Shorter Disease Research Articles

P769 Impact of discontinuation of anti-TNF therapy: A long term follow-up data of risks and predictors relapse in a large Indian cohort

Abstract Background Discontinuation of anti-TNF therapy in IBD is an important consideration in TB endemic low resource settings of the developing world. There are no established guidelines on withdrawal of biologics. A proper exit strategy on when and how biologics can be stopped is therefore warranted. We aimed to identify risk factors and rates of relapse post withdrawal in a large real-life cohort of patients from India. Methods Prospectively collected data of consecutive patients treated with anti-TNFs from the IBD registry of a large tertiary care centre was analyzed. Demographics,baseline disease characteristics,reasons for discontinuation, response to anti-TNF,and relapse rate after withdrawal were analysed. Time to event analysis was done to evaluate relapse rates over time. Cox proportional hazard analysis and non-parametric tests were performed to identify risk factors of relapse. Results Of 8300 patients, only 725(8.7%),(Median age-36y,IQR:26-47,61.2% male,61.2%CD, 32%UC, IBD-U 1.8%) received anti-TNFs. 445 (61.3%) discontinued with median follow up of 54 m(IQR:31-81). Reasons for discontinuation were primary non-response(64,14.3%);secondary loss of response (44,9.8%);financial constraints(27,6.1%);TB reactivation (18,4%), side effects(17,3.2%); infusion reactions(20,4.4%);non-compliance(4,0.9%), and COVID lockdown (6,1.3%). Overall, 232/445 (52%) were in clinical and endoscopic remission while stopping anti-TNFs with median follow up of 41 months(IQR:24.5-67). Relapse rates at 1,2,3,4, and 5 years after discontinuation were 16%,5.6%,5.2%,2.6% and 1.3% respectively. Overall,161/232(69%) patients remained in remission(Fig1A). Patients who stopped after clinical and endoscopic remission had higher likelihood of maintaining remission after discontinuation of biologics (Log-rank test,p=0.001). On multivariate analysis, fistulizing disease(p=0.03), prior history of bowel surgery (p=0.019), immunomodulator usage (p=0.001) and shorter duration of therapy (p=0.017) were associated with significantly higher rate of relapse(Table1). Cumulative time to relapse was significantly longer in those with or without endoscopic remission (median 17.3 vs 7 months;p=0.04)(Fig1B). On the other hand, shorter disease duration (p=0.001) and absence of extra-intestinal manifestations (p=0.009) were associated with lower risks of relapse. Conclusion 60% of patients discontinued anti-TNF therapy in this real world cohort. However, long-term cumulative relapse rates were low(30%), particularly in non-fistulizing disease, with no history of bowel surgery or extra intestinal manifestations and in endoscopic remission. A definite exit strategy appears feasible and would be a practical and affordable management approach.

Time is myelin: early cortical myelin repair prevents atrophy and clinical progression in multiple sclerosis.

Cortical myelin loss and repair in multiple sclerosis (MS) have been explored in neuropathological studies, but the impact of these processes on neurodegeneration and the irreversible clinical progression of the disease remains unknown. Here, we evaluated in vivo cortical demyelination and remyelination in a large cohort of people with all clinical phenotypes of MS followed up for 5 years using magnetization transfer imaging (MTI), a technique that has been shown to be sensitive to myelin content changes in the cortex. We investigated 140 people with MS (37 clinically isolated syndrome, 71 relapsing-MS, 32 progressive-MS), who were clinically assessed at baseline and after 5 years and, along with 84 healthy controls, underwent a 3 T-MRI protocol including MTI at baseline and after 1 year. Changes in cortical volume over the radiological follow-up were computed with a Jacobian integration method. Magnetization transfer ratio was employed to calculate for each patient an index of cortical demyelination at baseline and of dynamic cortical demyelination and remyelination over the follow-up period. The three indices of cortical myelin content change were heterogeneous across patients but did not significantly differ across clinical phenotypes or treatment groups. Cortical remyelination, which tended to fail in the regions closer to CSF (-11%, P < 0.001), was extensive in half of the cohort and occurred independently of age, disease duration and clinical phenotype. Higher indices of cortical dynamic demyelination (β = 0.23, P = 0.024) and lower indices of cortical remyelination (β = -0.18, P = 0.03) were significantly associated with greater cortical atrophy after 1 year, independently of age and MS phenotype. While the extent of cortical demyelination predicted a higher probability of clinical progression after 5 years in the entire cohort [odds ratio (OR) = 1.2; P = 0.043], the impact of cortical remyelination in reducing the risk of accumulating clinical disability after 5 years was significant only in the subgroup of patients with shorter disease duration and limited extent of demyelination in cortical regions (OR = 0.86, P = 0.015, area under the curve = 0.93). In this subgroup, a 30% increase in cortical remyelination nearly halved the risk of clinical progression at 5 years, independently of clinical relapses. Overall, our results highlight the critical role of cortical myelin dynamics in the cascade of events leading to neurodegeneration and to the subsequent accumulation of irreversible disability in MS. Our findings suggest that early-stage myelin repair compensating for cortical myelin loss has the potential to prevent neuro-axonal loss and its long-term irreversible clinical consequences in people with MS.

Mortality in childhood-onset type 1 diabetes mellitus with onset between 1959 and 1996: A population-based study in Hokkaido, Japan.

To examine the mortality rate and causes of death in childhood-onset type 1 diabetes in Japan. For a median 36.7years, we followed 391 patients under the age of 15years who developed type 1 diabetes between 1959 and 1996. We calculated the mortality rate per 100,000 person-years and the standardised mortality ratio (SMR) according to risk factors. The mortality rates and SMRs were 823 and 8.8 with onset during 1959-1979, 370 and 5.9 with onset during 1980-1989, and 133 and 3.2 with onset during 1990-1996, respectively. The mortality rates and SMRs were 359 and 8.4 in men, and 235 and 6.0 in women. Mortality rates and SMRs were 452 and 7.3 in patients with diabetes onset before puberty and 514 and 6.3 in patients with onset after puberty. The main causes of death with shorter disease duration were sudden death, accident/suicide, and acute diabetic complications. With a more than 30-year disease duration, the main causes of death were end-stage renal disease and cardiovascular disease. This cohort study revealed a decrease in the mortality rate between 1959-1979 and 1990-1996 in patients with childhood-onset type 1 diabetes in Japan. Patients with onset after puberty had a higher mortality rate than those with onset before puberty.

P1149 Risk of Clostridioides difficile infection in patients with inflammatory bowel disease

Abstract Background Patients with inflammatory bowel disease (IBD) are at increased risk of Clostridioides difficile infection (CDI). CDI in IBD patients has been associated with poor clinical outcomes including higher morbidity and mortality. Immunosuppressant therapy has been proposed as a risk factor for CDI. However, the particular relationship between biologic therapy and CDI is controversial. We aimed to assess whether biologic therapy increased the risk of developing CDI in three cohorts of patients with immune-mediated inflammatory diseases (IBD and rheumatic diseases). Methods We conducted a retrospective study including three cohorts: IBD patients receiving biologic therapies (IBD-Bio), IBD patients treated with non-biologic therapies (IBD-Bio-naïve), and patients with rheumatic diseases receiving biologics (RHEUMA-Bio). Different biologic agents were considered for IBD-Bio cohort: infliximab, adalimumab, golimumab, certolizumab, ustekinumab, and vedolizumab. For RHEUMA-Bio, the biologics included were infliximab, adalimumab, golimumab, certolizumab, ustekinumab, secukinumab, etanercept, abatacept, tocilizumab, rituximab, guselkumab and ixekizumab. We estimated the incidence rate (IR) of CDI episodes between 2015 and 2021 among the three cohorts. Risk factors of CDI were assessed using logistic regression model. Furthermore, we performed subgroup analysis to identify risk factors of CDI in the IBD cohorts (IBD-Bio and IBD-Bio-naïve) and within the IBD-Bio cohort. We used R software for data analysis. Results Overall, we included 1868 patients, 603 in IBD-Bio, 440 in IBD-Bio-naïve, and 825 in the RHEUMA-Bio cohort. The number of CDI episodes was 3, 42, and 25 for the RHEUMA-Bio, IBD-Bio, and IBD-Bio-naïve cohorts, respectively. The IR for CDI was 1.27 100 person-years (95% confidence interval [95% CI], 0.91-1.71) for IBD-Bio, followed by 0.95 100 person-years (95% CI 0.61-1.40) for IBD-Bio-naïve and declined to 0.07 100 person-years (95% CI 0.01-0.20) for RHEUMA-Bio cohort. We identified having IBD (odds ratio [OR]:18.98, CI 95% 5.82- 61.92, p&amp;lt;0.001) as the major risk factor for developing CDI after adjusting for age, sex, need for biologics, and comorbidities in the three cohorts. Among IBD patients, there were no differences in CDI between biologic and naive cohorts. Within the IBD-Bio cohort, the number of biologics received (OR: 1.56, CI 95% 1.22- 2.01, P&amp;lt;0.001) and short disease duration (1.08, CI 95% 1.04- 1.13, P&amp;lt;0.001) were associated with a higher risk of CDI. Conclusion The major risk factor associated with CDI development was the diagnosis of IBD. Biologic therapy was not associated with a higher risk of CDI. In IBD patients on biologic therapy, the number of biologics received increased the risk of CDI.

P725 Predictive factors for biologic therapy initiation after ileal pouch-anal anastomosis

Abstract Background Patients with ulcerative colitis (UC) undergoing proctocolectomy and Ileal Pouch-Anal Anastomosis (IPAA) frequently develop long-term complications, such as chronic pouchitis and Crohn’s-like disease of the pouch. These may eventually require biologic therapy. We aimed to identify peri-operative predictors for biologic therapy after IPAA. Methods All patients after IPAA followed at Rabin Medical Center pouch clinic and consenting to prospective observational follow up were included. Patients undergoing IPAA due to familial adenomatous polyposis (FAP) and those with ileostomy were excluded. Primary outcome was the initiation of biologic therapy after IPAA. We used Cox proportional hazard models to evaluate the following potential predictors: gender, race, smoking status, BMI category, UC duration until surgery, surgery indication, immediate post-operative complications (bowel obstruction, infection and leakage), and pre-operative treatment with 5-ASA, steroids, immunomodulators, and biologic therapy. Results Out of 174 patients in our cohort, 18 were excluded due to FAP and 8 due to ileostomy, leaving 148 for analysis. Prior to IPAA, 52 patients (35%) were treated with biologic therapy. Median follow-up from ileostomy closure to last documented visit was 15.14 years. During this period, 32 patients (21.6%) initiated biologic therapy, including 18 with adalimumab (12.2%), 10 with infliximab (6.7%), 2 with ustekinumab (1.3%), 1 with golimumab (0.6%), and 1 with vedolizumab (0.6%). Median time-to biologic therapy initiation was 10.1 years (IQR 10.0). Significant hazard ratios (HR) for biologic therapy initiation were pre-operative treatment with biologic therapy (HR 4.8, 95% CI; 2.3-10, p&amp;lt;0.001); Arab descent (HR 4.7, 95% CI; 1.6-14, p=0.005); pre-operative treatment with immunomodulators (HR 3.0, 95% CI; 1.3-7, p=0.011); UC duration of less than 10 years before ileostomy closure (HR 2.7, 95% CI; 1.2-6.3, p=0.02); past smoking status (HR 2.6, 95% CI; 1.22-5.7, p=0.013); and immediate post-operative complications (HR 2.0, 95% CI; 1.0-4.1, p=0.05). None of the patients undergoing IPAA due to dysplasia (n=27), required biologic therapy. Conclusion Pre-operative treatment with either biologic therapy or immunomodulators, Arab descent, short disease duration prior to IPAA, past smoking status, and post-operative complications were significant predictors of biologic therapy initiation post-IPAA. Patients with these risk factors may benefit from closer post-operative follow-up and earlier initiation of biologic therapy.

Predicting glucocorticoid effectiveness in thyroid eye disease: combined value from serological lipid metabolism and an orbital MRI parameter.

The aim was to determine the combined value of serological lipid metabolism and an orbital MRI quantitative parameter in predicting the effectiveness of glucocorticoid (GC) therapy in patients with thyroid eye disease (TED). This study retrospectively enrolled 46 patients with active and moderate-to-severe TED (GC-effective group, n = 29; GC-ineffective group, n = 17). Serological lipid metabolism, the orbital MRI-based minimum signal intensity ratio of extraocular muscles (EOM-SIRmin), as well as other clinical parameters before GC therapy were collected and compared between the two groups. Multivariate logistic regression and receiver operating characteristic curve analysis were adopted to identify independent predictable variables and assess their predictive performances. Compared to the GC-ineffective group, the GC-effective group showed lower serum total cholesterol levels (P = 0.006), lower serum low-density lipoprotein cholesterol levels (P = 0.019), higher EOM-SIRmin values (P = 0.005), and shorter disease durations (P = 0.017). Serum total cholesterol and EOM-SIRmin were found to be independent predictors of GC-effective TED through multivariate analysis (odds ratios = 0.253 and 2.036 per 0.1 units, respectively) (both P < 0.05). The integration of serum total cholesterol ≤4.8 mmol/L and EOM-SIRmin ≥ 1.12 had a better predictive efficacy (area under the curve, 0.834) than EOM-SIRmin alone, with a sensitivity of 75.9% and a specificity of 82.4% (P = 0.031). Serological lipid metabolism, combined with an orbital MRI-derived parameter, was a useful marker for predicting the effectiveness of GCs in patients with active and moderate-to-severe TED.

Deep resolution of clinical, cellular and transcriptomic inflammatory markers of psoriasis over 52 weeks of interleukin-17A inhibition by secukinumab.

Secukinumab, an anti-interleukin (IL)-17A monoclonal antibody, induces histological and molecular resolution of psoriatic plaques by 12 weeks. However, the long-term effects of secukinumab on the molecular resolution of psoriatic inflammation remain unknown. To investigate the molecular resolution of psoriasis following 52 weeks of secukinumab treatment. This was a two-part phase II randomized double-blinded placebo-controlled 52-week study of patients with moderate-to-severe psoriasis receiving secukinumab 300 mg (NCT01537432). Psoriatic lesional and nonlesional skin biopsies were obtained at baseline and at weeks 12 and 52, and the composition of the residual disease genomic profile (RDGP; i.e. 'molecular scar') of biopsies from secukinumab responders analysed. After 52 weeks of treatment, 14 of 24 enrolled patients were considered to be clinical responders [≥ 75% improvement in Psoriasis Area and Severity Index (PASI 75)], 4 of 24 were considered to be nonresponders (< PASI 75) and 6 of 24 patients were lost to follow-up; both the histological and transcriptomic profiles of PASI 75 responders improved from week 12 to week 52. RDGP transcripts of histological responders only partially overlapped between weeks 12 and 52, despite a similar number of transcripts in each RDGP; specifically, four novel transcript subsets showed distinct expression dynamics between weeks 12 and 52 ('slow-resolving', 'recurring', 'persistent' and 'resolved'), with anti-inflammatory and immunomodulatory genes (e.g. SOCS1, CD207 and IL37) notably restored at week 52. Shorter disease duration prior to secukinumab treatment coincided with greater transcript improvements at weeks 12 and 52. Secukinumab improves the histological and molecular phenotype of psoriatic lesional skin up to 52 weeks of treatment; these results suggest possible mechanisms that drive long-term control of psoriasis.

Quality of life, stress, anxiety and depression and associated factors among people with type 2 diabetes mellitus in Western region Saudi Arabia.

The objective of this study is to evaluate the quality of life (QoL), depression, anxiety, and stress, along with associated factors among individuals with diabetes in Saudi Arabia. This survey was conducted at King Abdulaziz University (KAU), Jeddah, Kingdom of Saudi Arabia (KSA). The assessment of depression, anxiety, and stress related to Type 2 Diabetes Mellitus (T2DM) was conducted using the DASS-21 questionnaire, while diabetes-related QoL was evaluated using the revised version of the diabetes QoL questionnaire (RV-DQoL13). Data were analyzed using SPSS-26. A total of 251 subjects were included in the study (165 [65.7%] males and 86 [34.3%] females, mean age 50.1 ± 14.5 years). The individuals with DM had a mean value of QoL of 29.16 ± 9.23, with 46.9% having poor QoL. Furthermore, in dimensions of QoL, almost half of the individuals reported high worry about the disease (49.6%), followed by a high diabetes impact (46.6%) and low life satisfaction (42.9%). The prevalence of depression, anxiety, and stress was 49.4, 71.7, and 49.8%, respectively. A significant correlation was found between depression, anxiety, and stress and DASS-21 scores with QoL (p < 0.001). The regression analysis indicated an association of distinct factors with QoL like age above 41 years (p = 0.004), being married (p < 0.001), being divorced (p = 0.04), higher education (p = 0.007), regular medicine intake (p = 0.01), regular exercise (p = 0.03), lipid profile (p = 0.01), HbA1c (p < 0.001), and DASS-21 scores (p < 0.001). Poor QoL score (TQoL score > 27) was significantly associated with depression, anxiety, and stress (p < 0.001). The participants with higher monthly income, shorter disease duration, regular medicine use, and altered lipid profile, and older subjects had a lower chance of depression, anxiety, and stress. Approximately half of individuals with T2DM experienced poor QoL, while the prevalence rates for depression, anxiety, and stress were 49.4, 71.7, and 49.8%, respectively. Scores in the domains of impact, worry, and satisfaction were below optimal levels. Several factors were linked to QoL and depression, anxiety, and stress, and an association was observed between DASS-21 scores and QoL.

Sleep, Anxiety, Somatization, Quality of Life, and Resilience in Pediatric Patients With Eosinophilic Esophagitis.

Emerging evidence suggests a high burden of psychosocial comorbidities in patients with eosinophilic esophagitis (EoE), although factors associated with this burden have not been explored. We aimed to increase understanding of the psychosocial burden of EoE and assess factors that are associated with disease burden. We conducted a cross-sectional study of patients with EoE (n = 87) recruited from a single-center, multidisciplinary pediatric eosinophilic gastrointestinal disorders clinic (2019-2021). Participants (aged 8-18 years) completed validated assessments during routine clinic visit to assess EoE symptoms (Pediatric Eosinophilic Esophagitis Symptom Score version 2.0), quality of life (Pediatric Quality of LIfe- Eosinophilic Esophagitis), anxiety state and trait (State-Trait Anxiety Score for Children), somatization (Child Somatic Symptoms Inventory 24), sleep disordered breathing (Pediatric Sleep Questionnaire) and, in a subset (n = 35), resilience (Connor Davidson Resilience Scale). Clinical and demographic data were collected. Participants were at a mean (SD) age of 12.8 (3.1) years, and 26% (n = 23) were female. Shorter disease duration (6-12 months) was associated with higher symptom burden ( P = 0.03), somatization ( P < 0.01), and anxiety (State-Trait Anxiety Score for Children Trait P < 0.01) scores. Participants with neurodevelopmental comorbidities had higher anxiety trait, somatization, sleep disordered breathing, and lower quality of life ( P < 0.01 for all). Symptom burden was significantly associated with increased somatic symptoms (adjusted β [aβ] = 0.34; 95% confidence interval 0.23-0.45) and decreased quality of life (aβ = -0.42; 95% confidence interval -0.59 to -0.25) but not state anxiety, trait anxiety, or disordered sleep breathing. Pediatric patients with a recent diagnosis of EoE can experience higher EoE symptoms, somatization, and anxiety when compared with those with a longer-standing diagnosis. Patients earlier in their diagnosis and with neurodevelopmental disorders may experience increased somatization and anxiety that may warrant additional support services.

Shorter Crohn’s Disease Duration Is Associated With Better Clinical and Endoscopic Outcomes With Risankizumab in Phase 3 Studies

Early biologic therapy treatment has demonstrated better outcomes in Crohn's disease (CD). We evaluated the impact of CD duration in patients with moderately to severely active CD treated with risankizumab therapy. This post hoc analysis evaluated clinical, endoscopic, and safety outcomes by baseline CD duration (<2, 2-5, >5-10, and >10 years) in patients from ADVANCE, MOTIVATE, and FORTIFY. Pooled induction analyses included patients who received intravenous 600-mg dose of risankizumab or placebo for 12 weeks. Maintenance analyses included patients who responded to induction risankizumab and received subcutaneous 180-mg or 360-mg dose of risankizumab for 52 weeks. Duration subgroups were compared using Cochrane-Armitage trend tests with nominal P values. Among 527 patients who received risankizumab 600-mg induction therapy, higher outcome rates were observed at week 12 among patients with shorter vs longer baseline disease duration (for <2, 2-5, >5-10, and >10 years, clinical remission: 42.7%, 46.9%, 43.5%, and 33.2% [P= .046]; endoscopic response: 48.3%, 36.3%, 32.0%, and 33.4% [P= .025]). Among 298 patients receiving risankizumab (180 mg or 360 mg) maintenance therapy, shorter vs longer baseline disease duration was generally associated with numerically higher endoscopic outcome rates at week 52. Higher clinical remission and endoscopic outcome rates were generally observed with shorter disease duration with 180-mg risankizumab dose only. Adverse event rates were generally similar across duration subgroups. Clinical benefits of risankizumab are observed across disease duration subgroups; clinical and endoscopic outcome rates are higher with risankizumab initiation earlier in the disease course (ClinicalTrials.gov numbers: NCT03105128, NCT03104413, and NCT03105102).

Management of autoimmune temporal lobe epilepsy with GAD65 antibody: four case reports.

Glutamate decarboxylase (GAD) enzyme can be a target intracellular antigen in autoimmune focal epilepsy. GAD65 antibody is in found patients diagnosed with drug-refractory temporal lobe epilepsy (TLE). We explore the clinical features of the disease and therapeutic options. We present the cases of four TLE patients, two of them with type 1 diabetes. All of them were drug-resistant and therefore underwent presurgical evaluation, which revealed GAD65 antibody positivity. We discuss the four GAD65 antibody positive temporal lobe epilepsy patients' electroclinical data, the treatments, and their effectiveness. One of them became seizure-free after right anterior temporal lobe resection, two of them did not show significant improvement with immunmodulatory agents, and the fourth patient with the shortest duration of disease had significant improvement in seizure status and normalisation of cognitive status with IVIg therapy. Our cases show that the earlier a GAD65 antibody is detected, the greater the chance of achieving seizure freedom or improvements in both seizure and cognitive status with immunomodulatory agents. However, in some cases, surgery may also bring seizure freedom, but with a risk of cognitive deterioration.

Risk stratification for phenoconversion in patients with isolated REM sleep behavior disorder. A follow-up study from Turkey.

Isolated rapid eye movement (REM) sleep behavior disorder (iRBD) is one of the strongest prodromal markers of alpha-synucleinopathies. We aimed to investigate non-invasive clinical and quantitative predictors of phenoconversion from iRBD to parkinsonism. We prospectively followed-up a total of 45 patients (57.8% men) for eight years. Clinical assessments, Sniffin' Sticks Odor Identification Test, Farnsworth-Munsell 100 Hue Color Vision test, Beck Depression Inventory and Rome III Criteria for constipation were performed. Polysomnographic parameters, sleep spindles, electroencephalographic (EEG) spectral analysis, heart rate variability (HRV) were analyzed. Eight patients (17.8%) showed phenoconversion to parkinsonism after a mean duration of 3.2 ± 1 years. Odds ratio for predicting phenoconversion was highest for patients =60 years of age with anosmia and constipation -44.8 (4.5-445.7); kappa = 4.291-. Duration, frequency or density of sleep spindles failed to demonstrate significant correlations. In EEG spectral analysis, lower alpha power in occipital region during wakefulness and REM sleep was significantly correlated with phenoconversion. Slowing in EEG spectrum power, together with age =60 years, anosmia and constipation, resulted in the highest odds ratio -122.5 (9.7-1543.8); kappa = 3.051-. It is of great importance to have a world-wide perspective of phenoconversion rates from iRBD to overt neurodegeneration, since racial and geographical factors may play important modifying roles. Relatively younger age and shorter disease duration may also be confounding factors for lower rate in our study. Neurophysiological biomarkers seem to be important predictors of phenoconversion, though more research is needed to establish subtypes of iRBD with different probabilities of evolution to overt synucleinopathy.

Early psoriatic arthritis: when is the right time to start advanced therapy?

Despite significant advances in the treatment of psoriatic arthritis (PsA) in the last two decades, remission remains elusive and there is no cure. Evidence from rheumatoid arthritis (RA) confirming enhanced response and outcome from earlier treatment intervention suggests the plausibility of the window of opportunity in the pathogenesis of RA. Yet, data are lacking in PsA. Although treatment response may be enhanced in shorter disease duration, it is unknown how this early intervention may impact long-term outcomes. Furthermore, it remains to be demonstrated whether there is a best treatment strategy and time of intervention. Crucially, the main hurdle when aiming for early treatment intervention is the ability to achieve a timely diagnosis that highlights the need to focus research efforts on characterizing the very early disease stages including the transition to PsA in the at-risk psoriasis population.

Medication Adherence Among Hypertensive Patients in Kurdistan Region of Iraq: An Observational Follow-Up Study

Background: Adherence to medications is a main concern to hypertension control and incidence of CVD complications. This study aimed to measure the level of medication adherence of hypertensive patients after one month follow-up. Methods: An observational one-month follow-up study was conducted in 93 hypertensive patients in Kurdistan Region. Results: Patients’ mean age was 55.03 (25-85 years). The mean value of the MARS score of adherences was 7.68 out of 10. The mean values of dimensions of adherence were 3.20 of 4 (medication adherence behavior), 2.92 of 4 (attitude toward taking medication), and 1.55 of 2 (negative side effects and attitudes to medication). We found that the males, single and married, urban, those with no chronic disease, and those with higher levels of education were more likely to adhere to medication. The patients with shorter disease duration and treatment had higher adherence scores. The patients with no experience of the medication side effects had higher levels of medication adherence (8.80 vs. 7.00; P&lt;0.0001) and patients who took fewer tablets/day. Conclusions: We observed high-adherence level among hypertensive patients. Prolong disease duration, long treatment duration, increase number of tablets/days, and increase number of comorbidities may significantly decrease the medication adherence rate.

Immunosuppressive therapy and COVID-19 infection in patients with NMOSD.

To evaluate whether treated with immunosuppressants in neuromyelitis optica spectrum disorder (NMOSD) shows an effect on the severity and outcomes of COVID-19 Omicron variant. This is a substudy of a single-center clinical trial involving human umbilical cord mesenchymal stem cells (hUC-MSCs) in NMOSD patients. NMOSD patients with hUC-MSCs treatment, NMOSD patients without hUC-MSCs treatment, and matched healthy controls (HC) were included. Demographic information, NMOSD-related clinical features, comorbidities, use of disease-modifying therapy, COVID-19 vaccination status, COVID-19 clinical features, COVID-19 clinical outcomes, and NMOSD-related disease activity were obtained through online questionnaires or phone calls. The majority of NMOSD patients received long-term treatment with mycophenolate mofetil (68.8%) or azathioprine (22.9%), and 50% received oral glucocorticoid. During the epidemic, 97.4% of NMOSD patients infected with COVID-19 had asymptomatic or mild forms, with only two patients (2.6%) requiring hospitalization. None of these patients required tracheal intubation or admission to the intensive care unit. Clinical symptoms were found to be more prevalent in HC groups. Additionally, the HC groups had higher fever-recorded temperatures. NMOSD patients who received hUC-MSCs treatment had shorter disease duration than patients who did not receive hUC-MSCs treatment. Immunosuppressant-treated patients with NMOSD have a similar risk of COVID-19 infection as the general population, but the disease duration is shorter and the clinical symptoms are less severe. Among our NMOSD patients who received hUC-MSCs treatment, COVID-19 outcomes were favorable, with no increased risk of severe COVID-19. Prospective studies on immunotherapies are needed to help determine best treatment practices.

Observational study on stability of within-day glycemic variability of type 2 diabetes inpatients treated with decoctions of traditional Chinese medicine.

Within-day glycemic variability (GV), characterized by frequent and significant fluctuations in blood glucose levels, is a growing concern in hospitalized patients with type 2 diabetes mellitus (T2DM). It is associated with an increased risk of hypoglycemia and potentially higher long-term mortality rates. Robust clinical evidence is needed to determine whether traditional Chinese medicine (TCM) decoctions can be a beneficial addition to the management of within-day GV in this patient population. This retrospective cohort study utilized data from adult inpatients diagnosed with T2DM admitted to the Traditional Chinese Medicine Hospital of Kaifeng. The primary outcome investigated was the association between the use of TCM decoctions and improved stability of within-day GV. Blood glucose variability was assessed using the standard deviation of blood glucose values (SDBG). For each patient, the total number of hospitalization days with SDBG below 2mmol/L was calculated to represent within-day GV stability. Hospitalization duration served as the secondary outcome, compared between patients receiving TCM decoctions and those who did not. The primary analysis employed a multivariable logistic regression model, with propensity score matching to account for potential confounding variables. A total of 1,360 patients were included in the final analysis. The use of TCM decoctions was significantly associated with enhanced stability of within-day GV (OR = 1.77, 95% CI: 1.34-2.33, P < 0.01). This association was most prominent in patients with a diagnosis of deficiency syndrome (predominantly qi-yin deficiency, accounting for 74.8% of cases) and a disease duration of less than 5years (OR = 2.28, 95% CI: 1.21-4.29, P = 0.03). However, TCM decoctions did not exert a statistically significant effect on hospitalization duration among patients with T2DM (OR = 0.96, 95% CI: 0.91-1.01, P = 0.22). This study suggests that TCM decoctions may be effective in improving within-day GV stability in hospitalized patients with T2DM. This effect appears to be most pronounced in patients diagnosed with deficiency syndrome, particularly those with qi-yin deficiency and a shorter disease course. Further investigation is warranted to confirm these findings and elucidate the underlying mechanisms.

Immune Profiling of Patients with Systemic Sclerosis through Targeted Proteomic Analysis.

High-throughput proteomic analysis could offer new insights into the pathogenesis of systemic sclerosis (SSc) and reveal non-invasive biomarkers for diagnosis and severity. This study aimed to assess the protein signature of patients with SSc compared to that of healthy volunteers, decipher various disease endotypes using circulating proteins, and determine the diagnostic performance of significantly expressed plasma analytes. We performed targeted proteomic profiling in a cohort of fifteen patients with SSc and eighteen controls using the Olink® (Olink Bioscience, Uppsala, Sweden)Target 96 Inflammation Panels. Seventeen upregulated proteins involved in angiogenesis, innate immunity, and co-stimulatory pathways discriminated between patients with SSc and healthy controls (HCs) and further classified them into two clusters, a low-inflammatory and a high-inflammatory endotype. Younger age, shorter disease duration, and lack of reflux esophagitis characterized patients in the low-inflammatory endotype. TNF, CXCL9, TNFRSF9, and CXCL10 positively correlated with disease progression, while the four-protein panel comprising TNF, CXCL9, CXCL10, and CX3CL1 showed high diagnostic performance. Collectively, this study identified a distinct inflammatory signature in patients with SSc that reflects a persistent T helper type 1 (Th 1) immune response irrespective of disease duration, while the multi-protein panel might improve early diagnosis in SSc.

A two-component model of hair cortisol concentration in fibromyalgia: Independent effects of pain chronicity and severity.

Fibromyalgia (FM) is a chronic pain disorder of unknown aetiopathogenesis, in which the role of activity of the hypothalamic-pituitary-adrenal (HPA) axis is not clearly established. This study analysed the modulatory effects of disease chronicity and severity on cortisol levels. Hair cortisol concentrations (HCC) and clinical evaluation data (pain severity, impact of FM on daily activities, depression, anxiety, fatigue and insomnia) were collected from 47 female patients with FM and 36 healthy women (HW). The results showed that disease chronicity, with a negative effect, and symptom severity, with a positive effect, were independent predictors of HCC. Patients with a shorter disease duration had higher HCC than patients with a longer disease duration and healthy participants. Furthermore, patients with greater symptom severity had higher HCC than those patients with lower clinical severity and healthy participants. While disease chronicity in FM was associated with a decrease in HCC, clinical severity increased HCC. These results support the existence of a dysfunction in the regulation of the HPA axis in FM and its possible contribution to chronic pain development. This is the first study to assess hair cortisol concentrations in a specific sample of patients with fibromyalgia (FM). This method is especially useful for the assessment of long-term regular cortisol excretion. Results showed a two-component model for explaining cortisol levels: disease chronicity, with a negative effect, and symptom severity, with a positive effect. This suggests that severe pain/stress evokes higher cortisol levels at earlier stages of FM, while in the longer term a decrease in cortisol levels was observed.

Abnormal dopamine transporter imaging in pure autonomic failure: a potential biomarker of central nervous system involvement.

Pure autonomic failure (PAF) is a rare progressive neurodegenerative disease characterized by neurogenic orthostatic hypotension at presentation, without other neurological abnormalities. Some patients may develop other central neurological features indicative of multiple system atrophy or a Lewy body disorder. There are currently no biomarkers to assess possible central nervous system involvement in probable PAF at an early stage. A possibility is to evaluate the nigrostriatal dopaminergic degeneration by imaging of dopamine transporter with DaTscan brain imaging. The objective was to evaluate subclinical central nervous system involvement using DaTscan in PAF. We retreospectively reviewed pure autonomic failure patients who were evaluated at the Autonomic Unit between January 2015 and August 2021 and underwent comprehensive autonomic assessment, neurological examination, brain magnetic resonance imaging and DaTscan imaging. DaTscan imaging was performed if patients presented with atypical features which did not meet the criteria for Parkinson's disease or multiple system atrophy or other atypical parkinsonism. In this cohort, the median age was 49.5 years at disease onset, 57.5 years at presentation, and the median disease duration was 7.5 years. Five of 10 patients had an abnormal DaTscan without neurological features meeting the criteria of an alternative diagnosis. Patients with abnormal DaTscan were predominantly males, had shorter disease duration and had more severe genitourinary symptoms. Degeneration of nigrostriatal dopaminergic neurons measured using DaTscan imaging can present in patients with PAF without concurrent signs indicating progression to widespread α-synucleinopathy. It is advocated that DaTscan imaging should be considered as part of the workup of patients with emerging autonomic failure who are considered to have PAF.

Establishing mRNA and microRNA interactions driving disease heterogeneity in amyotrophic lateral sclerosis patient survival.

Amyotrophic lateral sclerosis is a fatal neurodegenerative disease, associated with the degeneration of both upper and lower motor neurons of the motor cortex, brainstem and spinal cord. Death in most patients results from respiratory failure within 3-4 years from symptom onset. However, due to disease heterogeneity some individuals survive only months from symptom onset while others live for several years. Identifying specific biomarkers that aid in establishing disease prognosis, particularly in terms of predicting disease progression, will help our understanding of amyotrophic lateral sclerosis pathophysiology and could be used to monitor a patient's response to drugs and therapeutic agents. Transcriptomic profiling technologies are continually evolving, enabling us to identify key gene changes in biological processes associated with disease. MicroRNAs are small non-coding RNAs typically associated with regulating gene expression, by degrading mRNA or reducing levels of gene expression. Being able to associate gene expression changes with corresponding microRNA changes would help to distinguish a more complex biomarker signature enabling us to address key challenges associated with complex diseases such as amyotrophic lateral sclerosis. The present study aimed to investigate the transcriptomic profile (mRNA and microRNA) of lymphoblastoid cell lines from amyotrophic lateral sclerosis patients to identify key signatures that are distinguishable in those patients who suffered a short disease duration (<12 months) (n = 22) compared with those that had a longer disease duration (>6 years) (n = 20). Transcriptional profiling of microRNA-mRNA interactions from lymphoblastoid cell lines in amyotrophic lateral sclerosis patients revealed differential expression of genes involved in cell cycle, DNA damage and RNA processing in patients with longer survival from disease onset compared with those with short survival. Understanding these particular microRNA-mRNA interactions and the pathways in which they are involved may help to distinguish potential therapeutic targets that could exert neuroprotective effects to prolong the life expectancy of amyotrophic lateral sclerosis patients.