survey; 90 (80.4%) were women, 107 (95.5%) were white. The median (interquartile range [IQR]) age was 61.5 (53.8-66.0) years. The median (IQR) interval since CRT was 51 (37-85) months. Twelve men (54.5%) and 52 women (57.1%) were sexually active. The median (IQR) age of sexually active patients was 58.2 (50.1-64) years compared with 64.8 (59.1-68.8) years for sexually inactive patients (P < .001). The median (IQR) female sexual function index score for sexually active women was 20.2 (13.6-25.1). The median (IQR) international index of erectile function 5-item questionnaire score was 14 (6.5-19). ConclusionsPatients treated with modern CRT for SCCA experience significant long-term sexual dysfunction as reported using validated PROs. Interventions to reduce sexual toxicities and improve patient support are needed.

Comparison of long-term results of obliterative colpocleisis and reconstructive vaginal surgery including sacrospinous ligament fixation in patients with total genital prolapse.

Treatment of total genital prolapse in elderly patients is still controversial in terms of postoperative objective and subjective results. The present study aimed to compare the long-term objective and subjective cure rates of sacrospinous ligament fixation and Le Fort operation for treatment of total genital prolapse. Patients over the age of 60 with stage 3 or 4 pelvic organ prolapse that presented to the Obstetrics and Gynaecology Clinic of the Faculty of Medicine of *** University. The study sample consisted of 17 patients that underwent Le Fort operation and 29 patients that underwent sacrospinous ligament fixation. Data on duration of operation, intraoperative complications, duration of hospital stay, and differences between preoperative and postoperative estimated blood loss, postoperative complications, and relapse in the long term were obtained. Questionnaires exploring quality of life, incontinence, and pelvic floor disorders were applied to the patients. As subjective cure rates, postoperative patient satisfaction (P = 0.001), regret rate (P = 0.038) and recommendation rate (P = 0.044), as well as postoperative questionnaire results, Pelvic Floor Impact Questionnaire and SF36 were found to be significantly better in the Le Fort group (respectively P = 0.039 and 0.042). As objective cure rates, there was no difference between the two groups in terms of postoperative cystocele, rectocele, and cystorectocele (P = 0.955) and postoperative recurrence of prolapse beyond the hymen (P: 0.893). Duration of operation and duration of hospital stay were found to be significantly shorter in the Le Fort group (respectively P = 0.032 and 0.012). Le Fort operation could be the intervention of choice in sexually inactive elderly patients with stage 3 or 4 pelvic organ prolapse.

Association between Physical Activity and the Risk of Mortality and Hospitalization in Older Korean Adults with Heart Failure.

Regular exercise improves the functional ability and quality of life of patients with heart failure (HF). However, studies on the results of intensity of exercise in the older population are scarce, especially in the Asian population. A total of 8982 older people (age 65 years) with HF were selected from the Korean National Health Insurance Service-Senior database (2005-2012). Participants were stratified according to the levels of physical activity per week as follows: (1) inactive group; (2) insufficiently active group: 1-499 metabolic equivalent task minutes (MET-min)/week; (3) active group: 500-999 MET-min/week; and (4) highly active group: 1000 MET-min/week. During a median follow-up period of 3.2 years, the incidence and risk of mortality were reduced in the insufficiently active (6.7 vs. 4.2 per 100 person-years, adjusted hazard ratio [HR], 0.82; 95% confidence interval [CI], 0.71-0.94; p 0.001), active (3.8 per 100 person-years; HR, 0.81; 95% CI, 0.70-0.95; p = 0.010), and highly active (2.4 per 100 person-years; HR, 0.52; 95% CI, 0.41-0.67; p 0.001) groups compared to inactive patients. In older Asians with HF, increased physical activity reduced the risk of all-cause mortality. The mortality-reducing benefit started at a lower physical activity compared to the World Health Organization guideline (500-999 MET-min/week), and the risk decreased with more physical activity.

Interleukin-35 promotes Breg expansion and interleukin-10 production in CD19+ B cells in patients with ankylosing spondylitis

ObjectiveIL-35 is a potent immunosuppressive and anti-inflammatory cytokine, consisting of a p35 subunit and an Epstein–Barr virus–induced gene 3 (EBI3) subunit, which suppresses CD4+ effector T cell proliferation and promotes regulatory T cell (Treg) expansion. However, the effects of IL-35 on regulatory B cells (Bregs) in ankylosing spondylitis (AS) have not been explored. The present study aimed (i) to measure serum IL-35 levels and the percentages of Bregs in the peripheral blood of patients with AS and (ii) to explore their relationships in the pathogenesis of AS.MethodsA total of 77 patients with AS (AS group), including 47 inactive AS and 30 active AS cases, and 59 healthy controls (HCs) were enrolled into this study. The serum levels of IL-35 and IL-10 were detected by ELISA, and the mRNA levels of p35 and EBI3 were measured by RT–qPCR. The percentages of CD19+CD24hiCD38hi and CD19+CD24hiCD27+ Bregs and IL-35 receptor (IL-12Rβ2, IL-27Rα and gp130), IL-10, p-STAT1, p-STAT3, and p-STAT4 in CD19+ B cells were detected by flow cytometry. The correlations between IL-35 levels and percentages of Bregs were analyzed by determining Pearson’s correlation coefficient. The effect of IL-35 on Bregs was determined by mix-culture of recombinant (r) IL-35 with peripheral blood mononuclear cells (PBMCs).ResultsThe serum IL-35 and IL-10 levels, p35 and EBI3 mRNA levels, and the percentages of CD19+CD24hiCD38hi and CD19+CD24hiCD27+ Bregs were significantly lower in AS patients than those in HCs. In addition, the percentages of CD19+CD24hiCD38hi and CD19+CD24hiCD27+ Bregs in active AS patients were significantly lower than those in inactive AS patients. The serum IL-35 levels were positively correlated with the percentages of CD19+CD24hiCD38hi and CD19+CD24hiCD27+ Bregs in AS patients. IL-12Rβ2 and IL-27Rα, but not gp130 subunit, were expressed in CD19+ B cells in AS patients. RIL-35 could effectively promote CD19+CD24hiCD38hi Breg expansion and IL-10 production. Meanwhile, rIL-35 also promoted the expression of IL-12Rβ2 and IL-27Rα and the phosphorylation of STAT1 and STAT3 in CD19+ B cells.ConclusionThese results demonstrated that reduced IL-35 production may be associated with Bregs defects in AS patients. RIL-35 induced the proliferation of CD19+CD24hiCD38hi Bregs and IL-10 production, suggesting that IL-35 may serve as a reference for further investigation to develop novel treatments for AS.Key Points• Our study investigated the effects of IL-35 on Bregs in AS patients.• We found the serum IL-35, IL-10 levels, and the percentages of CD19+CD24hiCD38hi and CD19+CD24hiCD27+Bregs were significantly lower in AS patients.• The serum IL-35 levels were positively correlated with the percentages of CD19+CD24hiCD38hi and CD19+CD24hiCD27+Bregs in AS patients.• Recombinant IL-35 could effectively promote CD19+CD24hiCD38hi Breg expansion and IL-10 production.

Vitronectin, a Novel Urinary Proteomic Biomarker, Promotes Cell Pyroptosis in Juvenile Systemic Lupus Erythematosus.

Objective Identifying new markers of juvenile systemic lupus erythematosus (JSLE) is critical event to predict patient stratification and prognosis. The aim of the present study is to analyze alteration of urinary protein expression and screen potential valuable biomarkers in juvenile systemic lupus erythematosus (JSLE). Methods The urine was collected from the patients with or without JSLE and detected by mass spectrometry to analyze proteomic changes. ELISA was used to verify the Vitronectin (VTN) changes in a new set of patients. The clinical correlation was performed to analyze between VTN and clinical pathological parameters. WB and ELISA were used to analyze VTN-mediated cell pyroptosis. Results Herein, we have identified a group of 105 differentially expressed proteins with ≥1.3-fold upregulation or ≤0.77-fold downregulation in JSLE patients. These proteins were involved in several important biological processes, including acute phase inflammatory responses, complement activation, hemostasis, and immune system regulation through Gene Ontology and functional enrichment analysis. Interestingly, urinary ephrin type-A receptor 4 (EPHA4) and VTN were significantly reduced in both inactive and active JSLE patients, and VTN treatment in THP-1 derived macrophages led to a significant increased cell pyroptosis by activation of Nod-like receptor family protein 3 (NLRP3) inflammasomes, resulting in caspase-1 activation, cleaved gasdermin D (GSDMD), and IL-18 secretion. Most importantly, the urinary VTN was also linearly correlated with clinical characteristics of JSLE, implying that VTN could be a specific diagnostic biomarker to distinguish inactive and active JSLE. Conclusion This study provided a novel role of VTN in pyroptosis in JSLE through the urinary proteomic profile for JSLE, which could be a nonintrusive monitoring strategy in clinical diagnosis.

Urinary galectin-3 binding protein (G3BP) as a biomarker for disease activity and renal pathology characteristics in lupus nephritis

ObjectiveThere is an urgent need to identify novel biomarkers of LN to reflect renal histological changes. This study aims to investigate urinary G3BP levels in LN patients and their association with renal disease activity both clinically and pathologically.MethodsThis is a cross-sectional study. A total of 119 lupus nephritis patients were recruited. Thirty patients with chronic kidney diseases (CKD) and 27 healthy volunteers were also recruited as controls. Urinary G3BP was tested by ELISA. Renal histopathology was reviewed by an experienced renal pathologist. Other clinical variables were collected through chart review.ResultsThe levels of uG3BP were significantly increased in active LN patients compared to those in inactive LN (p<0.001), CKD patients (p=0.01), and healthy controls (p<0.001). ROC analysis indicated a good discrimination ability of uG3BP to differentiate active LN from CKD patients (AUC=0.7), inactive LN (AUC=0.76), or healthy controls (AUC=0.87). uG3BP was positively correlated with SLEDAI (ρ=0.352, p<0.001), rSLEDAI (ρ=0.302, p<0.001), and SLICC RAS (ρ=0.465, p<0.001), indicating a role as a biomarker of disease activity. It also correlated with clinical parameters, including 24-h urine protein, ESR, and serum C3 levels. In patients with 24-h urine protein > 3.0 g/24h, uG3BP levels were higher in proliferative LN than in membranous LN (p=0.04). They could discriminate the two pathogenic types of LN (AUC=0.72), and they also positively correlated with AI (ρ=0.389, p=0.008) and scores of hyaline deposits (ρ=0.418, p=0.006). While in patients with 24-h urine protein ≤ 3.0 g/24h, uG3BP levels were not significantly different between proliferative and membranous LN, and there was no apparent relationship between uG3BP levels with AI or with scores of hyaline deposits, but they correlated positively with scores of cellular/fibrocellular crescents (ρ=0.328, p=0.04).ConclusionuG3BP is a non-invasive biomarker for clinically and histologically reflecting disease activity. It is associated with active histological changes and can be used as a surrogate biomarker when the renal biopsy is impractical.

Estimating Day-to-Day Circadian Rhythm in Patients with Severe Acquired Brain Injury at the Beginning of In-Hospital Rehabilitation.

Patients with severe acquired brain injury (sABI) are likely to have a disturbed circadian rhythm in the early phase of neurorehabilitation. Circadian rhythm and sleep play an important role in the rehabilitation of patients with severe acquired brain injury (sABI). Research has also pointed out the importance of investigating novel ways of assessing sleep and circadian rhythm in patients with acquired brain injury. Established methods fail to apply to the heterogeneous and fluctuant biological or behavioral signals of the patients with sABI. Accelerometry (ACC) has proven a useful measure of circadian rhythm in sABI patients. However, ACC is unavailing if patients have limited motor activity due to a low consciousness level or severe paresis. Heart rate (HR) could be a viable alternative. In this study, we aim to present a novel model for the estimation of circadian rhythm and rhythm characteristics in both motor-active and -inactive patients using ACC and HR. Furthermore, we aim to present the results of the model in patients with sABI during their first three weeks of subacute in-hospital neurorehabilitation. An explorative observational study. Continuous recordings of ACC and electrocardiography were conducted. The suggested model was applied to examine circadian rhythms. This study has proven the feasibility of a novel model for the analysis of circadian rhythm. Twenty-nine patients were included, 20 motor active and nine motor inactive. Estimates of rhythm characteristics have been presented along with estimates of circadian rhythm presence or absence for both groups. The model has been successfully applied in a population of patients with sABI. The circadian rhythm of patients undergoing in-hospital neurorehabilitation is fluctuating across time and highly variant between subjects within the first three weeks after admission to sub-acute neurorehabilitation.

Probiotics in the Treatment of Inflammatory Bowel Disease in Adulthood: A Systematic Review.

Crohn's disease (CD) and ulcerative colitis (UC) are inflammatory bowel diseases (IBD) characterized by chronic uncontrolled inflammation with an increasing prevalence in western countries. Standard medications are often associated with adverse side effects. Thus, alternative therapies such as probiotic treatment are of great interest. We aimed to review the effect of probiotics in IBD patients. A systematic search strategy was carried out in PubMed in June 2021 and 22 studies published from 1997 to 2019 were included; they analyzed the influence of probiotics in adult IBD patients both in active and inactive stage of disease. Probiotic treatment in CD patients had no effect in 6 of 7 studies. Only in one study a positive effect of an adjunctive probiotic treatment next to standard treatment in CD patients was reported. In patients with active UC, a combination of standard treatment with probiotics resulted in improvement of the disease in 5 of 9 studies. Three of 7 studies among UC patients in remission demonstrated that probiotic treatment could be as effective as standard treatment. No clear evidence was found in studies comparing probiotics to placebo in inactive UC patients with ongoing standard medication. There is no clear evidence of the benefit of probiotic treatment in CD patients. In contrast, combining standard treatment with probiotics might be an option to achieve remission in active UC patients.

Synovial signal intensity on static contrast-enhanced MRI for evaluation of disease activity in juvenile idiopathic arthritis – A look at the bright side of the knee

BackgroundKnowledge on the role of synovial signal intensity (SI) grading on static contrast-enhanced (CE) MRI of the knee for assessment of disease activity in juvenile idiopathic arthritis (JIA) is lacking. ObjectivesTo assess the value of synovial SI on static CE-MRI of the knee for evaluation of disease activity in children with JIA. Materials and methodsChildren with clinically inactive and clinically active JIA who underwent static CE-MRI of the knee were included. Synovial SI was evaluated on post-contrast T1-weighted fat-saturated images using a 0.02 cm2 region of interest drawn in the area of the synovium that contained visually the highest SI. To control for potential time-dependent post-contrast enhancement variability, a ratio between the SI of the synovium to the musculus gastrocnemius was calculated. ResultsWe included 427 JIA patients (clinically inactive JIA: 150 [35,1%]; clinically active JIA: 277 [64.9%]), 65.3% female, with a mean age of 13.3 ± 3.2 years. Mean SI synovium-to-muscle ratio was 2.1 ± 0.7 in patients with clinically inactive JIA versus 2.2 ± 0.8 in patients with clinically active JIA. Subgroup analysis showed no significant difference in SI synovium-to-muscle ratio between JIA patients with clinically inactive disease and JIA patients with clinically active disease (p-value 0.22). ConclusionsEvaluation of the brightness of the synovium on static CE-MRI of the knee for assessment of JIA disease activity should be avoided, as this might lead to incorrect clinical conclusions.

Enterogenous Microbiotic Markers in the Differential Diagnosis of Crohn's Disease and Intestinal Tuberculosis.

Crohn’s disease (CD) is a chronic intestinal disorder characterized by refractory gastrointestinal ulcerations. Intestinal tuberculosis (ITB) is one common intestinal disease in east Asia. The two diseases share similar clinical manifestations and endoscopic characteristics. Thus, it is difficult to establish a definite diagnosis of CD, CD concomitant with ITB (CD-ITB), and ITB in practice. Some enterogeneous microbiotic markers have been applied to differentiate CD and ITB, but it remains unknown how they work for the three groups of patients. The aim of our study was to explore the diagnostic values of these enterogeneous microbiotic markers (ASCA IgG, ASCA IgA, ACCA, Anti-I2 and AMCA) among CD, CD-ITB, and ITB patients. A total of 124 individuals were retrospectively enrolled in this study, namely, 103 CD patients, 10 CD-ITB patients, 9 ITB patients, and 68 healthy controls. The demographic and clinical characteristics of these patients were collected and analyzed. The values of these individual or combined enterogeneous microbiotic markers in diagnosis and classification were assessed in CD, CD-ITB, and ITB patients. ASCA IgG, ASCA IgA, and AMCA could accurately differentiate CD patients from healthy controls with an area under curve (AUC) of 0.688, 0.601, and 0.638, respectively. ASCA IgG was significantly higher in CD patients than in CD-ITB patients (P = 0.0003). The Anti-I2 antibody was appropriate for distinguishing CD-ITB from ITB patients (P = 0.039). In CD patients, ASCA IgG was higher in severe patients than in mild (P <0.0001) and inactive patients (P <0.0001), respectively. AMCA was significantly elevated in severe and moderate patients compared to inactive patients (P = 0.001, P = 0.003, respectively). AMCA was associated with a higher risk of CD-related surgery with a significant P-value of 0.0038. In our cohort, ASCAs and AMCA could accurately distinguish CD from healthy controls with an acceptable AUC. A combination of elevated ASCA IgG and AMCA antibodies established a higher sensitivity in differentiating CD from healthy controls. Elevated ASCA IgG demonstrated a differential diagnostic value between CD and CD-ITB. Anti-I2 could also distinguish CD-ITB from ITB. The level of AMCA was associated with both disease severity and CD-related surgery. Likewise, the level of ASCA IgG was also related to disease severity.

Does Preoperative Activity Level Affect Postoperative Outcomes Following Total Hip Arthroplasty?

BackgroundMany patients electing to undergo total hip arthroplasty (THA) value continuing active lifestyles when considering treatment options. Addressing these concerns requires evaluating the effect of preoperative activity level on patient-reported outcomes and improvement following THA. MethodsThree hundred thirty-five patients (368 hips) who underwent THA with a minimum 6-month (mean 533 ± 271 days) follow-up completed preoperative and postoperative University of California, Los Angeles (UCLA) activity score along with various patient-reported measures of function, pain, and mental state. Preoperative UCLA score divided patients into inactive, mild, and active groups. Analysis of covariance controlling for age, sex, body mass index, surgical approach, implant, bilateral cases, conversions, and follow-up time evaluated differences among groups for postoperative outcomes with subsequent Tukey-Kramer pairwise comparisons. ResultsMildly active patients (73:139 male:female) had better postoperative outcomes than inactive patients (40:70 male:female) for UCLA score, EuroQol Visual Analog Scale (EQVAS), Hip Outcome Score (HOS), 12-item Short-Form (SF-12) Physical, and Visual Analog Pain Scale (average/now/worst) (P values <0.001/<0.001/<0.001/<0.001/0.003/<0.001/<0.001). Active patients (32:14 male:female) had better postoperative outcomes than inactive patients for UCLA score, EQVAS, HOS, SF-12 Physical, and Visual Analog Pain Scale Worst (P values <0.001/0.024/0.001/0.001/0.017). No postoperative outcome differences existed between active and mild patients. Inactive patients displayed greater outcome improvements than mildly active patients for UCLA score, Harris Hip Score, and International Hip Outcome Tool (P values <0.001/<0.001/0.013) and active patients for UCLA score, EQVAS, HOS, International Hip Outcome Tool, and SF-12 Physical (P values <0.001/0.008/0.013/0.022/0.004). ConclusionsInactive patients achieve greater measure improvements following THA. Active patients achieve better absolute outcomes than inactive patients; however, increasing activity levels do not incrementally improve patient-reported outcome measures. Patients similarly improve pain and mental health regardless of activity level.

Vitamin D supplementation in inflammatory bowel disease: a narrative review.

Inflammatory bowel disease is a chronic disorder characterized by exacerbation and remission periods, and its worldwide incidence has increased in recent decades. Vitamin D is involved in immune regulation and improves barrier functions and intestinal microbiota. Studies have observed that high vitamin D levels decrease relapses and improve the clinical course of inflammatory bowel disease. The objective of this review was to analyze the evidence on vitamin D supplementation in adult patients with inflammatory bowel disease. Among inactive patients, the studies administrating less than 2000 international units per day of vitamin D did not find any beneficial effects. However, those supplementing 2000 international units of vitamin D per day increased serum levels and reduced disease activity. In patients with active disease, doses between 5000 to 10 000 international units per day reduced symptomatology. This review showed that vitamin D supplementation above 2000 international units per day among inactive patients with inflammatory bowel disease, and between 5000 to 10 000 international units per day among those in the active stage, shows potential benefits on the disease.