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Background: Diabetic peripheral neuropathy (DPN) in children and adolescents with type 1 diabetes mellitus (T1DM) is a growing issue, with controversial data in the terms of prevalence and evaluation timelines. Currently, there are no clear standards for its early detection. Therefore, our aim was to assess the contribution of the Michigan neuropathy screening instrument (MNSI), lipid profile, serum neuron specific enolase (NSE), and serum heat shock protein 27 (HSP 27) to the prediction of DPN in children and adolescents with T1DM. Methods: In this case-control study, fifty children diagnosed with T1DM for at least five years were enrolled and evaluated through complete neurological examination, MNSI, and nerve conduction study (NCS). Additionally, HbA1c, lipid profile, serum NSE, and serum HSP 27 levels were measured for patients and controls. Results: The prevalence of DPN in our study was 24% by NCS, and electrophysiological changes showed a statistically significant lower conduction velocity for the posterior tibial and sural nerves, as well as a prolonged latency period for the common peroneal and sural nerves in neuropathic patients. In these patients, older age, earlier age of diabetes onset, longer disease duration, higher total cholesterol, triglycerides, low density lipoprotein cholesterol, HbA1c, serum NSE, and HSP27 levels were observed. The MNSI examination score ≥ 1.5 cutoff point had an area under the curve (AUC) of 0.955, with 75% sensitivity and 94.74% specificity, according to receiver operating characteristic curve analysis. However, the questionnaire's cutoff point of ≥ 5 had an AUC of 0.720, 75% sensitivity, and 63% specificity, with improved overall instrument performance when combining both scores. Regarding blood biomarkers, serum NSE had greater sensitivity and specificity in discriminating neuropathic patients than HSP27 (92% and 74% versus 75% and 71%, respectively). Regression analysis revealed a substantial dependency for MNSI and serum NSE in predicting DPN in patients. Conclusions: Despite limited research in pediatrics, MNSI and serum NSE are promising predictive tools for DPN in children and adolescents with T1DM, even when they are asymptomatic. Poor glycemic control and lipid profile changes may play a critical role in the development of DPN in these patients, despite conflicting results in various studies. [ABSTRACT FROM AUTHOR]

Anti-IgLON5 disease is a unique condition that bridges autoimmunity and neurodegeneration. Since its initial description 10 years ago, an increasing number of autopsies has led to the observation of a broader spectrum of neuropathologies underlying a particular constellation of clinical symptoms. In this study, we describe the neuropathological findings in 22 patients with anti-IgLON5 disease from 9 different European centers. In 15 patients (68%), we observed a hypothalamic and brainstem-predominant tauopathy of varying severity in which the original research neuropathological criteria were readily applicable. This pathology was observed in younger patients (median age at onset 61 years) with a long disease duration (median 9 years). In contrast, in 7 (32%) patients, the originally described brainstem tauopathy was nearly absent or only minimal in the form of delicate threads, despite mild-to-moderate neurodegenerative features, consistent clinical symptoms and the presence of anti-IgLON5 antibodies in CSF and serum. These patients were older at onset (median 79 years) and had shorter disease duration (median < 1 year). Overall, about one-third of the patients showed concomitant TDP-43 pathology within the regions affected by tau pathology and/or neurodegeneration. Based on these observations and in view of the spectrum of the tau burden in the core regions involved in the disease, we propose a simple staging system: stage 1 mild neurodegeneration without overt or only minimal tau pathology, stage 2 moderate neurodegeneration and mild/ moderate tauopathy and stage 3 prominent neurodegeneration and tau pathology. This staging intends to reflect a potential (age- and time-dependent) progression of tau pathology, supporting the current notion that tau accumulation is a secondary phenomenon related to the presence of anti-IgLON5 antibodies in the CNS. Finally, we adapt the original research criteria of the anti-IgLON5 disease-related tauopathy to include the spectrum of pathologies observed in this larger postmortem series. [ABSTRACT FROM AUTHOR]

BackgroundObjectiveMethodResultsConclusionAssessing hand function is essential for many people with rheumatoid arthritis (RA). The Measure of Activity Performance of the Hand (MAP-Hand) allows a rapid evaluation of the hand.To translate the MAP-Hand into Turkish and investigate its psychometric properties.The MAP-Hand was translated into Turkish by using established translation guidelines. The questionnaire was pilot tested in 30 people with RA. Then, 185 adults with RA (150 women) participated in the study. Physical characteristics (age, sex, body mass index), socio-demographic information (education, employment, marital status), disease-related characteristics (RA medications, disease activity, duration of disease), hand strength (grip and pinch strengths), and patient reported outcome measures regarding pain, hand/upper extremity function, and general health status were collected. The Turkish MAP-Hand was re-administered to 109 participants in the following week.The Turkish MAP-Hand was acceptable and feasible to administer, and showed excellent internal consistency (Cronbach’s α = 0.952, confidence interval, CI = 0.942 to 0.962, p < .001). The unidimensionality of the Turkish MAP-Hand was confirmed by Rasch Analysis. Test–retest reliability was excellent (Intraclass Correlation Coefficient = 0.908, CI = 0.868 to 0.936, p < .001). The Turkish MAP-Hand showed moderate negative correlations with hand strength (Pearson’s r between −0.511 and −0.572, p < .05), and fair to excellent positive correlations with disease activity, pain, hand/upper extremity function, and general health status (Pearson’s r between 0.437 and 0.915, p < .05).The Turkish Map-Hand demonstrated adequate psychometric properties (internal consistency, structural validity, test–retest reliability, convergent validity) supporting the utility of its use for evaluating the activity performance of the hand in people with RA. [ABSTRACT FROM AUTHOR]

Background: Systemic lupus erythematosus (SLE) is a chronic inflammatory multisystemic disease. Monitoring disease activity thoughtout the disease course is important for effective management and assessment of disease outcome. Objective: To assess whether the pan-immune inflammation value (PIIV) at diagnosis could predict organ involvement and disease activity in childhood SLE (cSLE) patients after 12 months of disease onst. Methods: This is an observational retrospective multicenter study that comprised cSLE patients seen and followed at the participating centers between January 2010 and December 2022. All patients met the EULAR/ACR-19 criteria, were immunosuppressive drug-naïve at the time of SLE diagnosis and had a minimal follow-up period of 12 months. The data included clinical and laboratory findings and disease activity using the SLEDAI-2K. Receiver operating characteristic (ROC) curves were employed to determine the optimal cut-off value of PIIV and assess its predictive potential for disease activity, and organ involvement. Results: A total of 125 patients (104 female) with a median age of 16.0 (IQR 5.6) years, a median age at disease onset of 10.9 (IQR 3.0) years, and a median disease duration of 4.8 (IQR 5.3) years were included. The most frequent involved organs at diagnosis were hematological (89.6%), musculoskeletal (68.8%), mucocutaneous (63.2%), and renal (58.4%). However, at a 12-month follow-up visit, the most frequent involved organs were renal (40.0%), hematological (39.2%), musculoskeletal (15.2%), and mucocutaneous (10.4%). The median PIIV at diagnosis was 139 (IQR 229.6), while the median SLEDAI was 12 (IQR 6.5) and 3.5 (IQR 7.0) at diagnosis and 12 months, respectively. An optimal PIIV cut-off of 250 was found to be a predicative for disease activity, with a sensitivity of 45% and a specificity of 86%. The study revealed that the PIIV successfully predicted four systems in our cohort of patients. Conclusion: Our work suggests the PIIV might be a reasonable predictor for organ involvement and disease activity in newly diagnosed cSLE, though further research, particularly larger studies, is required to validate these findings, especially regarding organ involvement. [ABSTRACT FROM AUTHOR]

Background: Resting-state functional magnetic resonance imaging (rs-fMRI) reveals diverse neural activity patterns in cervical spondylosis (CS) patients. However, the reported results are inconsistent. Therefore, our objective was to conduct a meta-analysis to synthesize the findings from existing rs-fMRI studies and identify consistent patterns of neural brain activity alterations in patients with CS. Materials and methods: A systematic search was conducted across PubMed, Web of Knowledge, Embase, Google Scholar, and CNKI for rs-fMRI studies that compared CS patients with healthy controls (HCs), up to January 28, 2024. Significant cluster coordinates were extracted for comprehensive analysis. Results: We included 16 studies involving 554 CS patients and 488 HCs. CS patients demonstrated decreased brain function in the right superior temporal gyrus and left postcentral gyrus, and increased function in the left superior frontal gyrus. Jackknife sensitivity analysis validated the robustness of these findings, and Egger’s test confirmed the absence of significant publication bias (p > 0.05). Meta-regression showed no significant impact of age or disease duration differences on the results. Conclusion: This meta-analysis confirms consistent alterations in specific brain regions in CS patients, highlighting the potential of rs-fMRI to refine diagnostic and therapeutic strategies. [ABSTRACT FROM AUTHOR]

In neuroinflammation, distinguishing microglia from macrophages and identifying microglial-specific biomarkers in peripheral blood pose significant challenges. This study comprehensively profiled the extracellular vesicles (EVs) of microglia and macrophages, respectively, revealing co-expressed EVs with UCHL1 and CX3CR1 as EVs derived specifically from microglia in human blood. After extensive validation, using optimized nano flow cytometry, we evaluated plasma CX3CR1+/UCHL1+ EVs across clinical cohorts [multiple sclerosis (MS), HTLV-1 associated myelopathy (HAM), Alzheimer's disease (AD), and Parkinson's disease (PD)], along with established neurodegenerative markers (NMDAR2A and NFL). The findings discovered a notable rise in CX3CR1+/UCHL1+ EVs in MS, particularly heightened in HAM, in contrast to controls. Conversely, AD and PD exhibited unaltered or diminished levels of microglial EVs. An integrated model of CX3CR1+/UCHL1+, NMDAR2A+, and NFL+ EVs demonstrated promising diagnostic potential for distinguishing MS from controls and HAM. As to the disease duration, CX3CR1+/UCHL1+ EVs increased in the initial five years of MS, stabilizing thereafter, whereas NMDAR2A+ and NFL+ EVs remained stable initially but increased significantly in the subsequent five years, suggesting their correlation with disease duration. This study uncovers unique blood microglial EVs with potential as biomarkers for MS diagnosis, differentiation from HAM, and correlation with disease duration. [ABSTRACT FROM AUTHOR]

Objective Methods Results Interpretation Pathological studies suggest that multiple sclerosis (MS) lesions endure multiple waves of damage and repair; however, the dynamics and characteristics of these processes are poorly understood in patients living with MS.We studied 128 MS patients (75 relapsing–remitting, 53 progressive) and 72 healthy controls who underwent advanced magnetic resonance imaging and clinical examination at baseline and 2 years later. Magnetization transfer saturation and multi‐shell diffusion imaging were used to quantify longitudinal changes in myelin and axon volumes within MS lesions. Lesions were grouped into 4 classes (repair, damage, mixed repair damage, and stable). The frequency of each class was correlated to clinical measures, demographic characteristics, and levels of serum neurofilament light chain (sNfL).Stable lesions were the most frequent (n = 2,276; 44%), followed by lesions with patterns of “repair” (n = 1,352; 26.2%) and damage (n = 1,214; 23.5%). The frequency of “repair” lesion was negatively associated with disability (β = −0.04; p < 0.001) and sNfL (β = −0.16; p < 0.001) at follow‐up. The frequency of the “damage” class was higher in progressive than relapsing–remitting patients (p < 0.05) and was related to disability (baseline: β = −0.078; follow‐up: β = −0.076; p < 0.001) and age (baseline: β = −0.078; p < 0.001). Stable lesions were more frequent in relapsing–remitting than in progressive patients (p < 0.05), and in younger patients versus older (β = −0.07; p < 0.001) at baseline. Further, “mixed” lesions were most frequent in older patients (β = 0.004; p < 0.001) at baseline.These findings show that repair and damage processes within MS lesions occur across the entire disease spectrum and that their frequency correlates with patients disability, age, disease duration, and extent of neuroaxonal damage. ANN NEUROL 2024 [ABSTRACT FROM AUTHOR]

Background: Gender differences in the access to advanced therapies for Parkinson's disease (PD) are poorly investigated. Objective: The objective of this study was to investigate the presence of any gender disparity in the access to advanced therapies for PD. Design: Retrospective study. Methods: Data from patients with consistent access to the Parkinson's and Movement Disorder Center of L'Aquila over the last 10-year period were screened. Patients selected for advanced therapies were included. Results: Out of 1,252 patients, 200 (mean age ± SD 71.02 ± 9.70; 72% males; median Hoen Yahr level: 3, minimum 1 maximum 5) were selected for advanced therapies: 133 for Magnetic Resonance guided Focused Ultrasound (MRgFUS) thalamotomy (mean age ± SD 70.0 ± 8.9; 77% males), 49 for Levodopa/Carbidopa Intestinal Gel (LCIG) infusion (mean age ± SD 74.3 ± 11.4; 59% males), 12 for Deep Brain Stimulation (DBS) (mean age ± SD 71.2 ± 6.3; 75% males), and 7 for Continuous Subcutaneous Apomorphine Infusion (CSAI) (mean age ± SD 69.7 ± 5.5; 43% males). No sex differences were found in relation to age (MRgFUS group: males vs. females 70.2 ± 8.9 vs. 70.8 ± 8.9, p-value = 0.809; LCIG group: males vs. females 73.5 ± 13.0 vs. 75.5 ± 8.5, p-value = 0.557; DBS group: males vs. females 77.2 ± 8.1 vs. 67.3 ± 8.6, p-value = 0.843; CSAI group: males vs. females 73.3 ± 4.0 vs. 67.0 ± 5.2, p-value = 0.144) and disease duration (MRgFUS group: males vs. females 8.3 ± 4.4 vs. 9.6 ± 6.7, p-value = 0.419; LCIG group: males vs. females 14.5 ± 5.81 vs. 17.3 ± 5.5; p-value = 0.205; DBS group: males vs. females 15.0 ± 9.6 vs. 15.5 ± 7.7, p-value = 0.796; CSAI group: males vs. females 11.7 ± 3.7 vs. 10.3 ± 3.7, p-value = 0.505). Conclusion: The predominance of males is higher than that expected based on the higher prevalence of PD in men. Women are less confident in selecting advanced therapies during the natural progression of their disease. Factors accounting for this discrepancy deserve further investigation. [ABSTRACT FROM AUTHOR]

Background: Peripheral immunity and neuroinflammation interact with each other and they play important roles in the pathophysiology of idiopathic Parkinson's disease (IPD). There have been very few real-world reports on the relationship between peripheral immune inflammation and motor phenotypes of IPD. This study aimed to investigate the potential correlation between peripheral inflammatory indicators and motor subtypes in patients with IPD. Methods: This observational, prospective case-control study examined patients with IPD and healthy controls (HC) matched for age and sex between September 2021 and July 2023 at the Affiliated Huaian No. 1 People's Hospital of Nanjing Medical University. The levels of peripheral inflammatory indicators were collected from each patient with IPD and HCs. Differences in the levels of peripheral inflammatory indicators among groups were compared. Binary logistic regression analysis was used to explore the inflammatory mechanism underlying the motor subtype of IPD. Results: A total number of 94 patients with IPD were recruited at the Affiliated Huaian No. 1 People's Hospital of Nanjing Medical University between September 2021 and July 2023, including 49 males and 45 females, and 37 healthy volunteers matched for age and sex were also enrolled as the control group. Of the 94 patients with IPD, 42.6% performed as the TD motor subtype and 57.4% performed as the AR motor subtype. NLR and the plasma levels of IL-1βand TNF-α in the IPD group were higher than those in the HC group (P < 0.05). The disease duration, Hoehn and Yahr (H-Y) stage, NLR, and the levels of IL-1β in the AR group were higher than those in the TD group (P < 0.05). Additionally, IL-1β plasma levels and NLR were positively correlated with disease duration, H-Y stage, movement disorder society-Unified Parkinson's Disease Rating Scale-III motor score, and AR subtype. The binary logistic regression model revealed that the plasma level of IL-1β was mildly associated with the AR motor subtype and NLR was strongly associated with the AR motor subtype. The combination of NLR and IL-1β showed better performance in identifying the AR motor subtype. Conclusion: NLR is strongly associated with the AR motor subtype in IPD, and peripheral immunity is probably involved in the pathogenesis of AR motor subtype in IPD. [ABSTRACT FROM AUTHOR]

Background Objective Methods Results Conclusion Long‐term data on the effectiveness and safety of omalizumab for chronic inducible urticaria (CIndU) in large populations are lacking.To evaluate the effectiveness, safety, estimated omalizumab treatment duration and its predictors, as well as differences between CIndU subtypes, in a large long‐term CIndU cohort.A multinational multicenter study was conducted at 14 specialized urticaria centres (UCAREs), including all CIndU patients ever treated with omalizumab from 2009 until July 2022. Kaplan–Meier survival and regression analyses were performed.Across 234 CIndU patients (55% female; mean age 37 years), 76% (n = 178) had standalone CIndU and 24% (n = 56) had predominant CIndU plus minor CSU, with an observation period up to 13 years. Most CIndU patients (73%, n = 145/200 with available data on response) had complete/good response to omalizumab treatment, without significant differences between CIndU subtypes. Sixty‐two (26%) patients discontinued omalizumab; due to well‐controlled disease (47%, n = 29), ineffectiveness (34%, n = 21), side effects (3%, n = 2), combination of ineffectiveness and side effects (3%, n = 2) and other reasons (13%, n = 8). The median estimated omalizumab treatment duration exceeded 5 years (54% drug survival at 5 years) and was mostly determined by well‐controlled disease. Higher age predicted a lower chance to discontinue omalizumab due to well‐controlled disease (HR 0.969, 95%CI 0.945–0.995). CIndU subtype and presence of minor CSU were not related to response and time until omalizumab discontinuation for any reason.Omalizumab is highly effective and safe in CIndU patients, with long estimated treatment duration mainly reflecting long disease duration. Our data show omalizumab's high potential as treatment in any subtype of CIndU and support its clinical use for these patients. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the effectiveness and safety of tofacitinib in patients with ulcerative colitis (UC) in clinical practice in Lebanon. Design: This was a retrospective cross-sectional study. The data were collected from hospital records. Patients with moderate to severe UC treated with tofacitinib between 2018 and 2021 were included. Patients' demographics, disease-specific characteristics, clinical assessment at three time points (8, 26, and 52 weeks), endoscopic evaluation at 24 weeks, and adverse events were collected. Results: A total of 60 UC patients with a mean duration of disease of 7.9 ± 4.7 years were enrolled. 61.7% of patients had extensive disease, and 58.3% had received ≥ 1 biologic prior to tofacitinib. Clinical remission was reported in 25, 34, and 31 patients (41.7%, 56.7%, and 56.4%) at 8, 26, and 52 weeks respectively. Endoscopic remission (endoscopic Mayo score 0 or 1) was observed in 58.3% of patients at 52 weeks. About one-third of patients (31.7%) stopped tofacitinib at one year, primarily for lack of efficacy or loss of response, with no significant difference between biologics-naïve and experienced patients (24% vs. 37.1% respectively). No serious adverse events or deaths were reported. Adverse events were reported in 3 patients (5.0%) - one C. difficile infection, one case of reversible lymphopenia, and one case of facial acne. No serious adverse events or deaths were noted. On multivariate analysis, biologic-naïve status and reduction or normalization of CRP were associated with clinical remission (OR = 10.87, 95% CI = 1.57, 100, and OR = 78.47, 95% CI = 2.09, 2940.32 respectively), while reduction or normalization of CRP was associated with endoscopic remission at 1 year (OR = 19.03, 95% CI = 1.64, 221.09). Conclusion: Tofacitinib was effective in the treatment of moderately severe ulcerative colitis in this real-world cohort in Lebanon. Further, the predictors associated with clinical and endoscopic remissions were found to be biologic-naïve status and reduction in CRP. Observed AEs were consistent with the known safety profile. One of the major limitations of this study is the smaller sample size and the retrospective nature of the study. Key Message: What is already known on this topic: – Although effectiveness of tofacitinib in ulcerative colitis has been established via real world evidence studies (RWDs), there have been no reports of RWD in West Asia or the Middle East and North Africa (MENA) region. What this study adds: – It was observed that biologic-naïve status of patients and reduction in C-reactive protein (CRP) levels were associated with clinical and endoscopic remission outcomes. Tofacitinib was effective in the treatment of moderately severe UC in the Lebanese real-world cohort and observed AEs were consistent with the known safety profile. How this study might affect research, practice, or policy: – This study provides insights to the physicians managing UC patients in the MENA region on the expected clinical journey for patients being treated with tofacitinib as well as the predictors of outcome. Future comparisons of this study with similar RWE studies in different geographical locations, will delineate the differences, if any, in the clinical course, based on demographical factors. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic has underscored the necessity of implementing non-pharmaceutical interventions such as lockdowns to mitigate the spread of infectious diseases. This study aims to model the impact of lockdown measures on the progression of an epidemic. Using a combination of compartmental models, specifically a novel delay model, we analyze the effects of varying lockdown intensities and durations on disease transmission dynamics. The results highlight that timely and stringent lockdowns can significantly reduce the peak number of infections and delay the epidemic's peak, thereby alleviating pressure on healthcare systems. Moreover, our models demonstrate the importance of appropriate lifting of lockdowns to prevent a resurgence of cases. Analytical and numerical results reveal critical thresholds for lockdown efficacy from the epidemiological point of view, which depend on such factors as the basic reproduction number ( ℜ 0 ), disease duration, and immunity waning. In the case of a single outbreak with permanent immunity, we analytically determine the optimal proportion of isolated people which minimizes the total number of infected. While in the case of temporary immunity, numerical simulations show that the infectious cases decrease with respect to the proportion of isolated people during lockdowns; as we increase the proportion of isolated people, we have to increase the duration of lockdowns to obtain periodic outbreaks. Further, we assess the influence of epidemic with or without lockdown on the economy and evaluate its economical efficacy by means of the level of population wealth. The percentage of productive individuals among isolated people influences the wealth state of the population during lockdowns. The latter increases with the rise of the former for fixed epidemic parameters. This research provides valuable insights for policymakers in designing effective lockdown strategies to control future epidemics. [ABSTRACT FROM AUTHOR]

Introduction: Psoriasis is a chronic immune-mediated skin disease with several comorbidities and a considerable influence on quality of life. Many patients with moderate-to-severe psoriasis are undertreated and have a substantial disease duration before effective treatment is started. This study analyzed patient and disease characteristics and time to effective treatment of patients with psoriasis who consulted PsoPlus. It also examined whether a treat-to-target (T2T) approach, which is implemented in PsoPlus, has an impact on treatment choice and disease progression. Methods: Through a single center, retrospective study, 170 patients in the PsoPlus dedicated clinic were compared at moment of enrollment in PsoPlus and at the last recorded consultation in 2021. Results: Median disease duration at the first PsoPlus consultation was 16.0 (interquartile range (IQR) 19.0) years. There was a significant difference in Psoriasis Area and Severity Index (PASI) and Dermatology Life Quality Index (DLQI) between the first and the last recorded PsoPlus consultation (PASI 6.0 (IQR 6.4) vs. 0.6 (IQR 2.6); DLQI 11 (IQR 11) vs. 2 (IQR 6); p < 0.001). A weak positive Spearman correlation (rs) was found between disease duration and PASI at the first PsoPlus consultation (rs = 0.175; p = 0.034), while a weak negative correlation (rs = − 0.2; p = 0.013) was found at the last registered PsoPlus consultation. Patients with a disease duration of more than 20 years had significantly more switches of treatment than those with a shorter disease duration (p < 0.001). Median time from psoriasis onset until PASI ≤ 2 was 16.0 years. Median time from the first PsoPlus consultation until PASI ≤ 2 was 7.0 months. Conclusion: The PsoPlus program with its T2T approach effectively improves clinical outcomes and quality of life for patients with psoriasis in a relatively short period, emphasizing the value of a structured, personalized treatment plan for long-term management. [ABSTRACT FROM AUTHOR]

Temporal lobe epilepsy (TLE) frequently involves an intricate, extensive epileptic frontal‐temporal network. This study aimed to investigate the interactions between temporal and frontal regions and the dynamic patterns of the frontal‐temporal network in TLE patients with different disease durations. The magnetoencephalography data of 36 postoperative seizure‐free patients with long‐term follow‐up of at least 1 year, and 21 age‐ and sex‐matched healthy subjects were included in this study. Patients were initially divided into LONG‐TERM (n = 18, DURATION >10 years) and SHORT‐TERM (n = 18, DURATION ≤10 years) groups based on 10‐year disease duration. For reliability, supplementary analyses were conducted with alternative cutoffs, creating three groups: 0 < DURATION ≤7 years (n = 11), 7 < DURATION ≤14 years (n = 11), and DURATION >14 years (n = 14). This study examined the intraregional phase‐amplitude coupling (PAC) between theta phase and alpha amplitude across the whole brain. The interregional directed phase transfer entropy (dPTE) between frontal and temporal regions in the alpha and theta bands, and the interregional cross‐frequency directionality (CFD) between temporal and frontal regions from the theta phase to the alpha amplitude were further computed and compared among groups. Partial correlation analysis was conducted to investigate correlations between intraregional PAC, interregional dPTE connectivity, interregional CFD, and disease duration. Whole‐brain intraregional PAC analyses revealed enhanced theta phase‐alpha amplitude coupling within the ipsilateral temporal and frontal regions in TLE patients, and the ipsilateral temporal PAC was positively correlated with disease duration (r = 0.38, p <.05). Interregional dPTE analyses demonstrated a gradual increase in frontal‐to‐temporal connectivity within the alpha band, while the direction of theta‐band connectivity reversed from frontal‐to‐temporal to temporal‐to‐frontal as the disease duration increased. Interregional CFD analyses revealed that the inhibitory effect of frontal regions on temporal regions gradually increased with prolonged disease duration (r = −0.36, p <.05). This study clarified the intrinsic reciprocal connectivity between temporal and frontal regions with TLE duration. We propose a dynamically reorganized triple‐stage network that transitions from balanced networks to constrained networks and further develops into imbalanced networks as the disease duration increases. [ABSTRACT FROM AUTHOR]

The aim of the study is to expound the effect of psoriasis on salivary glands by evaluating the secretion of saliva and salivary cytokine biomarkers in patients with psoriasis. This study was conducted by recruiting 120 subjects that included 60 patients diagnosed clinically with active psoriasis and 60 healthy controls who were age and gender matched to psoriatic subjects. Unstimulated whole saliva was collected from all the subjects by spitting method, and levels of tumor necrosis factor‐alpha (TNF‐α), interferon‐gamma (IFN‐γ), interleukin‐2 (IL‐2), and IL‐10 (IL‐10) were determined via enzyme‐linked immunosorbent assay (BT Lab, Shanghai, China). Secretion of saliva in psoriasis patients was considerably reduced than in healthy controls. The concentrations of pro‐inflammatory cytokines (TNF‐α, IFN‐γ, and IL‐2) were significantly increased, whereas level of anti‐inflammatory cytokine (IL‐10) was markedly decreased in the saliva of psoriasis patients with hyposalivation compared to healthy subjects. Our results demonstrated significant negative correlation of salivary flow rates with the disease severity. No significant correlations were obtained between salivary levels of tested cytokines and salivary flow rates in our study. Findings of the study reflect inflammation of salivary glands with reduced salivary flow rates in psoriasis patients. The inflammatory responses in salivary gland tissues by virtue of increased pro‐inflammatory cytokines concentrations together with lower anti‐inflammatory cytokine levels may have a role in affecting the saliva secretion in psoriasis patients. Secretion of unstimulated saliva in psoriasis patients decreases with the severity and duration of the disease. [ABSTRACT FROM AUTHOR]

Objective: The current cross-sectional study determines the prevalence and associated factors of microalbuminuria in a focused population in Eastern India. Methods: The study was conducted in Kolkata from June to December 2022 among type 2 diabetes mellitus (T2DM) patients. Patients with T2DM aged more than 18 were included in the study, and those with overt albuminuria (>300 mg/day), congestive cardiac failure, urinary tract infection, pregnancy, human immunodeficiency virus, hepatitis B, or hepatitis C infection were excluded. Results: Among 297 T2DM patients, 130 (43.8%) had high albumin creatinine ratio (> 30 mg/g). Diabetic patients with elevated blood pressure (BP > 130/80 mm Hg) were 1.68 times (95% CI, 1.12-2.53) at risk of developing microalbuminuria. Similarly, patients with a diabetes duration of 5 years or more were 1.48 (95% CI 1.09-2.02) times more likely to develop microalbuminuria. Logistic regression also concluded that elevated blood pressure (BP > 130/80 mm Hg, P = .027) and duration of diabetes (>5 years, P = .016) were predictive of microalbuminuria. Conclusion: The current study observes a high prevalence of microalbuminuria among diabetes patients. This indicates the need for the implementation of preventive strategies for diabetic nephropathy, especially among patients with long-standing diabetes and elevated blood pressure. [ABSTRACT FROM AUTHOR]

Purpose: To assess the choroidal status of Systemic Lupus Erythematosus (SLE) patients using Optical Coherence Tomography (OCT) and OCT-Angiography. Methods: SLE patients with disease duration < 10 years, no disease activity and no ocular involvement were recruited and cross-sectionally evaluated. A demographically similar cohort of healthy subjects was used for comparison. The main outcome is choroidal vascularity index (CVI). As secondary outcomes, choriocapillaris parameters and choroidal thickness (CT) were evaluated. Results: Forty eyes of 40 subjects (20 SLE patients and 20 healthy subjects) were studied with a mean ± SD age of 36.7 ± 9.9 years. In the SLE group, the mean ± SD duration of disease was 7.35 ± 2.21 years. Increased CVI was found in the SLE group (p = 0.022). Considering the choriocapillaris, SLE patients presented a lower number (p = 0.037) and a smaller total area (p = 0.041) of signal voids. No differences between groups were found in CT. For SLE patients, CT at subfoveal, temporal and inferior locations presented a negative moderate correlation with disease duration. A strong correlation between choriocapillaris parameters and age was demonstrated for both groups. Conclusions: This study provides evidence of subclinical choroidal changes in adult SLE patients with inactive disease and no overt ocular manifestation. Increased CVI and fewer and smaller flow voids in choriocapillaris with normal CT suggest increased choroidal vascularity in SLE. [ABSTRACT FROM AUTHOR]

Objectives To assess self-reported symptoms of neuropathy, disability, pain, health-related quality of life (HR-QOL) and autonomic dysfunction in patients with vasculitis. Methods Patients with vasculitis (with or without neuropathy) were invited by Vasculitis UK to complete an anonymous online survey. Results Three hundred and twelve patients (71% female) responded. Median age was 61–70 years. Median duration of vasculitis was 4 years (<2 months to >15 years). Vasculitic types included granulomatosis with polyangiitis (34%), unspecified ANCA-associated vasculitis (13%), microscopic polyangiitis (11%), eosinophilic granulomatosis with polyangiitis (11%), giant cell arteritis (10%), non-systemic vasculitic neuropathy (2%) and other (19%). Many patients reported foot/hand symptoms suggestive of neuropathy, including numbness (64%), pain (54%) or weakness (40%). Two hundred and forty-two patients (78%) met our definition of probable vasculitic neuropathy: diagnosis of neuropathy by vasculitis team OR numbness OR weakness in feet/hands. Only 52% had been formally diagnosed with neuropathy. Compared with 70 patients without neuropathy, neuropathy patients had greater disability measured by the inflammatory Rasch-built Overall Disability Scale (centile mean 63.1 [ s. d. 17.3] vs 75.2 [16.7]; P  < 0.0001), Inflammatory Neuropathy Cause and Treatment scale (median 2 [interquartile range 1–4] vs 0.5 [0–2]; P  < 0.0001) and modified Rankin scale (median 2 [interquartile range 1–3] vs 2 [1–2)]; P  = 0.0002); greater pain on an 11-point rating scale (mean 4.6 [ s. d. 2.6] vs 3.5 [2.8]; P  = 0.0009); and poorer HR-QOL on the EQ5D-3L (summary index mean 0.58 [ s. d. 0.29] vs 0.69 [0.28]; P  < 0.0001). Two-thirds reported autonomic symptoms (not associated with neuropathy). Conclusion Neuropathy is common and associated with significant disability, pain and impaired HR-QOL in patients with systemic vasculitis. [ABSTRACT FROM AUTHOR]

Objectives Cardiovascular disease through accelerated atherosclerosis is a leading cause of mortality for patients with systemic lupus erythematosus (SLE), likely due to increased chronic inflammation and cardiometabolic defects over age. We investigated age-associated changes in metabolomic profiles of SLE patients and healthy controls (HCs). Methods Serum NMR metabolomic profiles from female SLE patients (n  = 164, age = 14–76) and HCs (n  = 123, age = 13–72) were assessed across age by linear regression and by age group between patients/HCs (Group 1, age ≤ 25, n  = 62/46; Group 2, age = 26–49, n  = 50/46; Group 3, age ≥ 50, n  = 52/31) using multiple t tests. The impact of inflammation, disease activity and treatments were assessed, and UK Biobank disease-wide association analysis of metabolites was performed. Results Age-specific metabolomic profiles were identified in SLE patients vs HCs, including reduced amino acids (Group 1), increased very-low-density lipoproteins (Group 2), and increased low-density lipoproteins (Group 3). Twenty-five metabolites were significantly altered in all SLE age groups, dominated by decreased atheroprotective high-density lipoprotein (HDL) subsets, HDL-bound apolipoprotein (Apo)A1 and increased glycoprotein acetyls (GlycA). Furthermore, ApoA1 and GlycA were differentially associated with disease activity and serological measures, as well as atherosclerosis incidence and myocardial infarction mortality risk through disease-wide association. Separately, glycolysis pathway metabolites (acetone/citrate/creatinine/glycerol/lactate/pyruvate) uniquely increased with age in SLE, significantly influenced by prednisolone (increased pyruvate/lactate) and hydroxychloroquine (decreased citrate/creatinine) treatment and associated with type 1 and type 2 diabetes by disease-wide association. Conclusions Increasing HDL (ApoA1) levels through therapeutic/nutritional intervention, whilst maintaining low disease activity, in SLE patients from a young age could improve cardiometabolic disease outcomes. Biomarkers from the glycolytic pathway could indicate adverse metabolic effects of current therapies. [ABSTRACT FROM AUTHOR]

Background: This study aimed at (1) delivering generalizable estimates of the prevalence of frontotemporal-spectrum disorders (FTSDs) in non-demented ALS patients and (2) exploring their motor-functional correlates. Methods: N = 808 ALS patients without FTD were assessed for motor-functional outcomes—i.e., disease duration, severity (ALSFRS-R), progression rate (ΔFS), and stage (King's and Milano–Torino—MiToS—systems)—cognition—via the cognitive section of the Edinburgh Cognitive and Behavioural ALS Screen (ECAS)—and behaviour—via the ECAS-Carer Interview. Neuropsychological phenotypes were retrieved via Strong's revised criteria—i.e., ALS cognitively and behaviourally normal (ALScbn) or cognitively and/or behaviourally impaired (ALSci/bi/cbi). Results: Defective ECAS-Total performances were detected in ~ 29% of patients, with the ECAS-Executive being failed by the highest number of patients (~ 30%), followed by the ECAS-Language, -Fluency, and -Memory (~ 15–17%) and -Visuospatial (~ %8). Apathy was the most frequent behavioural change (~ 28%), followed by loss of sympathy/empathy (~ 13%); remaining symptoms were reported in < 4% of patients. The distribution of Strong's classifications was as follows: ALScbn: 46.7%; ALSci/bi/cbi: 22.9%/20.0%/10.4%. Multinomial regressions on Strong's classifications revealed that lower ALSFRS-R scores were associated with a higher probability of ALSbi and ALScbi classifications (p ≤.008). Higher King's and MiToS stages were associated with a higher probability of ALSbi classification (p ≤.031). Conclusions: FTSDs affect ~ 50% of non-demented ALS patients, with cognitive deficits being as frequent as behavioural changes. A higher degree of motor-functional involvement is associated with worse behavioural outcomes—with this link being weaker for cognitive deficits. [ABSTRACT FROM AUTHOR]

'Active' and 'non-active' secondary progressive MS (SPMS) have distinct pathophysiological mechanisms and clinical characteristics, but there is still no consensus regarding the frequency of these MS forms in the real-world setting. We aimed to evaluate the frequency of 'active' and 'non-active' SPMS in a large cohort of Italian MS patients and the differences in terms of clinical and MRI characteristics and disease progression. This multicenter study collected data about MS patients who have transitioned to the SP form in the period between 1st January 2014 and 31st December 2019 and followed by the MS centers contributing to the Italian MS Registry. Patients were divided into 'active SPMS' and 'non-active SPMS', based on both reported MRI data and relapse activity in the year before conversion to SPMS. Out of 68,621, 8,316 (12.1%) patients were diagnosed with SPMS. Out of them, 872 (10.5%) were classified into patients with either 'active' or 'non-active' SPMS. A total of 237 were classified into patients with 'active SPMS' (27.2%) and 635 as 'non-active SPMS' (72.8%). 'Non-active SPMS' patients were older, with a longer disease duration compared to those with 'active SPMS'. The percentages of patients showing progression independent of relapse activity (PIRA) at 24 months were similar between 'active' and 'non-active' SPMS patients (67 [27.4%] vs 188 [29.6%]; p = 0.60). In the 'active' group, 36 (15.2%) patients showed relapse-associated worsening (RAW). Comparison of the survival curves to EDSS 6 and 7 according to disease activity did not show significant differences (p = 0.68 and p = 0.71). 'Active' and 'non-active' SPMS patients had a similar risk of achieving disability milestones, suggesting that progression is primarily attributed to PIRA and only to a small extent to disease activity. [ABSTRACT FROM AUTHOR]

Appropriate status epilepticus (SE) management is key to minimize admission to the pediatric intensive care unit (PICU). We retrospectively describe 115 children admitted to the PICU of the tertiary-care referral hospital of Padova for seizures, SE, and SE-related complications (59% from second-level hospitals, 41% from the referral hospital) and compare SE management among hospitals. Compared with the referral center, in second-level hospitals, anesthetics were more often administered as first/second drug (P <.001), and intubation was more frequent (P <.001). Intubation was significantly associated with SE onset at home (P =.045) and benzodiazepine-associated respiratory depression (P =.044). There was no association between intubation and SE duration, etiology, PICU length of stay, and morbidity at discharge. In conclusion, adherence to treatment protocols on SE management after the first-line drug differs between referral center and second-level hospitals. Lack of association with SE characteristics and patient's outcome suggests PICU admission could be due to inappropriate invasive management. [ABSTRACT FROM AUTHOR]

To determine whether early versus delayed autotransplantation are associated with adverse outcomes in patients undergoing renal autotransplantation. Patients who underwent renal autotransplantation from June 2012 to September 2022 were divided into 2 groups based on timing of autotransplant in relation to initial intervention or diagnosis (early cohort: ≤1-year; delayed cohort: >1-year). Primary outcomes were perioperative complications, aborted surgery, renal function (glomerular filtration rate [GFR]), and postoperative complications at most recent follow-up. Autotransplantation patients (N = 72) were predominantly female (68%) and White (54%), with a median age of 49 years. Ninety percentage of patients had undergone previous interventions, including stenting (40%) and nephrostomy tubes (49%), primarily for obstruction (64%). Early versus delayed cohorts had median preoperative disease durations of 143 (IQR 83-222) versus 673 days (IQR 529-1703, P <.001), with similar median follow-up times (879 vs 818 days, P =.8). Groups were similar in demographics and comorbidities. There were no significant differences in rates of aborted surgery (15% vs 4.2%, P =.3), perioperative complications (15% vs 17%, P >.9), long-term complications (49% vs 48%, P >.9), or changes in GFR (median change +3 vs +4, P =.7). Outcomes were comparable across preoperative disease durations ranging from 6 to 24 months. These findings were confirmed following adjustments for sex, body mass index, American Society of Anesthesiologists classification, race, preoperative creatinine levels, laterality, gastroesophageal reflux disease, diabetes, hypertension, nephrolithiasis, hyperlipidemia, history of colon surgery, urologic surgery, abdominal surgery, and prior interventions in separate logistic models. Disease duration before autotransplantation does not influence outcomes, offering reassurance for clinical decision-making in complex cases. [ABSTRACT FROM AUTHOR]

Purpose: The COVID-19 pandemic impacted healthcare delivery, especially for people with chronic disease. We investigated telehealth use by persons with multiple sclerosis (MS) during the COVID-19 pandemic and their suggestions to improve their telehealth experience. Methods: From persons with MS, we collected data on demographic, disease-related and social determinants of health, telehealth use during the COVID-19 pandemic, satisfaction with telehealth, and suggestions to improve telehealth. We conducted univariate log-binomial regression to establish factors associated with telehealth use versus no use, summarised experiences and suggestions for improvement with frequency tables, and conducted thematic analysis on free-text suggestions for improvement. Results: Of 1,485 participants, 69.8% used telehealth during the first phase of the COVID-19 pandemic. Only small differences were observed for demographic, disease and social health determinants between telehealth users and non-users. Most participants who used telehealth had good or very good experiences (new providers:74.3%; existing providers:78.6%). The most common suggestion for improving telehealth experience was "guidance on preparing for telehealth sessions." Participants also wanted expansion in telehealth availability and utility. Conclusion: Persons with MS in Australia commonly used telehealth during the COVID-19 pandemic and were generally satisfied with their experiences. Implementing the suggested improvements will help optimise telehealth for persons with MS. Registration: N/A. IMPLICATIONS FOR REHABILITATION: Australians with multiple sclerosis (MS) had good or very good experiences of telehealth during the first year of the pandemic. Telehealth is a useful consultation tool for many rehabilitation professions and may be appropriate for use across the whole MS population. To improve the delivery of rehabilitation through telehealth, provision of better guidance on preparing for telehealth consultations and provision of digital equipment to monitor their health is wanted by persons with MS. Rehabilitation professionals and researchers should take opportunities to identify if proficiency in the English language and cultural background may influence experiences with telehealth in persons with MS. [ABSTRACT FROM AUTHOR]

Introduction: It has been recently acknowledged that deficits in experiencing and processing one's own emotions, also termed alexithymia, may possibly feature the frontotemporal-spectrum disorders. This study aims to determine whether alexithymia could be included within the frontotemporal syndromes of amyotrophic lateral sclerosis (ALS). Methods: Alexithymic traits were estimated in a cohort of 68 non-demented ALS patients with the 20-item Toronto Alexithymia Scale (TAS-20). Patients were assessed for the identification of motor-phenotypes and frontotemporal syndromes based on current classification criteria. Spearman's coefficients explored the correlates of TAS-20 measures with motor-functional profiles, global cognitive, social-cognitive (emotion recognition and empathy) and behavioral status. Results: Abnormal TAS-20 scores were found in 13% of patients, and their distribution did not vary within motor and frontotemporal phenotypes. Significant associations were detected between TAS-20 and executive (p ≤.011), memory (p =.006), state-anxiety (p ≤.013) and depression measures (p ≤.010). By contrast, TAS-20 scores were unrelated to social-cognitive performances, dysexecutive and apathetic profiles. Disease duration was the only motor-functional feature being related to the TAS-20 (p ≤.008). Conclusions: Alexithymia of potential clinical relevance occur in a minority of ALS patients, and its neuropsychological correlates mostly resemble those featuring the general population. Hence, it is unlikely that alexithymia is a specific feature of frontotemporal-spectrum characterizing ALS, rather it could be an expression of psychogenic factors as a reaction to the disease. [ABSTRACT FROM AUTHOR]

Introduction: Clinical remission is the main target in the management of patients with rheumatoid arthritis (RA). However, several authors found synovitis in patients with RA in clinical remission at ultrasonography (US). Upadacitinib is a selective Janus kinase 1 inhibitor that achieved significantly higher remission rates than adalimumab and abatacept in patients with RA. Here we present the 24-week data of the UPAdacitinib Rheumatoid Arthritis REmission UltraSonography (UPARAREMUS) study. Methods: This is a longitudinal multicenter observational study, enrolling bio-naïve and bio-inadequate responder patients affected by RA. The primary endpoint was the proportion of patients achieving both clinical and US remission at week 24. The proportion of patients achieving clinical remission with different composite indexes at week 12 and 24 was also evaluated. US of four target joints (wrists and second metacarpophalangeal bilaterally) was performed at baseline and weeks 12/24, and US remission was defined as the absence of power Doppler (PD) signal ≥ 2 in one target joint, or PD ≥ 1 in two target joints. Results: After 12 weeks and 24 weeks, 40% and 63.6% of patients achieved US plus clinical remission. The following parameters were associated with US plus clinical remission: being bio-naïve and having a shorter disease duration, although at multivariate analysis significant odds ratio (OR) was found only for being bio-naïve. Conclusions: UPARAREMUS is the first study evaluating the efficacy of upadacitinib in reaching both clinical and US remission in patients with RA. At 24 weeks, 63.6% of patients reached the primary endpoint, the only baseline associated parameter was being bio-naïve. [ABSTRACT FROM AUTHOR]

Background and purpose: The amplitude, timing, and determinants of improvement with available treatments are uncertain in chronic inflammatory demyelinating polyneuropathy (CIDP). Our primary objective was to quantify categorized outcomes with routine care. Methods: We retrospectively studied treatment response within 36 months from initiation in 112 consecutive subjects with CIDP. Response was classified into a proposed new "CIDP treatment‐response category" (CT‐RC), based on achieved endpoints. Determinants of the CT‐RC, of timing of maximum improvement, and of treatment discontinuation were ascertained. Results: The CT‐RC demonstrated high concurrent validity with current outcome measures. Thirty‐six subjects (32.1%) achieved a "complete response," 37 (33%) a "good partial response," 10 (8.9%) a "moderate partial response," and 15 (13.4%) a "poor partial response." Fourteen subjects (12.5%) were "nonresponsive." The CT‐RC was independently predicted only by age. Mean time to maximum improvement was 12.1 months (range = 1–36) and was not associated with any pretreatment covariate. Treatment discontinuation occurred in 24 of 62 (38.2%) partial responders and was only associated with shorter pretreatment disease duration. Nonresponders were older and received a similar number of treatments compared to responders. Conclusions: CT‐RC classification indicates persistent disability in >60% of treatment responders in CIDP. Timing of maximum improvement is variable, frequently delayed, and unpredictable. Treatment withdrawal without deterioration is achievable in approximately 40% of subjects and may be more likely with prompt treatment. Treatment withdrawal in partial responders and limited escalation in nonresponders suggest implication of physician‐ and patient‐related factors in suboptimal response. More effective treatments/treatment methods and better understanding of other factors influencing response are needed in CIDP. [ABSTRACT FROM AUTHOR]

Background and purpose: The co‐occurrence of amyloid‐β pathology in Parkinson's disease (PD) is common; however, the role of amyloid‐β deposition in motor prognosis remains elusive. This study aimed to investigate the association between striatal amyloid deposition, motor complications and motor prognosis in patients with PD. Methods: Ninety‐six patients with PD who underwent 18F florbetaben (FBB) positron emission tomography were retrospectively assessed. The ratio of the striatum to global (STG) FBB uptake was obtained for each individual, and patients were allotted into low and high STG groups according to the median value. The effect of STG group on regional amyloid deposition, the occurrence of motor complications and longitudinal change in levodopa equivalent dose (LED) requirement were investigated after controlling for age, sex, LED and disease duration at FBB scan. Results: The high STG group was associated with lower cortical FBB uptake in the parietal, occipital and posterior cingulate cortices and higher striatal FBB uptake compared to the low STG group. Patients in the high STG group had a higher risk of developing wearing off and levodopa‐induced dyskinesia than those in the low STG group, whereas the risk for freezing of gait was comparable between the two groups. The high STG group showed a more rapid increase in LED requirements over time than the low STG group. Conclusions: These findings suggest that relatively high striatal amyloid deposition is associated with poor motor outcomes in patients with PD. [ABSTRACT FROM AUTHOR]

Critics of the ESPGHAN guidelines on CD question the acceptance of the no-biopsy policy by patients and parents against the backdrop of a lifelong diagnosis. The aim of this study was to investigate the impact of the no-biopsy approach on dietary adherence and health-related quality of life (HRQOL). In this retrospective cohort study, patients ≤ 18 years diagnosed with CD between 2007 and 2017 were sent two questionnaires: a dietary interview and a CD-specific HRQOL questionnaire (CDDUX). Included patients were divided into group A (with biopsies <2012), B (with biopsies >2012) and C (without biopsies >2012). Fisher exact test and ANOVA were used to analyze the impact of the new diagnostic strategy. Forty-seven percent (82/173 patients) consented to participate in the study. Of them, 63% had a biopsy-confirmed diagnosis (40% before 2012 (group A), 23% after 2012 (group B)), and 37% were diagnosed without biopsies (group C). Dietary compliance was similar in all groups (p = 0.67). Group A scored significantly better on the subscale 'Having CD' compared to both groups diagnosed after 2012 (p = 0.003). Group A and group C seemed to score better on the total CDDUCX score when compared to group B (86 and 80% versus 61% respectively, p = 0.13). This was also observed within the subscale Diet; Group A and C scored significantly better than group B (62 and 72% versus 39% respectively, p = 0.09). Conclusions: Omitting duodenal biopsies in the diagnostic approach of our CD cohort had no adverse effect on dietary adherence and HRQOL. What Is Known: • Since the publication of the ESPGHAN guideline of 2012, duodenal biopsies are no longer obligatory in the diagnostic approach of CD if IgA-antibodies for transglutaminase 2 are ≥10× ULN, endomysial antibodies are positive in a second blood sample and the patient/family agrees with the no-biopsy approach. • Literature on the effect of the no-biopsy approach on dietary adherence and HRQOL is scarce. What Is New: • Omitting duodenal biopsies does not influence dietary adherence and quality of life. • In our cohort, lower quality of life measured with the CDDUX subscale 'Having CD' is more likely to be related to shorter disease duration than to the diagnostic approach. [ABSTRACT FROM AUTHOR]

The escalating worldwide prevalence of Crohn's disease (CD) among children and adolescents, coupled with a trend toward earlier onset, presents significant challenges for healthcare systems. Moreover, the chronicity of this condition imposes substantial individual burdens. Consequently, the principal objective of CD treatment revolves around rapid inducing remission. This study scrutinizes the impact of age, gender, initial disease localization, and therapy on the duration to achieve disease activity amelioration. Data from the Saxon Pediatric IBD Registry in Germany were analyzed over a period of 15 years. In addition to descriptive methods, logistic and linear regression analyses were conducted to identify correlations. Furthermore, survival analyses and Cox regressions were utilized to identify factors influencing the time to improvement in disease activity. These effects were expressed as Hazard Ratios (HR) with 95% confidence intervals. Data on the clinical course of 338 children and adolescents with CD were available in the registry. The analyses showed a significant correlation between a young age of onset and the severity of disease activity. It was evident that treatment with anti-TNF (Infliximab) was associated with a more favorable prognosis in terms of the time required for improvement in disease activity. Similarly, favorable outcomes were observed with the combination therapies of infliximab with enteral nutrition therapy and Infliximab with immunosuppressants. Conclusion: Our analysis of data from the Saxon Pediatric IBD Registry revealed that the timeframe for improvement of disease activity in pediatric Crohn's disease is influenced by several factors. Specifically, patient age, treatment modality, and initial site of inflammation were found to be significant factors. The study provides important findings that underline the need for individualized treatment. [ABSTRACT FROM AUTHOR]

Cladribine tablets (CladT), like alemtuzumab, acts as an immune reconstitution therapy. However, CladT is administered orally (alemtuzumab is given by infusion) and without the potential for serious side effects that limit the therapeutic use of alemtuzumab in multiple sclerosis (MS). Treatment with CladT, given initially as short courses of treatment 1 year apart, provides years of freedom from MS disease activity in responders to treatment. The appearance of mild or moderate MS disease activity after the initial 2 years of treatment may prompt careful follow-up or a further course of CladT, depending on the nature of the activity and individual circumstances. The appearance of severe MS disease activity requires a switch to an alternative high-efficacy disease-modifying treatment (DMT). The accumulating data from CladT-treated people with MS in real-world studies, including those with follow-up durations extending for years beyond the initial treatment, have demonstrated long-term freedom from MS disease activity in a good proportion of patients. This clinical experience has also confirmed that treatment with CladT is generally safe and well tolerated. The best time to prescribe a high-efficacy DMT is the subject of debate, with evidence that earlier versus later use of such agents may provide more effective long-term protection from disability progression. High-efficacy DMTs have traditionally been reserved for use in people with MS and high disease activity on presentation or breakthrough disease on one or more DMTs, as per the current product labels. The latest evidence from real-world studies suggests that CladT is effective and safe in DMT-naïve patients, including those with shorter disease duration. [ABSTRACT FROM AUTHOR]

Based on the signaling hypothesis of blood glucose (BG), a rise in BG levels signals a positive energy budget for healthy individuals but cellular starvation for individuals with type 1 diabetes. We examined this novel prediction and its intervention implications in the context of delay discounting, the degree to which delayed rewards are discounted, and the regulatory effects of insulin ingestion. We recruited 44 adults with type 1 diabetes (mean age 30.8 years, diabetes duration 15.4 years) and recorded their BG levels. The delay discounting rate was measured using the intertemporal choice task, where participants were required to choose between sets of smaller-and-sooner (SS) and larger-and-later (LL) rewards. In addition, 82 age-matched healthy participants were recruited to provide a baseline comparison on delay discounting. Random forest analysis showed that among many diagnostic factors, delay discounting was most dominating in differentiating the individuals with type 1 diabetes from the control participants. A hierarchical linear mixed model revealed that participants with type 1 diabetes had a stronger preference for SS rewards (p <.001) after controlling for covariates. Participants who had insulin delivered before the last meal exhibited a stronger preference for LL rewards compared to after-meal delivery. In contrast, subjective measures (e.g., self-reported hunger) failed to predict the participants' actual BG levels and delay discounting rates. In sum, individuals with type 1 diabetes tend to discount future rewards excessively compared to the control participants. Pre-meal insulin ingestion was associated with a higher LL preference for future rewards. [ABSTRACT FROM AUTHOR]

Background: The efficacy of rituximab in steroid-resistant nephrotic syndrome (SRNS) is controversial. We previously reported that rituximab in combination with methylprednisolone pulse therapy (MPT) and immunosuppressants was associated with favorable outcomes. We determined risk factors for poor response following rituximab treatment, which remains unknown. Methods: This retrospective study included 45 patients with childhood-onset SRNS treated with rituximab across four pediatric kidney facilities. Treatment effects were categorized as complete remission (CR), partial remission (PR), and no remission (NR) at one year after rituximab treatment. The primary outcome was the rate of CR, PR, and NR. Risk factors for non-CR were calculated with multivariate logistic regression. Adverse events and the relationship between disease status at one year and long-term prognosis were also evaluated. Results: The rates of CR, PR, and NR at one year were 69%, 24%, and 7%, respectively. The median time from rituximab administration to CR was 90 days. The median follow-up period after rituximab administration was 7.4 years. In multivariate analysis, significant risk factors for poor response were the pathologic finding of focal segmental glomerular sclerosis and a long interval between SRNS diagnosis and rituximab administration. The rates of CR were 90.3% and 21.4% in patients receiving rituximab within and after 6 months following SRNS diagnosis, respectively (p < 0.001). Five patients developed chronic kidney disease stage G5, including 2 of the 11 patients with PR and all 3 patients with NR, whereas none of the 31 patients with CR developed chronic kidney disease stage G5. Conclusion: Early administration of rituximab in combination with MPT and immunosuppressants might achieve favorable outcomes in patients with SRNS. [ABSTRACT FROM AUTHOR]

The association of a single time-point measure of sleep duration with cardio-metabolic disease has been extensively studied, but few studies have focused on the impact of sleep duration trajectory. This study aims to model the sleep duration trajectory as predictors for the subsequent development of cardio-metabolic disease. This study recruited a notably large population (n = 9883) of subjects aged at least 45 years from the China Health and Retirement Longitudinal Study (CHARLS), who participated in sequential surveys conducted in 2011, 2013, 2015, and 2018. Sleep duration trajectories were plotted using data of night sleep duration recorded at intervals from 2011 to 2015 by latent class trajectory model. The onset of cardio-metabolic diseases from 2015 to 2018 were confirmed and then the risk of different sleep duration trajectories on incident cardio-metabolic disease was examined using cox proportional hazards regression model. We identified four sleep duration trajectories. Compared to the normal-stable trajectory, the short-stable trajectory was significantly associated with higher risk of incident stroke (hazard ratio [HR], 1.32; 95 % confidence interval [CI], 1.02 to 1.70), dyslipidemia (HR, 1.22; 95%CI, 1.01 to 1.49), and diabetes (HR, 1.42; 95%CI, 1.13 to 1.78) within three years of follow-up, and the short-increasing trajectory predicted a higher risk of incident stroke (HR, 2.38; 95%CI, 1.25 to 4.55). Short sleep trajectory could increase the risk of incident stroke, dyslipidemia, and diabetes, and an increasing sleep trajectory was associated with increased risk of incident stroke among middle-aged and older Chinese adults. • This investigation provided novel insights of sleep duration trajectories among middle-aged and older Chinese adults. • Short sleep trajectory increased the risk of incident stroke, dyslipidemia, and diabetes. • Maintaining long-term stable and moderate sleep duration are recommended to prevent cardio-metabolic disease. [ABSTRACT FROM AUTHOR]

Internalized HIV-related stigma (IHS) among people living with HIV (PLHIV) has been documented as one of the factors contributing to the ongoing AIDS epidemic. The purpose of this study, which was conducted from September 2021 to January 2022, was to measure prevalence and identify factors associated with IHS among research participants who were living with HIV recruited from a research clinic in Chiang Mai, Northern Thailand. Participants were considered to have IHS if they agreed to at least one of the 8 items of the newly developed Thai Internalized HIV-related Stigma Scale (Thai-IHSS). Of the 104 participants, 65.4% were female. The median age was 51.5 years and the duration of known HIV infection was 19.0 years. Fifty-three percent of the participants had IHS as defined by the study. Reduced probability of having IHS was independently associated with certain levels of education (middle or high school education compared with no or primary school) (AOR = 0.30; 95% CI: 0.12–0.77) and increased mental health-related quality of life (AOR = 0.39; 95% CI: 0.18–0.86). The prevalence of IHS among PLHIV in Chiang Mai was high. These findings highlight the requirement for comprehensive mental health care programs for PLHIV to improve their quality of life. [ABSTRACT FROM AUTHOR]

Purpose: To investigate effectiveness of the ABCDEF bundle to manage and prevent delirium. Background: ICU delirium is a common hospital problem that 80% of critically ill patients in the ICU experience. The ABCDEF bundle is one of the tools that included in Delirium guidelines to manage critically ill patients. Research design: Pre- and post intervention a quasiexperimental design was utilized in the present study. Setting: This study was conducted in the intensive care units of Assiut University Hospital. Methods: A total of 60 mechanically ventilated patients were recruited using inclusion and exclusion criteria. The ABCDEF bundle was implemented every day for the first 7 days of ICU admission, and patient sedation and delirium status were assessed using the Confusion Assessment Method for the Intensive Care Unit (CAMICU). Sedation instrument measures were utilized in data collection. Results: Significant differences were found in the incidence of delirium: 20% in the study group versus 70% in the control group. The increased mean of days without delirium ICU stay was 4.6333 in the study group and 1.1000 in the control group, with P value = .001. Conclusion: The mechanically ventilated patients exposed to the implementation of the ABCDE bundle experienced fewer delirium signs than before the ABCDE bundle was implemented. [ABSTRACT FROM AUTHOR]

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BACKGROUND: Firefighting is recognised as a physically demanding occupation involving exposure to hazardous environments and activities. An aging workforce combined with the age-related decline in physical fitness may result in increased future workers' compensation expenditure for fire service organisations. OBJECTIVE: The objective of this research was to investigate the costs associated with musculoskeletal sprain and strain injury and the impacts of age and injury location on Workers' Compensation claims submitted by professional urban firefighters. METHODS: Claim rates, direct costs, and days lost were extracted from a professional Fire Service organisation's workers' compensation claim database for financial years between 2011 to 2018. RESULTS: The mean cost per claim increased with age, with a mean claim cost of the 60–70-year-old group over 10 times more than the 20–29-year-old group. The mean days lost per claim were also higher for claims submitted by firefighters aged over 50. CONCLUSIONS: Older firefighters miss more workdays when injured and are associated with increased claims costs, particularly those in the 60–70-year group. With an aging workforce, Fire Service organisations must implement appropriate management and prevention strategies to reduce the potential risks associated with an aging workforce. [ABSTRACT FROM AUTHOR]

Objective. To evaluate the relevance of the Rheumatoid Arthritis Impact of Disease (RAID) score as a disease activity marker of rheumatoid arthritis (RA) in a teleconsultation setting. Methods. A prospective, observational, 24-month, single-center study involving patients with RA who underwent teleconsultations was performed. The RAID score was sent to all patients by email and completed the day before the scheduled session. The RAID questionnaire was also completed just prior to the next scheduled face-to-face consultation. The same physician performed teleconsultation/in-person consultations and was unaware of the RAID results. Results. We included 70 patients (mean age 50 [SD 14] yrs, mean disease duration 10 [SD 9] yrs). The RAID score correlated with the following items: patient global assessment (r 0.55, P < 0.001), patient-reported swollen joint count (r 0.50, P < 0.001), and Disease Activity Score in 28 joints based on C-reactive protein (DAS28-CRP) calculated with patient self-reported tender/swollen joints (r 0.74, P < 0.001). The RAID score completed during the next face-to-face consultation for 45 patients also correlated with the DAS28-CRP performed by the clinician (r 0.65, P < 0.001). A RAID score > 2 was associated with the best combination of sensitivity (94%) and specificity (43%) for the indication of rapid in-person consultation because of insufficiently controlled disease activity, with an area under the curve of 0.74. All 23 patients with RAID < 2 had no intercurrent flares; overall physician global assessment was 1.6 of 10 (SD 1.4), DAS28-CRP 1.5 (SD 0.2), and CRP 1.8 (SD 1.4) mg/L. Conclusion. Our findings reinforce the RAID score as a valuable tool in teleconsultation, exhibiting a good correlation with disease activity variables. Using a RAID score threshold of 2 during teleconsultations could distinguish patients with good disease control and those with the potential need for an in-person visit. [ABSTRACT FROM AUTHOR]

Purpose: During the coronavirus disease 2019 pandemic, health services offered to individuals diagnosed with mental disorders were interrupted, and use of alternative methods, such as telenursing, came to the forefront. Method: Sixty-four individuals with schizophrenia participated in the current randomized controlled trial that evaluated whether a telenursing intervention affected their drug attitudes, self-efficacy, and quality of life. Pretest, posttest, and follow-up measurements were obtained for experimental and control groups from May to August 2021. Data were collected via a Personal Information Form, Drug Attitude Inventory-10, Self-Efficacy Scale, and World Health Organization Quality of Life Questionnaire–Short Form. Results: Upon comparison of scores obtained by the experimental and control groups in pretest, posttest, and follow-up measurements, it was discerned that telenursing positively affected drug attitudes of participants in the experimental group and enhanced their quality of life. Although there was an increase in self-efficacy levels of the experimental group compared to the control group, the difference was not statistically significant. Conclusion: Telenursing is an effective intervention for the improvement of drug attitudes and quality of life but is not satisfactory for the improvement of self-efficacy in individuals with schizophrenia. [Journal of Psychosocial Nursing and Mental Health Services, 62(10), 15–24.] [ABSTRACT FROM AUTHOR]

Improving health-related quality of life (QoL) is crucial for managing Parkinson's disease. However, QoL outcomes after deep brain stimulation (DBS) of the subthalamic nucleus (STN) vary considerably. Current approaches lack integration of demographic, patient-reported, neuroimaging, and neurophysiological data to understand this variability. This study used explainable machine learning to analyze multimodal factors affecting QoL changes, measured by the Parkinson's Disease Questionnaire (PDQ-39) in 63 patients, and quantified each variable's contribution. Results showed that preoperative PDQ-39 scores and upper beta band activity (>20 Hz) in the left STN were key predictors of QoL changes. Lower initial QoL burden predicted worsening, while improvement was associated with higher beta activity. Additionally, electrode positions along the superior-inferior axis, especially relative to the z = −7 coordinate in standard space, influenced outcomes, with improved and worsened QoL above and below this marker. This study emphasizes a tailored, data-informed approach to optimize DBS treatment and improve patient QoL. [ABSTRACT FROM AUTHOR]

Aims: The urinary dysfunction in multiple system atrophy (MSA) is characterized by large post-void residuals (PVR) due to impaired bladder contractility. However, the evaluations of bladder contractility are not well validated in MSA. Because the bladder contractility index can be generally represented as Pdet Qmax (detrusor pressure at maximum urinary flow rate) + kQmax (maximum urinary flow rate), we aim to examine which "k" value is suitable for representing bladder contractility concerning its correlations to PVR and voided percentage (VOID%). Methods: We retrospectively reviewed 133 patients with MSA (74 males, 59 females, mean disease duration 3.2 years) who underwent an urodynamic study. We calculated bladder contractility using the formula PIPk = Pdet Qmax + kQmax by increasing the "k" value from 0.1 to 10 by increments of 0.1. We calculated the correlations between each PIPk (k = 0.1-10.0) and PVR and VOID%. Results: The correlational coefficients between PIPk and VOID% were larger than those between PIPk and PVR. The correlational coefficients between PIPk and VOID% reached a plateau level at a "k" value >5.0 in male patients, suggesting that currently used formulas such as Pdet Qmax + 5Qmax for males might be appropriate for male MSA patients. However, the correlational coefficients between PIPk and VOID% reached a plateau level in female patients when the "k" values were >6.0, which might overestimate bladder contractility in female patients. Conclusion: Although currently used formulas such as Pdet Qmax + 5Qmax might be appropriate for male MSA patients, formulas for female patients need further evaluation. [ABSTRACT FROM AUTHOR]

Background: Farmers with chronic obstructive pulmonary disease (COPD) often face both respiratory issues and psychological distress, which can exacerbate their condition. However, no prior research has examined how the frequency of respiratory symptoms is associated to psychological distress in these individuals. Therefore, this study aimed to explore this relationship among U.S. farmers living with COPD. Methods: A cross-sectional study involved 101 participants, a mix of on-site and online recruits, assessing respiratory symptoms and psychological distress in farmers with COPD. The study employed standard self-reported measures and utilized both simple and multiple linear regression to analyze the association between respiratory symptoms and psychological distress. Findings: Participants reported notably higher levels of respiratory symptoms (61.6 [ SD = 13.3]) compared to the reference score of 12, along with elevated psychological distress (25.9 [ SD = 10.6]). Factors like COPD duration, income, smoking, and emergency department (ED) visits correlated with respiratory symptoms, while age, COPD duration, income, smoking, pesticide exposure, and farm type were associated to psychological distress. Notably, even after accounting for age, smoking, and pesticide exposure, a significant association remained between respiratory symptoms and psychological distress (β = 0.46, p <.001). Conclusion: Respiratory symptoms were significantly associated to psychological distress, even when considering other factors. While this aligns with existing research, a future longitudinal study is crucial to establish the cause-effect relationship between these variables. Understanding this relationship could inform the development of targeted interventions to alleviate psychological distress in individuals with respiratory symptoms. Implications for Occupational Health Nursing Practice: The correlation between COPD symptoms and psychological distress in farmers emphasizes the need for integrated nursing care. Occupational health nurses should prioritize combined respiratory and mental health assessments. [ABSTRACT FROM AUTHOR]

Background and Purpose Methods Results Conclusions Pure autonomic failure (PAF) presents primarily as cardiovascular autonomic failure and may phenoconvert to other neurodegenerative disorders. However, the involvement of other autonomic functions has been poorly evaluated. This study aims to characterize genitourinary and bowel dysfunction and explore their relationship with cardiovascular autonomic dysfunction.Pure autonomic failure patients underwent cardiovascular autonomic testing and an assessment of pelvic autonomic dysfunction using urinary, sexual symptoms questionnaires and a bladder diary. Demographic, clinical features and related medical comorbidities were assessed.Twenty‐five patients (10 males) with PAF were included (mean age 71 ± 8 years; disease duration 13 ± 8 years). 96% (24/25) reported lower urinary tract symptoms, of which overactive bladder symptoms were most commonly reported (n = 23; 92%; median overactive subscore 8, interquartile range [IQR] 3–11), followed by voiding difficulties (n = 19; 76%; median low stream subscore 2, IQR 1–3) using the Urinary Symptom Profile; however, only four (16%) required clean intermittent self‐catheterization. Sexual dysfunction was common (n = 21; 84%) using the Arizona Sexual Experience Scale. Mild faecal incontinence and constipation were reported. 86% (19/22) had nocturnal polyuria (NP) and the median NP index was 47% (IQR 38%–51%; normal range <33%). 77% (10/13) had voiding dysfunction and 31% (4/13) had post‐void residual urine >100 mL. There were no significant correlations between the need for catheterization and the degree of NP with age, disease duration and cardiovascular autonomic parameters (p > 0.05).Nocturnal polyuria, genitourinary and bowel symptoms are commonly seen in PAF. The pathophysiology of NP in PAF is most likely multifactorial and may occur independent of cardiovascular autonomic failure. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to compare the salivary gland ultrasonography(SGUS) findings in patients with primary Sjögren's Syndrome (pSS) and diabetes mellitus(DM) patients with sicca symptoms and to examine the relationship between salivary gland ultrasonography (SGUS) findings with clinical and laboratory parameters. Methods: In this study, 34 patients with pSS and 34 DM patients with sicca symptoms were included. In all patients, bilateral parotid, and submandibular gland ultrasonography (totally 272 glands) was performed by blinded rheumatologist, using the Hocevar and the Outcome Measures in Rheumatology (OMERACT) scoring system. Clinic and ultrasonographic variables were compared between groups. The association between SGUS score and disease duration was analyzed by correlation analysis. Results: Patients with pSS presented significantly higher SGUS scores than patients with DM (the Hocevar score; 20.93(± 9.65) vs. 3.82(± 3.71); p < 0.05, the OMERACT score; 5.96(± 2.30) vs. 2.07(± 1.65); p < 0.05, respectively). In patients with pSS, the submandibular gland scores were significantly higher than the parotid gland scores (right; p < 0.05 vs. left; p < 0.01) while DM patients showed significantly higher parotid gland scores (right; p < 0.05 vs. left; p < 0.05). In pSS patients, the SGUS scores were associated with disease duration (r = 0.57; r = 0.50; p < 0.05), symptom duration (r = 50; r = 0.47; p < 0.05), and the European League Against Rheumatism Sjögren's Syndrome Patient Reported Index (ESSPRI)-dryness score (r = 0.35, r = 0.36; p < 0.05). However, in DM patients, the SGUS scores are highly correlated with the ESSPRI-dryness (r = 0.74, r = 0.72; p < 0.05) and HbA1C level (r = 0.91, r = 0.86; p < 0.05). Conclusions: This study demonstrated that major salivary gland involvement was more severe and correlated with disease duration, and submandibular gland was dominantly affected in pSS. Contrarily, in DM patients, salivary gland involvement was milder, parotid dominant and related to level of dryness and HbA1C, rather than disease duration when compared to pSS, [ABSTRACT FROM AUTHOR]

ABSTRACT Objectives Study Design Results Conclusions To analyse the correlation between temporomandibular joint (TMJ) disc perforation and degenerative joint changes (DJC) on cone‐beam computed tomography (CBCT) and related factors.A total of 238 female patients with anterior disc displacement without reduction (ADDwoR), accounting for 348 affected joints, requiring TMJ disc open anchorage surgery were included in the study conducted from June 2021 to August 2022. Following TMJ disc open anchorage surgery, patients were divided into two groups: disc perforation (DP) and disc non‐perforation (DNP). CBCT was utilised to assess different grades of condyle and articular eminence degenerative changes, and comparisons were made between the two groups regarding DJC and clinically relevant factors.In comparison with the DNP group, the DP group exhibited statistically significant differences in mid‐ and late‐stage condyle bone degenerative changes and bone alterations of the articular eminence (odds ratio [OR] = 7.822; 95% CI [4.438–13.785]; p < 0.001 and OR = 5.575; 95% CI [3.128–9.936]; p < 0.001). Additionally, persistent joint sounds (OR = 1.932; 95% CI [1.011–3.691]; p = 0.046) and longer disease duration (OR = 4.901; 95% CI [2.395–10.028]; p < 0.001) demonstrated statistically significant differences. However, no significant differences were observed between the two groups in terms of age, joint pain and limited mouth opening.Bone degeneration changes in TMJ CBCT images are a high possible risk factor for DP. With an escalation in the degree of condyle degeneration, the risk of DP may increased correspondingly. Persistent joint sounds and extended duration of the disease were also confirmed to be noteworthy clinical risks of DP. [ABSTRACT FROM AUTHOR]

AbstractCytotoxic T-lymphocyte associated antigen-4 (CTLA-4) is a costimulatory receptor exhibiting a potent inhibitory signal on antigen-activated immune responses. A soluble form, sCTLA-4, has been identified and was found to be increased in several autoimmune diseases. We aimed to evaluate serum levels of sCTLA-4 in different immune cytopenias, and to determine its possible relation to the disease activity. We measured serum levels of sCTLA-4 in 47 patients with immune cytopenias and compared them to 47 age- and sex-matched healthy controls. sCTLA-4 levels were significantly higher in patients with immune cytopenias compared to healthy controls (p < 0.001), however, levels were comparable between different groups of immune cytopenias (p = 0.084). Serum sCTLA-4 inversely correlated with age at diagnosis and hemoglobin level (p = 0.048, and p = 0.039 respectively), while it directly correlated with disease duration (p = 0.023) as well as markers of hemolysis including reticulocyte count, serum LDH and indirect bilirubin (p = 0.025; p = 0.019; p = 0.004 respectively). In the AIHA group, serum sCTLA-4 levels were significantly lower in patients in remission compared to patients with active disease (p = 0.026). Children with immune cytopenia exhibit significantly higher levels of circulating sCTLA-4 which correlated with disease activity, yet the prognostic significance and its use to tailor treatment regimen require additional studies. [ABSTRACT FROM AUTHOR]

Alopecia areata (AA) is a common chronic relapsing nonscarring alopecia. Severe forms of AA commonly manifest during childhood. Treatment of AA is challenging due to the variability of the disease course as well as unpredictable responses to treatment. There is no uniform approved treatment for cure or sustained remission in children till now. Tofacitinib emerged as a novel drug in the treatment of AA, but few studies have been conducted on its safety and efficacy in children. Limitation of this study includes retrospective nature, small sample size, and lack of prolonged follow‐up. Aim. This retrospective study aimed to assess the efficacy and safety of oral tofacitinib in children with AA. Method. In this retrospective study, we included patients aged 18 years or younger with AA. The scalp blandness of included patients was greater than 20% and they were on oral tofacitinib for at least two months. The demographic data, clinical characteristics, tofacitinib efficacy, and adverse effects were recorded. The primary endpoint was the last recorded percent change in the Severity of Alopecia Tool (SALT) score during treatment. Results. We included 26 patients (12 males and 14 females) with AA with a mean age of 11.6 ± 4.42 (3–18) years. Eighteen of them were in the alopecia areata (AA) group, whereas eight patients had alopecia totalis (AT) or alopecia universalis (AU). The mean disease duration before starting treatment with tofacitinib was 3.9 ± 3.3 years. Most of the patients were on a tofacitinib daily dose of 5 mg (53.85%) and 10 mg (38.46%). Patients were on tofacitinib for 6.73 ± 3.79 months. The patients' baseline SALT score was recorded as 68.58 ± 32.65 and the final SALT score was 17.65 ± 23.88. Thus, the patients achieved a 50.92% reduction in the SALT score. Interestingly, there were no statistically significant differences in clinical efficacy between subtypes of AA and AT/AU. Conclusion. Tofacitinib was significantly effective in treating AA and AT/AU in children, with mild tolerable adverse effects, although relapse during treatment and tapering was recorded. Future randomized clinical trials with longer follow‐up periods are needed to evaluate the safety of oral tofacitinib in children. [ABSTRACT FROM AUTHOR]

\n Pain fluctuations are a characteristic phenomenon in advanced Parkinson’s disease (PD), but their temporal association with motor and non-motor symptom (NMS) fluctuations remains largely enigmatic. Moreover, data on their importance for disease severity perception and health-related quality-of-life (hr-QoL) is limited.To dissect pain fluctuations with respect to pain type and frequency patterns, and their association with motor and non-motor fluctuations.Prospective observational cohort study in advanced PD assessing symptom fluctuations by simultaneous hourly ratings using the PD Home diary (Off, On, Dyskinetic state), a pain diary (assessing 9 pain types) and a non-motor diary (10 key NMS) based on validated instruments.Forty-seven out of 55 eligible participants with fluctuating PD (51% men, median age 65, median disease duration 10 years) had sufficient datasets (>95% of hours) from 2 consecutive days. Pain was reported in 35% of waking hours with clear circadian rhythm peaking in early morning Off periods and clustering during motor Off state (49% of Off state hours with pain). Main NMS co-fluctuating with pain were “Fatigue” and “Inner Restlessness”. Simultaneous assessment of global disease severity by participants revealed that pain was associated with worse disease severity only in motor On and Dyskinetic state but not in Off state, which translated into significant correlations of daily pain times with hr-QoL only during motor On and Dyskinetic state.Aside from treating motor Off periods, specific recognition of pain particularly during motor On and Dyskinetic state comprises an important aspect for disease management in advanced PD.Oscillations of the frequency and severity of pain over the day (also called pain fluctuations) are common in advanced Parkinson’s disease (PD). However, their relationship with oscillations of motor and other non-motor symptoms remains unclear. Moreover, only very little data exists on how pain impacts disease severity perception and quality of life for the patients. The present study thus aimed to better understand pain fluctuations and their association with motor and non-motor symptoms in advanced PD. We conducted a prospective observational cohort study in advanced PD patients. Participants rated their symptoms hourly on two consecutive days using three diaries: the PD Home diary (for motor fluctuations), a pain diary (assessing several pain types), and a non-motor diary covering 10 key non-motor symptoms. Pain occurred during 35% of waking hours with a clear circadian rhythm peaking in the early morning and clustering during motor “Off” states as characterized by pronounced motor symptoms. The main non-motor symptoms associated with pain were “Fatigue” and “Inner Restlessness.” Interestingly, pain severity correlated with health-related quality of life only during motor “On” state (defined as a state with good mobility and motor function) and “Dyskinetic” state characterized by the occurrence of involuntary movements, but not during motor “Off” periods. In conclusion, in managing advanced PD, recognizing pain during motor “On” and Dyskinetic states is crucial beyond just addressing motor “Off” periods. This understanding can significantly impact disease management and improve patients’ quality of life. [ABSTRACT FROM AUTHOR]

Background: Patients with type 2 diabetes mellitus (T2D) have an increased risk of vascular complications. Despite the rise in the prevalence of T2D and its complications throughout the globe, there is a paucity of data regarding the prevalence and determinants of vascular complications of T2D in Ethiopia. Hence, this study aimed to assess the prevalence, patterns, and determinants of the microvascular and macrovascular complications of T2D among adult patients attending a teaching hospital in Addis Ababa, Ethiopia. Methods: A retrospective study was done by reviewing the electronic health records of adult patients with T2D attending the general medical and endocrine referral clinics of Yekatit 12 Hospital Medical College, Addis Ababa, Ethiopia, from June 1, 2023, to November 30, 2023. Statistical Package for Social Sciences (SPSS), version 25, was used to analyze the data. Descriptive analysis was used to summarize the sociodemographic, clinical, and laboratory profiles as well as the patterns of vascular complications of T2D. Bivariate and multivariate logistic regression models were fitted, and the crude odds ratio (COR) and adjusted odds ratio (AOR), together with the 95% confidence interval (CI), were computed to identify the determinants of microvascular and macrovascular complications of T2D. Results: A total of 272 patients with T2D were included in this study; 50.5% were females, and the mean (± standard deviation) age was 56.3 ± 12.8 years. The majority of patients (62.5%) had diabetes for ≥ 5 years. More than half (51.5%) had poor glycemic control with glycated haemoglobin (HbA1c) value of ≥ 7%. The overall prevalence of vascular complications was 39%. The prevalence of microvascular complications was 23.5%, the most common being neuropathy (11.8%), and the prevalence of macrovascular complications was 21%, the most common being coronary artery disease (12.1%). The determinants of microvascular complications were age ≥ 60 years (AOR = 2.25, 95% CI: 1.17, 4.33), diabetes duration of ≥ 5 years (5–10 years [AOR = 3.13, 95% CI: 1.37, 7.18], and > 10 years [AOR = 3.88, 95% CI: 1.66, 9.06], and HbA1c value of ≥ 7% (AOR = 2.21, 95% CI: 1.14, 4.28). The odds of developing macrovascular complications were higher with diabetes duration of ≥ 5 to 10 years (AOR = 2.89, 95% CI: 1.37, 6.12) as compared with diabetes duration of < 5 years. Conclusions: This study demonstrated a high prevalence of microvascular and macrovascular complications in adult patients with T2D. Older age, prolonged duration of diabetes, and poor glycemic control were identified as the determinants for the development of microvascular complications of T2D, while prolonged duration of diabetes was the determining factor for the development of macrovascular complications. Hence, targeted initiatives are required to enhance the prevention and early detection of vascular complications of T2D in resource-limited countries like Ethiopia. [ABSTRACT FROM AUTHOR]