Longer Disease Duration Research Articles

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

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

Correlates of malnutrition in patients with heart failure: the role of social support.

Heart failure (HF) is a major public health challenge. Malnutrition has a significant effect on HF prognosis. Understanding the impact of social and clinical factors on the risk of malnutrition is necessary because it may aid in improving the health status of HF patients. Three hundred twenty patients with HF who were hospitalized in a heart centre in Shiraz, Iran, from March to November 2022 were studied. Two validated questionnaires were used to evaluate malnutrition and social support: (1) Mini-Nutritional Assessment Short Form and (2) Medical Outcomes Study Social Support Survey. The participants were then divided into three groups: those with normal nutritional status (scores 12-14), those at risk of malnutrition (scores 7-11), and those who were malnourished (scores 0-6). The potential correlates of malnutrition (including socio-demographic, clinical, comorbidities, and laboratory factors) were included in the study. Then, ordinal logistic regression was used to investigate the correlates of malnutrition. The mean age of the participants was 64.2±11.2years, and more than half were male and married. Normal nutritional status was seen in 110 (34.4%) participants, 151 (47.2%) were at risk of malnutrition, and 58 (18.1%) were malnourished. The mean social support score of the participants was 61.65±12.91. According to the adjusted odds ratios (95% confidence intervals) obtained from multivariate analysis, increased risk of malnutrition was associated with having a lower social support score [0.95 (0.93-0.97), P-value≤0.001], lower body mass index [0.91 (0.86-0.97), P-value=0.004], higher New York Heart Association classification [1.26 (1.02-1.56), P-value=0.03], longer duration of disease [1.006 (1.001-1.01), P-value=0.006], and lower serum albumin level [0.25 (0.08-0.75), P-value=0.01]. Besides the clinical conditions affecting the risk of malnutrition in patients with HF, social support may play an important role. Including this factor in HF guidelines and developing educational programmes may help improve HF patients' health.

The clinical spectrum of MELAS and associated disorders across ages: a retrospective cohort study.

Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) is a severe multisystemic disease, although some have a milder phenotype. We aimed to evaluate the clinical spectrum of this disease from MELAS patients to asymptomatic carriers and identify predictors of severity. We reviewed 81 patients, who had MELAS or had positive genetics without meeting clinical criteria. Patients who met criteria including lactic acidosis, encephalomyopathy, and stroke-like episodes (SLE) were categorized as MELAS, symptomatic non-MELAS, and asymptomatic. MELAS was further categorized as "standard-onset" if the first stroke-like episode (SLE) occurred before age 40 or "late-onset." Eighty-one patients were included: 42 MELAS (13 late-onset), 30 symptomatic non-MELAS, and 9 asymptomatic. MELAS patients had lower BMI at onset (mean 18.6 vs. 25.1 asymptomatic and 22.0 symptomatic non-MELAS, p < 0.05). There was a trend toward higher serum heteroplasmy in MELAS compared to symptomatic non-MELAS and asymptomatic (means 39.3, 29.3, and 21.8% p = 0.09). Symptomatic non-MELAS had more sensorineural hearing loss as first presenting symptom (51.6% vs. 24.4%, p < 0.05). MELAS had higher prevalence of seizures (88.1% vs. 16.7%, p < 0.05) and shorter survival from onset to death (50% mortality at 25 years vs. 10%, p < 0.05). Late-onset MELAS had longer disease duration from first symptom to first SLE (mean 16.6 vs. 9.3 yrs) and also lived longer (mean age at death 62 vs. 30). Standard-onset MELAS had more neurologic involvement at onset than late-onset (51.7% vs. 15.4%). Late-onset patients had more prevalent diabetes (69.2% vs. 13.8%) and nephropathy (53.8% vs. 10.3%). Patients with late-onset MELAS also had more organ systems involved (mean 4.1 vs. 2.7, p < 0.05). There was a trend toward higher heteroplasmy levels in standard-onset (mean 44.8% vs. 25.3%, p = 0.18). Our study highlights the spectrum of MELAS. The lower BMI in MELAS at presentation as well as higher rates of sensorineural hearing loss as initial symptom in symptomatic non-MELAS may be useful clinical markers. While many patients present before age 40 with SLE, some can present with SLE later in life. Standard onset MELAS is more likely to present with neurologic symptoms. Late-onset is more likely to suffer diabetes or nephropathy and have more organ systems involved.

Male spondyloarthritis patients and those with longer disease duration have less severe disc degeneration: propensity score-matched comparison.

Using whole spine sagittal T2 MRI, we aimed to compare the severity and prevalence of disc degeneration (DD) in axial SpA patients vs the general population and to determine any association between spinal inflammation, structural changes, mobility and DD among SpA patients. Two prospectively collected cohorts of SpA patients (n = 411) and the general population (n = 2007) were recruited. Eventually, 967 participants from the populational cohort and 304 participants from the SpA cohort were analysed. Two hundred and nineteen matched pairs were generated by propensity score matching. Imaging parameters, including Pfirrmann grading, disc herniation, high-intensity zone, Schmorl's node, Modic change and anterior marrow change were studied and compared from C2/3 to L5/S1. DD was defined as Pfirrmann grade 4 or 5. Demographic factors, including age, sex and BMI, were collected. Multivariable linear regression was used to determine the association between spinal inflammation [Spondyloarthritis Research Consortium of Canada (SPARCC) spine MRI index], structural changes [modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS)] and mobility (BASMI) with lumbar Pfirrmann score. SpA patients had lower prevalence of DD (P < 0.001). The disease stage-stratified regression model showed that SPARCC spinal MRI index was associated with higher lumbar Pfirrmann scores in early disease (β = 0.196, P = 0.044), whereas mSASSS was associated with lower lumbar Pfirrmann scores in later disease (β = -0.138, P = 0.038). Males had higher mSASSS (P < 0.001) and lower odds of whole spine DD (odds ratio = 0.622, P = 0.028). SpA patients had lower DD severity than the general population. Males had higher mSASSSs, and increased mSASSS at later disease was associated with less severe DD.

The effect of doorway characteristics on freezing of gait in Parkinson's disease.

Freezing of gait is a debilitating symptom in Parkinson's disease, during which a sudden motor block prevents someone from moving forward. Remarkably, doorways can provoke freezing. Most research has focused on the influence of doorway width, and little is known about other doorway characteristics influencing doorway freezing. Firstly, to provide guidelines on how to design doorways for people with freezing. Secondly, to compare people with doorway freezing to people without doorway freezing, and to explore the underlying mechanisms of doorway freezing. We designed a web-based, structured survey consisting of two parts. Part I (n = 171 responders), open to people with Parkinson's disease with freezing in general, aimed to compare people with doorway freezing to people without doorway freezing. We explored underlying processes related to doorway freezing with the Gait-Specific Attention Profile (G-SAP), inquiring about conscious movement processes occurring during doorway passing. Part II (n = 60), open for people experiencing weekly doorway freezing episodes, inquired about the influence of specific doorway characteristics on freezing. People with doorway freezing (69% of Part I) had higher freezing severity, longer disease duration, and scored higher on all sub scores of the G-SAP (indicating heightened motor, attentional, and emotional thoughts when passing through doorways) than people without doorway freezing. The main categories provoking doorway freezing were: dimensions of the door and surroundings, clutter around the door, lighting conditions, and automatic doors. We provide recommendations on how to maximally avoid freezing in a practical setting. Furthermore, we suggest that doorways trigger freezing based on visuomotor, attentional, and emotional processes.

Nutritional status of pediatric patients with inflammatory bowel diseases is related to disease duration and clinical picture at diagnosis

This cross-sectional study presents the nutritional status of newly diagnosed pediatric patients with Crohn’s disease (CD) and ulcerative colitis (UC) and its association with the duration of the disease and selected clinical features. We analyzed the data of 41 pediatric patients with CD and 29 with UC (mean age: 13.1 y, range: 5.2–18.0 y) up to 3 mo. from diagnosis. Anthropometry included body weight, body height, body mass index (BMI), three skinfold thicknesses, mid-upper arm circumference and mid-upper arm muscle circumference adjusted for age and sex using national standards. Anthropometry was linked to the disease duration, location of the disease, symptoms, and blood test results. Both studied groups presented significantly lower BMI compared to the reference population, but only children with CD characterized with significantly worse nutritional status according to arm anthropometry. In CD, better nutritional status was associated mainly with longer disease duration and, to a lesser extent, with extraintestinal manifestations, perianal disease, and small intestinal lesions. In UC, anemia at diagnosis was associated with poor nutritional status. Our finding emphasizes the need for more attentive diagnostic care for pediatric patients who exhibit extraintestinal symptoms or perianal disease with no obvious signs of malnutrition, to avoid diagnostic delays.

Endoscopic Ultrasound-Guided Celiac Plexus Block Can Be a Useful Procedure for Pain Relief in Chronic Pancreatitis When Used Selectively

Abstract Background and Objectives: Endoscopic ultrasound (EUS)-guided celiac plexus block (CPB) for pain relief in chronic pancreatitis (CP) has wide variation in results as reported in the literature. The objective was to find out the efficacy of EUS-CPB in painful CP from our region where phenotype of CP is different from West and to find out factors favoring response to EUS-CPB. Methods and Results: Patients with known CP who underwent EUS-CPB were assessed for response to CPB. Response to EUS-CPB was recorded as more than 50% reduction in visual analogue scale (VAS) score for pain severity at 1 week, 4 weeks, 12 weeks and 24 weeks after procedure. Factors between responders and nonresponders were analyzed. Among 29 patients who underwent EUS-CPB during the study period, response was seen in 72.4% patients after the procedure. The mean time to response to EUS-CPB was 1.22 (± 0.43) days. Mean duration of response was 8 months (± 4.73). Short duration of painful CP (≤2 years) was seen in 15 patients (51.72%) and long duration (&gt;2 years) was seen in 14 (48.27%). Among responders (21/29), those patients who had short duration of disease had significantly lower median VAS score at 12 weeks, (1 versus 3, p-value= 0.026) and at 24 weeks, (1.5 versus 2.5, p-value= 0.049), as compared to those with longer duration of disease. Overall, 83.3% males responded as compared to 54.54% females (p = 0.04). Significant proportion of subjects who responded either stopped or used analgesics occasionally (p &lt; 0.0001). There was no statistically significant difference in response to EUS-CPB with respect to age, prior history of endoscopic retrograde cholangiopancreatography (ERCP), etiology of CP, prior history of surgery, or whether only EUS-CBP was done (p &gt; 0.05 for all). Conclusion: EUS-CPB can be effective when used in select group of painful CP patient who are not immediate candidates for surgery especially in early course of disease. It can be offered to patients with persistent pain despite optimum medical therapy. When effective, it can reduce need for analgesic medication at least in short to medium term.

Inflammatory and synaptic PET imaging in behavioural variant frontotemporal dementia caused by a repeat expansion in C9orf72 (C9orf72‐FTD)

AbstractBackgroundPathophysiological mechanisms associated with neurodegeneration include chronic neuroinflammation and synaptic dysfunction/loss. Radiotracer [11C]PBR28 is a marker of inflammation which binds to a translocator protein expressed by activated microglia. [11C]UCB‐J is a marker of synaptic density which binds to synaptic vesicle protein 2A. We evaluated both tracers as biomarkers of C9orf72‐FTD.MethodThree individuals with C9orf72‐FTD (mean age 62.7 years) underwent two PET scans between 3 and 13 months apart using [11C]PBR28 and [11C]UCB‐J. Dynamic PET data were acquired for 90 minutes following injection of each tracer. Arterial plasma input functions were generated from arterial blood samples. Participants also had volumetric MRI scans for each PET scan. Age‐matched controls from different cohorts underwent the same procedures (n = 5 for [11C]PBR28; n = 17 for [11C]UCB‐J).Regions of interest (ROIs) were defined on co‐registered T1‐weighted MR images using the CIC anatomical atlas. [11C]PBR28 BPND values were generated using a simplified reference tissue model with a cerebellar reference region. [11C]UCB‐J DVR‐1 values were generated using regional VT normalised to the VT in the centrum semiovale. ROI volumes were expressed as a percentage of total intracranial volume. W‐scores computed from each control cohort, using age and gender as covariates, illustrated the magnitude of differences between cases and controls. W‐scores &gt;1.65 were considered abnormal for [11C]PBR28 and ←1.65 for [11C]UCB‐J and MRI.Result[11C]PBR28 w‐scores indicated significant neuroinflammation in FTD but varied between cases. Differences in BPND were greater than in volume in frontal/temporal/cingulate cortices in the individual with the longest disease duration (DD) (16‐17 years). Inversely, in the individual with the shortest DD (1‐2 years), there were greater differences in volume than BPND in most ROIs.[11C]UCB‐J w‐scores indicated significant synaptic dysfunction/loss and were lower than w‐scores of volume in all cortical ROIs. In the individual with the longest DD, differences in [11C]PBR28 were greater than in [11C]UCB‐J in most ROIs. An inverse pattern again observed in the individual with the shortest DD suggests synaptic dysfunction/loss may precede significant neuroinflammation.ConclusionInflammatory and synaptic PET may provide more sensitive biomarkers of C9orf72‐FTD than MRI. Variability in PET signal within this genotype may be explained by DD.

NOTCH2NLC trinucleotide interruptions are associated with cognitive impairment in neuronal intranuclear inclusion disease (NIID)

AbstractBackgroundAbnormal GGC expansion within the NOTCH2HLC gene causes neuronal intranuclear inclusion disease (NIID), a rare neurodegenerative disease with variable clinical manifestations, including cognitive dysfunction. In addition to GGC repeats, there are two forms of repeated interruptions, GGA and AGC, within NOTCH2NLC repeats. Previous studies reported fewer GGA and more AGC interruptions in patients with Parkinson Disease; fewer GGA and AGC interruptions in patients with essential tremor, compared to NIID patients. These results suggest that trinucleotide interruptions within the NOTCH2NLC GGC repeats could influence the phenotype of disease, although the mechanism is not known.MethodsWe looked at the repeat compositions in NOTCH2NLC in NIID patients with and without cognitive impairment (CI). NOTCH2NLC repeats were screened by long‐read sequencing on the Oxford Nanopore platform.ResultsIn 13 NIID patients with NOTCH2NLC repeat expansion, 9 (69%) presented with CI. Patients with CI were older [mean (SD) = 69.7 (5.8) vs 63.3 (7.2)], had later age at onset [63.2 (6.5) vs 59.8 (7.1)] and longer disease duration [6.9 (5.2) vs 3.5 (3.9)] than patients without CI. The NOTCH2NLC repeats range from 89‐138 repeats in patients with CI; 82‐166 repeats in patients without CI. Patients with CI carried more GGC repeats [97.7 (1.7) vs 92.8 (9.0)] and less GGA [0.8 (1.3) vs 2.2 (2.8)] and AGC [0.6 (1.0) vs 3.5 (7.4)] interruptions within NOTCH2NLC, compared to patients without CI.ConclusionOur results suggest that NIID patients with cognitive impairment have a purer GGC repeat in NOTCH2NLC compared to patients without cognitive impairment, supporting previous studies that repeat interruptions may modify clinical manifestation of NIID.

Comparison of clinicopathologic features of Limbic and Diffuse Transactive Response DNA‐binding Protein 43 pathology in Alzheimer’s disease neuropathologic spectrum

AbstractBackgroundIncreasing evidence suggests that transactive response DNA‐binding protein 43 (TDP‐43) pathology in Alzheimer’s Disease (AD), or AD‐TDP, can be diffuse or limbic‐predominant. Understanding whether diffuse AD‐TDP has genetic, clinical, and pathological features that differ from limbic AD‐TDP could have clinical and research implications. We aimed to better characterize the clinicopathologic features of diffuse AD‐TDP and differentiate it from limbic‐predominant AD‐TDP pathology.MethodThree hundred sixty‐three participants were prospectively recruited and followed in the Mayo Clinic Study of Aging, Alzheimer’s Disease Research Center, and Neurodegenerative Research Group and died between May 1999 and August 2021. All underwent genetic, clinical, neuropsychologic, and neuropathologic evaluations. At postmortem evaluation, they showed Alzheimer’s disease neuropathologic changes and TDP‐43‐immunoreactive inclusions. The distribution of TDP‐43 pathology was assessed using the Josephs 6‐stage scheme. Participants with TDP‐43 stages 1‐3 were classified as Limbic, while those with stages 4‐6 were classified as Diffuse. Neuropathologically defined frontotemporal lobar degeneration cases were excluded. Multivariable logistic regression was used to identify clinicopathological features that predicted diffuse TDP‐43 pathology at postmortem. We hypothesized that the Diffuse group would show impairment in cognitive domains beyond episodic memory and more hippocampal sclerosis.ResultsThe cohort was 61% female and old at onset (median:76 years [IQR:70‐82]) and death (median:88 years [IQR:82‐92]). Fifty‐four percent (n = 197) were classified as Limbic and 46% (n = 166) as Diffuse. A “clinical” multivariate logistic regression fit to 85 participants with all clinical variables of interest showed that later age at onset (OR:1.09, 95%CI:1.01‐1.19;P = 0.03), longer disease duration (OR:1.17, 95%CI:1.02‐1.36;P = 0.03) and higher Neuropsychiatric Inventory scores (OR:1.14, 95%CI:1.01‐1.28;P = 0.03) all independently increased the odds of being Diffuse, while higher Trails Making Test‐B (OR:0.99, 95%CI:0.98‐0.99;P = 0.02) and Block Design Test scores (OR:0.91, 95%CI:0.85‐0.99;P = 0.023) independently decreased the odds of being Diffuse. A “pathology” multivariate logistic regression fit to 233 cases with all neuropathological data revealed that widespread amyloid‐β pathology corresponding to Thal phases 3‐5 all significantly decreased the odds of diffuse pathology by 80‐90%, while hippocampal sclerosis increased it sixfold (OR:6.18, 95% CI:2.93‐13.03;P&lt;0.001).ConclusionsDiffuse AD‐TDP shows clinicopathological features that differ from Limbic AD‐TDP, which could have public health implications relating to treatment and research on AD and dementia.

Mortality in patients with psoriatic arthritis in Sweden: a nationwide, population-based cohort study

ObjectivesTo compare all-cause mortality and causes of death between patients with psoriatic arthritis (PsA) and the general population in Sweden.MethodsAdults with at least one main PsA diagnosis (International Classification of...

Clinical and genetic risk factors for cystic fibrosis-related liver disease in Egyptian CF children: A single-center experience.

Cystic fibrosis (CF) is an autosomal recessive disease. It affects multiple organ systems, including the liver, leading to CF-related liver disease (CFLD). It was noted that CFLD in Egyptian children with CF is more common than in non-Egyptian people with CF (pwCF). This study aimed to determine the incidence of CFLD and the potential risk factors for developing CFLD in Egyptian children. The correlation between CFLD and the various genotypes prevalent in Egyptian CF children will be discussed. In addition, comparison of CFLD in Egyptian and non-Egyptian CF patients will be presented. This cross-sectional study included 50 pwCF from Ain Sham University's Pediatric Pulmonology Clinic in Children's Hospital, Cairo, Egypt. The sweat chloride test and genetic studies were done at the time of diagnosis. Additionally, all subjects underwent detailed history taking, laboratory investigations, clinical assessment, and pelvic abdominal ultrasound for evaluation of hepatic involvement. One-third of the Egyptian children with CF were found to have liver disease. The following independent risk factors for developing CFLD were identified as: male sex, severe genetic mutation (class I and II), long duration of CF disease, early onset of the CF, pancreatic insufficiency, as well as history of meconium ileus. In addition, diabetes mellitus and severe lung disease were proven to significantly increase the risk of developing CFLD. CFLD is common in Egyptian pwCF. CFLD's risk factors are similar to otherreported research from other countries in the region.

Awareness of Diabetic Retinopathy Among Patients With Type 2 Diabetes Mellitus in Primary Healthcare Centers in Madinah, Saudi Arabia: A Cross-Sectional Study.

Background The prevalence of diabetes mellitus (DM) in Saudi Arabia is among the highest in the Middle East and North Africa (MENA) regions. Various complications of DM can cause problems in the long term. One of the most prevalent microvascular problems and the primary cause of blindness is diabetic retinopathy (DR), and a significant proportion of the population with diabetes eventually develop diabetes retinopathy. Recognizing and understanding DR may be crucial for patients in identifying and averting this complication. Objectives The objective of this atudy is to assess the awareness of DR among patients with type 2 DM at primary healthcare centers in Madinah, Saudi Arabia. Methods This cross-sectional study involved a survey of patients with diabetes who attended Madinah primary care clinics between August and September 2023. The study was conducted in Madinah, Saudi Arabia, from May to November 2023. Results A total of 240 patients participated with a median age of 49.7 years and a gender distribution of 121 (50.4%) men.Overall, less than half of patients had a fair level of knowledge (47.1%) and a good level of knowledge (42.1%) about DR, whereas 10.8% had poor knowledge. Physicians were the primary source of information for patients, followed by the internet, family, and friends. Higher levels of education, diabetes that had been present for a longer period, and regular eye exams were associated with better understanding. This study emphasizes the importance of improving patient knowledge and awareness of DR. Conclusions We observed a high level of awareness of DR among participants. Furthermore, higher awareness was associated with longer disease duration and compliance with diabetes treatment.

Factors Influencing Glucose Response to Exercise Following Oral Glucose Load

PURPOSE: Exercise can reduce postprandial hyperglycemia by increasing contraction-mediated glucose uptake in skeletal muscles. However, postprandial exercise does not always have similar effects in all patients. This study aimed to analyze the factors influencing glucose response to exercise following oral glucose load.METHODS: We enrolled 169 adults with impaired glucose tolerance (IGT, n = 64) and type 2 diabetes (T2D, n = 105). We measured fingertip capillary blood glucose level at 30-minute intervals over 2-hour after the 75-g oral glucose ingestion. In addition, a single bout of moderate-intensity aerobic exercise was conducted at 30 minutes after 75-g oral glucose ingestion. We also measured glycated hemoglobin (HbA1c), insulin, insulin resistance (HOMA-IR), β-cell function (HOMA-β), physical activity level questionnaire and anthropometrics.RESULTS: There was a significant difference in glucose concentration between the IGT and T2D groups (&lt;i&gt;p&lt;/i&gt; &lt;.001). Additionally, we found that patients with short diabetes duration (≤1 year) had significantly more decrease in glucose concentration than long diabetes duration (≥10 years) (&lt;i&gt;p&lt;/i&gt; &lt;.001). A regression analysis showed that waist circumference, visceral fat area, fasting glucose, HbA1c, and HOMA-IR affected glucose response to exercise following oral glucose load in patients with T2D.CONCLUSIONS: Higher volumes of exercise following an oral glucose load may be necessary for individuals with Type 2 Diabetes (T2D) who have a longer disease duration, larger waist circumference, increased visceral fat area, higher HbA1c levels, and elevated HOMA-IR values in order to prevent hyperglycemia.

Progression to Myelofibrosis in Patients with Essential Thrombocythemia: A Real-World Analysis from the Prospective MOST Study

Background: Essential thrombocythemia (ET) is a myeloproliferative neoplasm (MPN) characterized by clonal blood cell proliferation, excessive platelet production, constitutional symptoms, and increased risk of vascular complications, as well as a risk of progression to myelofibrosis (MF). Previous prognostic studies of patients with ET have largely been based on retrospective analyses, and limited prospective data exist regarding disease progression. The prospective Myelofibrosis and Essential Thrombocythemia Observational Study (MOST) collected real-world data from patients with ET. This analysis evaluates disease progression in patients with ET enrolled in MOST. Methods: MOST (NCT02953704) enrolled patients with ET aged ≥60 years, or with a history of thromboembolic events, or who were receiving ET-directed therapy (excluding aspirin only). Baseline clinical characteristics data were collected as previously described (Yacoub A. CLML. 2021). For this analysis, progression from ET to MF was defined as meeting 1 or more of the following criteria during the study period: 1) Bone marrow biopsy with fibrosis grade ≥2 or pathologic diagnosis of MF; 2) death owing to MF/myelodysplastic syndrome/acute myeloid leukemia; 3) circulating blasts &amp;gt;1% and new/worsening splenomegaly (SPM); 4)new/worsening SPM and ≥2 of white blood cell (WBC) count &amp;gt;11×10 9/L, hemoglobin (Hb) &amp;lt;10 g/dL, and platelet count &amp;lt;100×10 9/L. Median (range) follow-up was 57.3 months (42-70). Results: Of the 1237 patients with ET enrolled in MOST; 53 (4.3%) met criteria for progression to MF. Among patients with progression, most had progressed due to fibrosis (criteria 1, 56.6%); 15.1%, 11.3%, and 28.3% of patients progressed due to criteria 2, 3, and 4, respectively. Notably, only 176 patients (14.2%) enrolled in the study had bone marrow data available. Comparison of the enrollment characteristics of patients with and without progression identified no differences in age at enrollment or diagnosis (Table 1). However, time from diagnosis to enrollment and from diagnosis to end of study were significantly longer in patients with progression than those without (median 7.9 vs 4.2 years, median 12.7 vs 9.0 years, respectively; both P=0.001). Of all enrolled patients with vs without progression tested for known driver mutations, a higher percentage with progression were JAK2-positive vs those without progression (80.6% [29/36] vs 69.7% [598/858]). At enrollment, the percentages of patients with vs without progression receiving ET-directed therapies were similar (94.3% vs 94.8%). Among patients with vs without progression, mean baseline Hb was significantly lower (12.5 g/dL vs 13.1 g/dL; P=0.026), mean WBC counts were significantly higher (10.4×10 9/L vs 7.4×10 9/L; P&amp;lt;0.001), and mean platelet counts were comparable (418.6×10 9/L vs 455.0×10 9/L; P=0.466). MPN-SAF TSS was similar for patients with vs without progression at baseline. Fewer patients with vs without progression had ≥1 thrombotic events (1.9% [1/53] vs 3.7% [44/1184]) during the study, whereas a higher percentage of patients had ≥1 hemorrhagic events (7.5% [4/53] vs 1.3% [15/1184]). Conclusions: This real-world analysis of data from MOST showed that 4.3% of patients with ET progressed to MF during the study period. Compared with patients without progression, patients with ET to MF progression had longer duration of disease, higher WBC count, and lower Hb at enrollment; symptom burden at enrollment was similar between the 2 groups. One limitation of this study is the lack of bone marrow data for the majority of patients, suggesting a possible underestimation of progression to MF. These findings and further analysis of MOST data will add insight into disease progression in patients with ET and facilitate clinical management of this patient population.

Fecal microbiota transplantation through transendoscopic enteral tubing for inflammatory bowel disease: High acceptance and high satisfaction.

Fecal microbiota transplantation (FMT) has been shown to positively affect the treatment of inflammatory bowel disease (IBD). However, the safety and efficacy of FMT may depend on the route of microbiota delivery. This study investigates the acceptance, satisfaction, and selection preference of a new delivery route, transendoscopic enteral tubing (TET), for treating IBD. A survey was conducted among patients with IBD from five medical centers across China. The objective was to assess their acceptance, subjective feelings, and major concerns regarding two types of TET: colonic TET and mid-gut TET. In addition, the survey also analyzed the factors affecting the selection of TET and TET types among these patients. The final analysis included 351 questionnaires. Up to 76.6% of patients were willing to accept TET and preferred to choose colonic TET when they first learned about TET. Patients with longer disease duration, history of enema therapy, or enteral nutrition were more open to considering TET among IBD patients. After treatment, 95.6% of patients were satisfied with TET, including colonic TET (95.9%) and mid-gut TET (95.1%). Patients with a history of enema therapy and ulcerative colitis preferred colonic TET. In contrast, those with a history of enteral nutrition and Crohn's disease were willing to choose mid-gut TET. However, some patients hesitated to accept TET due to concerns about efficacy, safety, and cost. TET was highly accepted and satisfied patients with IBD. Disease type and combination therapy influenced the choice of colonic or mid-gut TET.

Multiple Sclerosis Progression and Relapse Activity in Children

Although up to 20% of patients with multiple sclerosis (MS) experience onset before 18 years of age, it has been suggested that people with pediatric-onset MS (POMS) are protected against disability because of greater capacity for repair. To assess the incidence of and factors associated with progression independent of relapse activity (PIRA) and relapse-associated worsening (RAW) in POMS compared with typical adult-onset MS (AOMS) and late-onset MS (LOMS). This cohort study on prospectively acquired data from the Italian MS Register was performed from June 1, 2000, to September 30, 2021. At the time of data extraction, longitudinal data from 73 564 patients from 120 MS centers were available in the register. The main outcomes included age-related cumulative incidence and adjusted hazard ratios (HRs) for PIRA and RAW and associated factors. Clinical and magnetic resonance imaging features, time receiving disease-modifying therapy (DMT), and time to first DMT. After applying the inclusion and exclusion criteria, the study assessed 16 130 patients with MS (median [IQR] age at onset, 28.7 [22.8-36.2 years]; 68.3% female). Compared with AOMS and LOMS, patients with POMS had less disability, exhibited more active disease, and were exposed to DMT for a longer period. A first 48-week-confirmed PIRA occurred in 7176 patients (44.5%): 558 patients with POMS (40.4%), 6258 patients with AOMS (44.3%), and 360 patients with LOMS (56.8%) (P < .001). Factors associated with PIRA were older age at onset (AOMS vs POMS HR, 1.42; 95% CI, 1.30-1.55; LOMS vs POMS HR, 2.98; 95% CI, 2.60-3.41; P < .001), longer disease duration (HR, 1.04; 95% CI, 1.04-1.05; P < .001), and shorter DMT exposure (HR, 0.69; 95% CI, 0.64-0.74; P < .001). The incidence of PIRA was 1.3% at 20 years of age, but it rapidly increased approximately 7 times between 21 and 30 years of age (9.0%) and nearly doubled for each age decade from 40 to 70 years (21.6% at 40 years, 39.0% at 50 years, 61.0% at 60 years, and 78.7% at 70 years). The cumulative incidence of RAW events followed a similar trend from 20 to 60 years (0.5% at 20 years, 3.5% at 30 years, 7.8% at 40 years, 14.4% at 50 years, and 24.1% at 60 years); no further increase was found at 70 years (27.7%). Delayed DMT initiation was associated with higher risk of PIRA (HR, 1.16; 95% CI, 1.00-1.34; P = .04) and RAW (HR, 1.75; 95% CI, 1.28-2.39; P = .001). PIRA can occur at any age, and although pediatric onset is not fully protective against progression, this study's findings suggest that patients with pediatric onset are less likely to exhibit PIRA over a decade of follow-up. However, these data also reinforce the benefit for DMT initiation in patients with POMS, as treatment was associated with reduced occurrence of both PIRA and RAW regardless of age at onset.

Comorbid Inducible Urticaria Is Linked to Non-Autoimmune Chronic Spontaneous Urticaria: CURE Insights

Patients with chronic spontaneous urticaria (CSU) can have comorbid inducible urticaria (CIndU). How comorbid CIndU affects patients and their CSU is largely unclear. To compare patients with CSU with and without comorbid CIndUs for differences in demographic features, clinical characteristics, and laboratory markers. We analyzed 708 patients with CSU of our Urticaria Center of Reference and Excellence enrolled in CURE, the chronic urticaria registry. CURE data collected until October 2022 were used to compare patients with and without comorbid CIndU for their demographic characteristics, disease onset, activity, impact, and control, as well as concomitant allergic and autoimmune diseases and laboratory parameters associated with autoimmune CSU. Of 708 patients with CSU, 247 (35%) had comorbid CIndU. Compared with patients with standalone CSU, patients with CSU with comorbid CIndU were significantly younger, had earlier disease onset, longer disease duration, higher impact on quality of life, and a higher rate of concomitant allergic diseases. Moreover, patients with CSU with comorbid CIndU less often had features linked to autoimmune CSU such as angioedema, concomitant autoimmune diseases, eosinopenia, low levels of total IgE, and low total IgE combined with elevated anti-thyroid peroxidase IgG. Autoimmune CSU may be less common in patients with comorbid CIndU than without, and comorbid CIndU may point to autoallergic CSU.

The semicircular canal function is preserved with little impact on falls in patients with mild Parkinson's disease

IntroductionPostural instability is a cardinal symptom of Parkinson's disease (PD), which suggests the vestibular system may be affected in PD. This study aimed to determine whether vestibular dysfunction is associated with the risk of falls in PD. MethodsWe prospectively recruited patients with de-novo PD at a tertiary medical center between December 2019 and March 2023. During initial assessment, each patient was queried about falls within the preceding year. All patients underwent evaluation of video head-impulse tests (video-HITs), motion analysis, mini-mental state examination (MMSE), and Montreal Cognitive Assessment (MOCA). We determined whether head impulse gain of the vestibulo-ocular reflex (VOR) was associated with clinical severity of PD or risk of falls. ResultsOverall, 133 patients (mean age ± SD = 68 ± 10, 59 men) were recruited. The median Movement Disorder Society-Unified Parkinson's Disease Rating Scale motor part (MDS-UPDRS-III) was 23 (interquartile range = 16–31), and 81 patients (61 %) scored 2 or less on the Hoehn and Yahr scale. Fallers were older (p = 0.001), had longer disease duration (p = 0.001), slower gait velocity (p = 0.009), higher MDS-UPDRS-III (p < 0.001) and H&Y scale (p < 0.001), lower MMSE (p = 0.018) and MOCA scores (p = 0.001) than non-fallers. Multiple logistic regression showed that MDS-UPDRS-III had a positive association with falling (p = 0.004). Falling was not associated with VOR gain (p = 0.405). The VOR gain for each semicircular canal showed no correlation with the MDS-UPDRS-III or disease duration. ConclusionsThe semicircular canal function, as determined by video-HITs, is relatively spared and has little effect on the risk of falls in patients with mild-to-moderate PD.

The assessment of atlantoaxial joint involvement in patients with rheumatoid arthritis, results from an observational “real-life” study

Atlantoaxial joint is a possible affected site during rheumatoid arthritis (RA) and, in this work, we evaluated its occurrence and associated characteristics in a “real-life” cohort. By a medical records review study of RA patients longitudinally followed-up, the occurrence of severe atlantoaxial joint involvement was estimated (incidence proportion and incidence rate per 1000 person-years at risk). Regression analyses were also exploited to evaluate possible associated factors. Based on these findings, a prospective recruitment was performed to build a descriptive cross-sectional study in evaluating a subclinical atlantoaxial joint involvement in patients with the same clinical characteristics. Retrospectively, 717 patients (female 56.6%, age 64.7 ± 12.3 years) were studied. The incidence proportion of severe atlantoaxial joint involvement was 2.1% [1.5–2.5], occurring in 15 out of 717 patients, and identified by both MRI and CT scan. Considering over 3091 person-years, an incidence rate of 5.2 × 1000 [2.9–8.3] person-years was estimated. Regression analyses suggested that male gender, a longer disease duration, ACPA positivity and extra-articular manifestations resulted to be significantly associated with a severe atlantoaxial joint involvement. Given these findings, 30 asymptomatic patients were selected according to these clinical characteristics and underwent MRI of cervical spine. To date, almost 50% of these asymptomatic patients showed a subclinical atlantoaxial joint involvement. The occurrence of the severe atlantoaxial joint involvement in RA patients was estimated in a “real-life” setting. Male gender, ACPA positivity, long disease duration, and extra-articular manifestations could be associated with the severe atlantoaxial joint involvement in RA. MRI could provide a useful clinical tool to early evaluate the atlantoaxial joint involvement in RA, also in asymptomatic patients.