Similar Disease Research Articles

MRl and MRS hints for the differentiation of cerebellar multiple system atrophy from spinocerebellar ataxia type II

Background and objectivesThe differentiation of spinocerebellar ataxia type II (SCA 2) from idiopathic multiple systemic atrophy of the cerebellar type (MSA-C) is often difficult in patients with cerebellar ataxia when molecular testing is not available. Besides genetic testing, magnetic resonance imagining (MRI) and magnetic resonance spectroscopy (MRS) prove to be beneficial. Nevertheless, the characteristics observed through radiology change as the disease advances. Different radiological criteria may be needed across different stages of the disease. This study aimed to assess the radiological characteristics of MSA-C or SCA 2 patients across various stages of the disease and to identify potential distinguishing factors. MethodsBetween January 2000 and January 2020, a total of 390 patients, diagnosed with probable MSA-C according to the second consensus on MSA (317 cases) or with molecularly confirmed SCA 2 (73 cases), who had undergone at least one brain MRI and MRS targeting the cerebellar hemispheres, were enrolled in the study. The clinical parameters and neuroimaging features between these two diseases were compared and analyzed. ResultsA greater occurrence of a pontine hot cross bun sign (HCBS), higher scores on the scale for the assessment and rating of ataxia, and reduced levels of cerebellar N-acetyl aspartate (NAA)/creatine (Cr), and cerebellar choline (Cho)/Cr were found in MSA-C patients as compared with SCA 2 patients at similar disease durations. For the patients with an HCBS, a cerebellar Cho/Cr level of <0.53 was indicative of the potential presence of MSA-C, with significant level of specificity (85.96%). DiscussionDiscerning SCA2 from MSA-C using MRI and MRS appears to be plausible at various disease stages.

Post-hospitalization Short Versus Long Steroid Taper Strategies in Patients With Acute Severe Ulcerative Colitis: A Comparison of Clinical Outcomes.

Ulcerative colitis (UC) is a chronic inflammatory colon disease characterized by relapsing flares and remission episodes. However, the optimal steroid tapering strategy in patients hospitalized for acute severe UC (ASUC) remains relatively unknown. We aim to examine the clinical outcomes in patients hospitalized for ASUC regarding variable prednisone taper regimens upon discharge. We retrospectively reviewed all adult patients admitted to our facility with ASUC between 2000 and 2022. Patients were divided into 2 groups based on the duration of steroid taper on discharge (< 6 and > 6 weeks). Patients who had colectomy at index admission were excluded from the analysis. The primary outcome was rehospitalization for ASUC within 6 months of index admission. Secondary outcomes included the need for colectomy, worsening endoscopic disease extent and/or severity during the follow-up period (6 months), and a composite outcome as a surrogate of worsening disease (defined as a combination of all products above). Two-sample t-tests and Pearson's chi-square tests were used to compare the means of continuous and categorical variables, respectively. Multivariate logistic regression analysis was performed to identify independent predictors for rehospitalization with ASUC. A total of 215 patients (short steroid taper = 91 and long steroid taper = 124) were analyzed. A higher number of patients in the long steroid taper group had a longer disease duration since diagnosis and moderate-severe endoscopic disease activity (63.8 vs. 25.6 months, p < 0.0001, 46.8% vs. 23.1%, P = ≤ .05, respectively). Both groups had similar disease extent, prior biologic therapy, and the need for inpatient rescue therapy. At the 6-month follow-up, rates of rehospitalization with a flare of UC were comparable between the 2 groups (68.3% vs. 68.5%, P = .723). On univariate and multivariate logistic regression, escalation of steroid dose within four weeks of discharge (aOR 6.09, 95% CI: 1.82-20.3, P = .003) was noted to be the only independent predictor for rehospitalization with ASUC. This is the first study comparing clinical outcomes between post-discharge steroid tapering regimens in hospitalized patients for ASUC. Both examined steroid taper regimens upon discharge showed comparable clinical results. Hence, we suggest a short steroid taper as a standard post-hospitalization strategy in patients following ASUC encounters. It is likely to enhance patient tolerability and reduce steroid-related adverse effects without adversely affecting outcomes.

Hearing dysfunction heralds an increase in non-motor burden and a worse quality of life in Parkinson's disease: new insights from non-motor spectrum.

Sensorial non-motor symptoms (NMSs) in Parkinson's disease (PD) still lack appropriate investigation in clinical practice. This study aimed to assess if and to what extent auditory dysfunction is associated with other NMSs in PD and its impact on patient's quality of life (QoL). We selected patients with idiopathic PD, without other concomitant neurological diseases, dementia, or diagnosis of any audiological/vestibular disease. Demographic and clinical data were collected. Patients underwent otoscopic examination, audiological testing with pure tone audiometry (PTA) and distortion product otoacoustic emissions (DPOAEs) and completed Non-Motor Symptoms Scale (NMSS) and Parkinson's Disease Questionnaires-39 (PDQ-39). ANCOVA and partial correlation analysis have been used for statistical analysis. 60 patients were enrolled and completed PTA and DPOAEs. 32 patients with hearing impairment (HI), assessed by PTA, (hearing threshold ≥ 25dB) showed similar disease duration, motor impairment, and staging, compared to patients without HI, but higher scores both in NMSS and in PDQ-39, except for cardiovascular (CV), gastrointestinal (GI), urogenital (U) and sexual function (SF) of NMSS. In addition, DPOAEs showed a significant correlation with higher scores both in NMSS and PDQ-39, except for CV, SF, GI, U and perceptual problem subdomains of NMSS. This study demonstrated that PD patients with HI have a greater burden of NMS and lower related QoL and functioning. Our results highlight the importance to reconsider HI as a NMS, in parallel with the others. HI evaluation, even in asymptomatic patients, may reveal a wider pathology with a worse QoL.

Association between microsatellite status and characteristics and outcomes of early-onset compared to late-onset rectal cancer

BackgroundMicrosatellite instability (MSI) is an important prognosticator for colorectal cancer (CRC). The present study aimed to assess the impact of MSI status on the characteristics and outcomes of early-onset compared to late-onset rectal cancer.MethodsThis retrospective cohort study used data from the US National Cancer Database (2004–2019) to assess the baseline characteristics, treatment patterns, short-term outcomes, and overall survival (OS) of early-onset rectal adenocarcinoma affecting patients < 50 years compared to late-onset rectal adenocarcinoma according to the MSI status.ResultsThe present study included 48,407 patients (59.9% male) with rectal cancer, 17.3% of patients were < 50 years and 6.3% had MSI-H tumors. In the early-onset group, patients with MSI-H tumors had a lower mean age (41.5 vs 43 years, p < 0.001) and presented less often with stage IV disease (22.1% vs 17.7%, p = 0.03) and liver metastasis (9.1% vs 13.5%, p = 0.011) than patients with MSS tumors. In the late-onset group, patients with MSI-H and MSS tumors had similar demographics, disease stage, and metastatic pattern, yet MSI-H patients more often received neoadjuvant radiation therapy (58.9% vs 55.1%, p = 0.009) and neoadjuvant systemic therapy (40% vs 36.2%, p = 0.005). In both age groups, MSI-H tumors were associated with more pathologic T3-4 stage and were more likely mucinous and poorly differentiated carcinomas than MSS tumors. The median OS of MSI-H tumors was similar to MSS tumors (108.09 vs 102.31 months, p = 0.1), whether in the early-onset (139.5 vs 134.2 months, p = 0.821) or late-onset groups (106.1 vs 104.3 months, p = 0.236).ConclusionsIn both age groups, MSI-H rectal cancers were more often mucinous and poorly differentiated carcinomas and had pT3-4 stage more often than MSS cancers. MSI-H rectal cancers tend to present less often with distant metastases and nodal involvement than MSS cancers only in early-onset, but not in late-onset rectal cancers. The association between MSI status and survival was not notable in this study, whether in the early-onset or late-onset groups.

Feasibility of regional center telehealth visits utilizing a rural research network in people with Parkinson's disease.

Impaired motor and cognitive function can make travel cumbersome for People with Parkinson's disease (PwPD). Over 50% of PwPD cared for at the University of Arkansas for Medical Sciences (UAMS) Movement Disorders Clinic reside over 30 miles from Little Rock. Improving access to clinical care for PwPD is needed. To explore the feasibility of remote clinic-to-clinic telehealth research visits for evaluation of multi-modal function in PwPD. PwPD residing within 30 miles of a UAMS Regional health center were enrolled and clinic-to-clinic telehealth visits were performed. Motor and non-motor disease assessments were administered and quantified. Results were compared to participants who performed at-home telehealth visits using the same protocols during the height of the COVID pandemic. Compared to the at-home telehealth visit group (n = 50), the participants from regional centers (n = 13) had similar age and disease duration, but greater disease severity with higher total Unified Parkinson's disease rating scale scores (Z = -2.218, p = 0.027) and lower Montreal Cognitive Assessment scores (Z = -3.350, p < 0.001). Regional center participants had lower incomes (Pearson's chi = 21.3, p < 0.001), higher costs to attend visits (Pearson's chi = 16.1, p = 0.003), and lived in more socioeconomically disadvantaged neighborhoods (Z = -3.120, p = 0.002). Prior research participation was lower in the regional center group (Pearson's chi = 4.5, p = 0.034) but both groups indicated interest in future research participation. Regional center research visits in PwPD in medically underserved areas are feasible and could help improve access to care and research participation in these traditionally underrepresented populations.

Outcomes of a mandatory non-medical switch of infliximab to a biosimilar for inflammatory bowel disease in British Columbia, Canada.

Despite infliximab biosimilars becoming widely used in inflammatory bowel disease (IBD) patients, real-world non-medical switching is sparse. A biosimilar non-medical switch was launched in British Columbia in 2019, the first Canadian province to do so, from Remicade to an approved biosimilar (CT-P13 or SB2). This study aims to obtain real-world evidence evaluating the clinical outcomes of non-medical switching from Remicade to the infliximab biosimilars. This is a retrospective observational study of stable IBD patients from the IBD Centre of BC who underwent the non-medical infliximab switch. The primary outcome is treatment continuation at 12 ± 2 months post-switch. Secondary outcomes include frequency of loss of response, adverse events, and immunogenicity within the first 12 months post-switch. A control group of patients maintained on the originator served as a comparison. Patients in the biosimilar switch group (n = 264) and originator group (n = 99), show similar demographics and disease characteristics. There was no difference in infliximab continuation between the biosimilar group (94.9%) and the originator group (90.1%) (P = 0.18). Reasons for discontinuation of infliximab included loss of response (4.04% vs 4.91%), immunogenicity (1.01% vs 0.75%), or adverse effect (1.01% vs 2.3%) in the infliximab originator vs biosimilar switch group, respectively. Similarly, no differences in safety or efficacy were observed between patients switched to CT-P13 or SB2. Non-medical biosimilar switch of infliximab demonstrates similar clinical outcomes compared to originator molecule continuation for therapy of IBD. These data support the safety and efficacy of non-medical infliximab switching in IBD patients.

Comparing the efficacy of vedolizumab between males and females: a post-hoc analysis of GEMINI-1 and VARSITY.

Vedolizumab is a first-line treatment option for ulcerative colitis. There are differences in incidence of ulcerative colitis between males and females, but whether sex affects treatment outcomes is less clear. We examined sex-based differences in patients with ulcerative colitis initiated on vedolizumab from two major randomized controlled trials (RCTs). We conducted a post-hoc analysis on participants with ulcerative colitis from the VARSITY and GEMINI-1 RCTs who received vedolizumab. Outcomes of interest were rates of clinical improvement, clinical remission, and endoscopic improvement at weeks 6, 14, and 52 in male and female participants, as were differences in concentrations of trough vedolizumab and C-reactive protein; 1009 persons in GEMINI-1 and VARSITY trials were included. Male and female patients had similar disease characteristics aside from males being more likely to have Mayo 3 grade endoscopic severity at baseline (62.8 vs. 48.9%, P < 0.001). At week 6, females were more likely to have endoscopic improvement (47.4 vs. 35.2%, P = 0.001) and increased vedolizumab trough levels [34.0 (23.0-44.5) vs. 28.9 (19.0-34.6), P < 0.001]. The probability of achieving clinical remission (28.9 vs. 34.5%, P = 0.057) or endoscopic improvement (35.5 vs. 39.3%, P = 0.212) at week 52 was not different between males and females. Females with ulcerative colitis treated with vedolizumab appear more likely to achieve early endoscopic improvement than males, though longer-term outcomes demonstrated no difference. Further studies are required to better understand mechanisms through which sex or sex-associated factors could influence response to therapy in ulcerative colitis.

Abstract 1581: Colony-stimulating factor-1 receptor as a potential therapeutic target in pancreatic ductal adenocarcinoma

Abstract Background: Pancreatic ductal adenocarcinoma (PDAC) is associated with poor prognosis, rising incidence and suffers from limited existing treatment options. Currently, salient features of PDAC are being investigated that can potentially predict immunotherapy outcomes, to identify small patient populations that can benefit from such strategies. Preliminary studies show that colony-stimulating factor-1 receptor (CSF1R), a surface receptor tyrosine kinase that drives survival, function, proliferation and differentiation of several myeloid lineage cell types can be a potentially interesting target for combination immunotherapy. Methods: PDAC patients from the TCGA PanCancer Atlas were stratified into CSF1Rhi and CSF1Rlo cohorts and clinically relevant characteristics were compared between the two. The mRNA expression of CSF1R and immunological markers of interest were evaluated and Gene Set Enrichment Analysis (GSEA) was run on the two groups to analyze differential expression of gene sets. Results: mRNA expression z-scores were used to classify 129 patient samples in the TCGA PanCancer Atlas dataset into CSF1Rhi (z-score&amp;gt;1, n=20) and CSF1Rlo (z-score&amp;lt;0, n=109) cohorts. Both have similar disease staging, MSI MANTIS scores, tumor mutation burden, median diagnosis age, sex and race distribution. However, the CSF1Rhi cohort has a distinct, non-conventional PDAC driver gene mutation profile (genomic alteration frequencies in CSF1Rhi vs CSF1Rlo cohorts respectively: a) KRAS: 30% vs 73% b) CDKN2A: 15% vs 57% and c) SMAD4: 5% vs 42%) (p-value&amp;lt;0.01 for each). CSF1R correlates with markers of CD8+ T-cell function (R2 values: CD8A: 0.683, GZMB: 0.508, PRF1: 0.673), CD8+ T-cell infiltration (CXCL9: 0.596, CXCL10: 0.483, CCL5: 0.666) and expression of immune checkpoint genes (PDCD1: 0.602, CD274: 0.544, CTLA4: 0.613). CD8A, GZMB, PRF1, CXCL9, CXCL10, CCL5, PDCD1, CD274, CTLA4 are significantly upregulated in the CSF1Rhi group (log2Fold changes respectively: 2.07, 1.57, 1.48, 2.51, 1.71, 1.75, 1.63, 1.34, 1.80). GSEA against the hallmark gene set database shows that KRAS signaling, Inflammatory response, IL6 JAK STAT3 and Interferon-gamma signaling are significantly upregulated in the CSF1R high patient group (FDR q-value &amp;lt;0.01 for each). Conclusion: Preliminary in silico analysis suggests that PDAC patients with higher levels of CSF1R may be more immune infiltrated. Future studies will evaluate the potential of CSF1R as a biomarker to identify an immune infiltrated subset of PDAC patients ex vivo and the mechanism of immune infiltration in CSF1Rhi PDACs in vivo. Citation Format: Somak Chaudhuri, Dustin A. Deming, Cheri A. Pasch, Katherine A. Johnson, Chelsie K. Sievers, Philip B. Emmerich. Colony-stimulating factor-1 receptor as a potential therapeutic target in pancreatic ductal adenocarcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1581.

Biological treatment in elderly and young patients with ankylosing spondylitis: TURKBIO real-life data results.

This study aims to investigate the effect of age on disease activity and biological treatment in patients with ankylosing spondylitis (AS). A total of 811 AS patients registered in the TURKBIO registry database between 2011 and 2019 were categorized according to their age at the time of entry into the registry and assigned to one of two groups: young patients, defined as <60 years of age (n=610), and those aged ≥60 years (n=201) were recorded as elderly patients. Demographic, clinical, and laboratory characteristics, along with disease activity markers and other follow-up parameters, as well as current and prior treatments, were electronically recorded during each visit using open-source software. The mean age of the elderly patients was 67±5.8 years, while the mean age of the younger patients was 49.2±10.9 years. Male predominance was lower in the older AS group compared to the younger AS group (p=0.002). During follow-up period, 397 patients (comprising 318 young and 79 elderly individuals) had a history of using at least one biological disease-modifying agent (bDMARD). There was no significant difference between the groups in terms of DMARD and bDMARD-use distributions. First tumor necrosis factor inhibitor (TNFi) retention rates were found to be similar in both groups over 10 years of follow-up. Adverse events were found to be similar in young (19.9%) and elderly (26.8%) AS patients. Research in the TURKBIO cohort reveals that both older and younger patients with AS exhibited similar disease activity levels with comparable treatment approaches. Moreover, the results of TNFi treatments in elderly patients were the same as those observed in younger patients, with no notable increase in safety concerns.

Roflumilast Cream 0.3% in Patients With Chronic Plaque Psoriasis: Individual Patient PASI and PASI-HD Responses: Pooled DERMIS-1 and DERMIS-2 Phase 3 Trials

Background: Roflumilast cream 0.3% is a highly potent phosphodiesterase 4 inhibitor approved as a nonsteroidal, once-daily treatment for patients with plaque psoriasis. Pooled efficacy and safety results from two Phase 3 clinical trials (DERMIS-1 and DERMIS-2) have been presented previously. The Psoriasis Area and Severity Index (PASI) is used to assess the severity of plaque psoriasis in clinical trials; however, PASI is not precise when the area of involvement is &lt;10% of a given anatomic region. A modified version of the PASI, the PASI-high discrimination (PASI-HD), allows more precise assessment of psoriasis in body regions where &lt;10% area is affected. We present individual patient responses using PASI and PASI-HD.&#x0D; Methods: Patients aged ≥2 years with at least mild plaque psoriasis involving 2-20% body surface area were randomized 2:1 to apply roflumilast cream 0.3% or vehicle cream once daily for 8 weeks. The primary efficacy endpoint was Investigator Global Assessment (IGA) Success (score of Clear or Almost Clear plus ≥2-grade improvement from baseline) at Week 8. PASI and PASI-HD were used to measure disease severity; individual patient PASI and PASI-HD responses were plotted graphically. Safety and tolerability were also evaluated and were reported previously.&#x0D; Results: Roflumilast- and vehicle-treated patients had similar baseline demographic and disease characteristics. At Week 8, statistically significantly more roflumilast- than vehicle-treated patients achieved IGA Success (39.9% vs. 6.5%; P&lt;0.0001). Statistically significant differences favoring roflumilast were observed at Week 8 for percentages of patients achieving a 50% reduction in PASI (72.1% vs. 25.5%; P&lt;0.0001), 75% reduction (40.3% vs. 6.5%, P&lt;0.0001), 90% reduction (19.7% vs 2.3%; P&lt;0.0001), and 100% reduction (12.3% vs 0.8%; P&lt;0.001). Likewise, statistically significant differences favoring roflumilast were observed at Week 8 for percentages of patients achieving 50% reduction in PASI-HD (79.4% vs. 33.1%; P&lt;0.0001), 75% reduction (59.9% vs. 17.9%, P&lt;0.0001), 90% reduction (39.9% vs 9.1%; P&lt;0.0001), and 100% reduction (12.3% vs 0.8%; P&lt;0.0001). Roflumilast cream demonstrated low rates of application-site adverse events (AEs), treatment-related AEs, and discontinuations due to AEs, comparable to vehicle. At the first application of roflumilast cream 0.3% (day 1), 96% of patients reported no or mild sensation, increasing to 99% of patients at Weeks 4 and 8.&#x0D; Conclusions: Roflumilast cream 0.3% provided greater improvement in IGA Success, PASI, and PASI-HD versus vehicle with favorable safety and tolerability in patients with psoriasis in two Phase 3 trials. PASI-HD provided higher discrimination of effects of treatment in areas with &lt;10% involvement than the traditional PASI.&#x0D; ClinicalTrials.gov Identifiers: DERMIS-1: NCT04211363; DERMIS-2: NCT04211389&#x0D; Financial Disclosures: Arcutis Biotherapeutics, Inc.

Intensive Blood Pressure Lowering in Individuals With Low Diastolic Blood Pressure and Elevated Troponin Levels in SPRINT.

Among individuals with hypertension and low diastolic blood pressure (DBP), the optimal BP target remains controversial due to concerns that BP lowering may reduce coronary perfusion. We determined the impact of intensive BP control among individuals with elevated systolic BP who have low DBP and elevated hs-cTnT (high-sensitivity cardiac troponin T) levels. A total of 8828 participants in SPRINT (Systolic Blood Pressure Intervention Trial) were stratified by baseline DBP. Those with low DBP (<70 mm Hg) were further stratified by elevated hs-cTnT (≥14 ng/L) at baseline. The effects of intensive versus standard BP lowering on a cardiovascular disease composite end point, all-cause death, and 1-year change in hs-cTnT were determined. The combination of low DBP/high hs-cTnT was independently associated with a higher risk for cardiovascular disease and all-cause death, as well as greater 1-year increases in hs-cTnT, compared with DBP ≥70 mm Hg. However, randomization to intensive versus standard BP lowering led to similar reductions in cardiovascular disease risk among individuals with low DBP/high hs-cTnT (hazard ratio [HR], 0.82 [95% CI, 0.57-1.19]), low DBP/low hs-cTnT (HR, 0.48 [95% CI, 0.29-0.79]), and DBP ≥70 mm Hg (HR, 0.73 [95% CI, 0.60-0.89]; P for interaction=0.20). Intensive BP lowering also led to a reduction in all-cause death that was similar across groups (P for interaction=0.57). In this nonprespecified subgroup analysis of SPRINT, individuals with low DBP and elevated hs-cTnT, low DBP and nonelevated hs-cTnT, and DBP ≥70 mm Hg derived similar cardiovascular disease and mortality benefits from intensive BP lowering. These findings warrant confirmation in other studies.

Association Between Early Clinical Responses and Long-Term Outcomes With Ruxolitinib Cream Treatment in Mild to Moderate Atopic Dermatitis

In the TRuE-AD1/2 studies, patients aged ≥12 years with atopic dermatitis (Investigator’s Global Assessment [IGA] 2/3; 3%–20% affected body surface area) were randomized (2:2:1) to twice-daily 0.75%/1.5% ruxolitinib cream or vehicle for an 8-week, double-blind period followed by a 44-week long-term safety (LTS) period of as-needed ruxolitinib cream. This analysis examines associations between Week 8 responder status to 1.5% ruxolitinib cream with LTS outcomes. At Week 8, 57.0% (244/428) of LTS-evaluable patients applying 1.5% ruxolitinib cream achieved IGA–Treatment Success (IGA-TS; IGA 0/1 with ≥2-grade improvement from baseline); 66.6% (285/428) achieved ≥75% improvement in Eczema Area and Severity Index from baseline (EASI-75); 45.8% (196/428) achieved Itch numerical rating scale 0/1 (NRS 0/1). For patients with ≥2 visits (every 4 weeks) during LTS, mean percentages of visits with clear/almost clear skin were 83.2% vs 59.7%, 82.2% vs 54.9%, and 77.3% vs 70.1% for Week 8 IGA-TS, EASI-75, and Itch NRS 0/1 responders vs nonresponders, respectively. Mean percentages of visits with clear/almost clear skin were similar regardless of time to achieve IGA-TS (83.4%/77.4%/81.9% for those achieving at Week 2/4/8), EASI-75 (80.7%/78.8%/81.6%), and Itch NRS 0/1 (75.8%/70.7%/72.8%). During LTS, mean (SD) cumulative treatment-free days due to complete clearance were 149.2 (86.43) vs 104.0 (89.10), 146.4 (88.43) vs 95.9 (83.55), and 142.6 (87.58) vs 124.4 (91.47) for Week 8 IGA-TS, EASI-75, and Itch NRS 0/1 responders vs nonresponders, respectively. Percentage of treatment-free days between study visits (between Weeks 8 and 12 vs Weeks 48 and 52) among Week 8 responders and nonresponders increased from 44.1% to 50.2% and from 16.3% to 42.3% for IGA-TS; from 41.2% to 49.9% and from 14.9% to 40.6% for EASI-75; from 39.8% to 49.4% and from 29.9% to 46.0% for itch NRS 0/1. In summary, efficacy responses achieved with 8-week ruxolitinib cream treatment are associated with higher disease control in LTS; however, nonresponders approach similar disease control with continued treatment. As-needed ruxolitinib cream monotherapy demonstrated substantial long-term disease control regardless of time to first response achievement.

Impact of Covid -19 incidence rate and government-initiated risk communication measures on individual's NPI practices.

Non-pharmaceutical interventions (NPI) are the most widely recognized public health measures recognized globally to prevent the spread of Covid-19. NPIs' effectiveness may depend on the type, combination of applied interventions, and the level of proper public compliance with the NPIs. The expected outcome of behavioural practices varies relative to the intervention duration. This study aimed to assess the trend of community compliance to NPI with Covid-19 incidence and government-initiated interventions, and its variation by residence and sociodemographic characteristics of people. A weekly non-participatory field survey on individuals' NPI practices was observed from the 41st epidemiological week of October 5th, 2020, to the 26th epidemiological week of July 4th, 2021, a total of 39 weeks. The survey covered all 14 regional and national capital cities in Ethiopia. Data collection for the three NPI behaviours (i.e., respiratory hygiene, hand hygiene, and physical distance) was managed weekly at eight public service locations using the Open Data Kit (ODK) tool. The Covid- 19 incidence data and public health measures information from August 3rd, 2020 to July 4th, 2021 were obtained from the Ethiopian Public Health Institute (EPHI). More than 180,000 individuals were observed for their NPI practice, with an average of 5,000 observations in a week. About 43% of the observations were made in Addis Ababa, 56% were male and 75% were middle age group (18-50 years). The overall level of NPI compliance was high at the beginning of the observation then peaked around the 13th- 15th epidemiological weeks then declined during the rest of the weeks. The peak NPI compliance periods followed the high Covid-19 death incidence and government-initiated intensive public health measures weeks. Respiratory hygiene had the highest compliance above 41% whereas hand hygiene was the lowest (4%). There was a significant difference between residents of the capital city and regional cities in their level of compliance with NPI. Females comply more than males, and individuals had increased NPI compliance at the bank service and workplaces compared to those in the transport services at P = 0.000. An increased level of compliance with NPI was observed following intensive government-initiated Covid-19 prevention measures and an increased Covid-19 death incidence. Therefore, the intensity of government-initiated risk communication and public advocacy programs should be strengthened, possibly for similar respiratory disease pandemics in the future.

Pre-existing Immunocompromising Conditions and Outcomes of Acute COVID-19 Patients Admitted for Pediatric Intensive Care.

We aimed to determine if pre-existing immunocompromising conditions (ICCs) were associated with the presentation or outcome of patients with acute coronavirus disease 2019 (COVID-19) admitted for pediatric intensive care. Fifty-five hospitals in 30 US states reported cases through the Overcoming COVID-19 public health surveillance registry. Patients <21 years admitted 12 March 2020-30 December 2021 to the pediatric intensive care unit (PICU) or high-acuity unit for acute COVID-19 were included. Of 1274 patients, 105 (8.2%) had an ICC, including 33 (31.4%) hematologic malignancies, 24 (22.9%) primary immunodeficiencies and disorders of hematopoietic cells, 19 (18.1%) nonmalignant organ failure with solid-organ transplantation, 16 (15.2%) solid tumors, and 13 (12.4%) autoimmune disorders. Patients with ICCs were older, had more underlying renal conditions, and had lower white blood cell and platelet counts than those without ICCs, but had similar clinical disease severity upon admission. In-hospital mortality from COVID-19 was higher (11.4% vs 4.6%, P = .005) and hospitalization was longer (P = .01) in patients with ICCs. New major morbidities upon discharge were not different between those with and without ICC (10.5% vs 13.9%, P = .40). In patients with ICCs, bacterial coinfection was more common in those with life-threatening COVID-19. In this national case series of patients <21 years of age with acute COVID-19 admitted for intensive care, existence of a prior ICCs were associated with worse clinical outcomes. Reassuringly, most patients with ICCs hospitalized in the PICU for severe acute COVID-19 survived and were discharged home without new severe morbidities.

Quercetin improves epithelial regeneration from airway basal cells of COPD patients.

Airway basal cells (BC) from patients with chronic obstructive pulmonary disease (COPD) regenerate abnormal airway epithelium and this was associated with reduced expression of several genes involved in epithelial repair. Quercetin reduces airway epithelial remodeling and inflammation in COPD models, therefore we examined whether quercetin promotes normal epithelial regeneration from COPD BC by altering gene expression. COPD BC treated with DMSO or 1 µM quercetin for three days were cultured at air/liquid interface (ALI) for up to 4 weeks. BC from healthy donors cultured at ALI were used as controls. Polarization of cells was determined at 8 days of ALI. The cell types and IL-8 expression in differentiated cell cultures were quantified by flow cytometry and ELISA respectively. Microarray analysis was conducted on DMSO or 1 µM quercetin-treated COPD BC for 3 days to identify differentially regulated genes (DEG). Bronchial brushings obtained from COPD patients with similar age and disease status treated with either placebo (4 subjects) or 2000mg/day quercetin (7 subjects) for 6 months were used to confirm the effects of quercetin on gene expression. Compared to placebo-, quercetin-treated COPD BC showed significantly increased transepithelial resistance, more ciliated cells, fewer goblet cells, and lower IL-8. Quercetin upregulated genes associated with tissue and epithelial development and differentiation in COPD BC. COPD patients treated with quercetin, but not placebo showed increased expression of two developmental genes HOXB2 and ELF3, which were also increased in quercetin-treated COPD BC with FDR < 0.001. Active smokers showed increased mRNA expression of TGF-β (0.067) and IL-8 (22.0), which was reduced by 3.6 and 4.14 fold respectively after quercetin treatment. These results indicate that quercetin may improve airway epithelial regeneration by increasing the expression of genes involved in epithelial development/differentiation in COPD. This study was registered at ClinicalTrials.gov on 6-18-2019. The study number is NCT03989271.

Disease Course of Korean African Swine Fever Virus in Domestic Pigs Exposed Intraorally, Intranasally, Intramuscularly, and by Direct Contact with Infected Pigs.

African swine fever (ASF) is a fatal contagious disease affecting swine. The first Korean ASF virus (ASFV) isolate (Korea/Pig/Paju1/2019) was used to compare the disease course of ASFV in pigs inoculated via the four routes. In the challenge experiment, domestic pigs were infected via the intraoral (IO) and intranasal (IN) routes with a 106 50% hemadsorbing dose (HAD50) and an intramuscular (IM) injection of 103 HAD50. In the direct contact (DC) group, five naïve pigs were brought into direct contact with two IM-ASFV-infected pigs. IO-, IN-, and IM-inoculated pigs showed similar disease courses, whereas DC pigs had comparable ASF syndrome after a 7-day latent period. The disease course in the DC route, one of the most common routes of infection, was not significantly different from that in the IO and IN routes. IM and DC groups differed in terms of the severity of fever and hemorrhagic lesions in the lymph nodes and spleen, indicating that the IM route, suitable for early vaccine development trials, is not appropriate for studying the ASFV infection mechanism, including early stage of infection, and IO and IN challenges with a designated dose can be alternatives in trials for assessing ASFV pathogenicity and vaccine efficacy investigations.

Prevalence of Burn Pit Associated Symptoms Among US Veterans Who Utilize Non-Veteran's Affairs Private Healthcare.

Do the 3.5 million US veterans, who primarily utilize private healthcare, have similar burn pit exposure and disease compared to the VA Burn Pit registry? This is an online volunteer survey of Gulf War and Post-9/11 veterans. Burn pit exposure had significantly higher odds of extremity numbness, aching pain and burning, asthma, chronic obstructive pulmonary disease, interstitial lung disease, constrictive bronchiolitis, pleuritis, and pulmonary fibrosis. Chi-square did not reveal a difference in burn pit exposure and cancer diagnoses. These data demonstrate increased risk of neurological symptoms associated with burn pit exposure, which are not covered in the 2022 federal Promise to Address Comprehensive Toxics Act. Additional data will allow for the continued review and consideration for future medical benefits.

Resilience in patients and family caregivers living with congenital disorders of glycosylation (CDG): a quantitative study using the brief resilience coping scale (BRCS)

BackgroundPatients and family caregivers living with Congenital Disorders of Glycosylation (CDG) experience a heavy burden, which can impact their resiliency and quality of life. The study’s purpose was to measure the resilience levels of patients and family caregivers living with CDG using the brief resilience coping scale.MethodsWe conducted an observational, cross-sectional study with 23 patients and 151 family caregivers living with CDG. Descriptive analyses were performed to characterize patients with CDG and family caregivers’ samples. Additionally, we assessed correlations between resilience and specific variables (e.g., age, academic degree, time until diagnosis) and examined resilience differences between groups (e.g., sex, marital status, occupation, professional and social support).ResultsGNE myopathy was the most prevalent CDG among patients, while in family caregivers was PMM2-CDG. Both samples showed medium levels of resilience coping scores. Individuals with GNE myopathy had significantly higher scores of resilience compared to patients with other CDG. Resilience was positively correlated with educational degree in patients with CDG. Family caregivers had marginally significant higher scores of resilience coping if they received any kind of professional support or had contact with other families or people with the same or similar disease, compared with unsupported individuals.ConclusionsDespite the inherited difficulties of living with a life-threatening disease like CDG, patients and family caregivers showed medium resilient coping levels. Resilience scores changed significantly considering the CDG genotype, individual's academic degree and professional and social support. These exploratory findings can empower the healthcare system and private institutions by promoting the development of targeted interventions to enhance individuals` coping skills and improve the overall well-being and mental health of the CDG community.

Immune checkpoint inhibitors in high-grade upper tract urothelial carcinoma: Paradigm shift emphasizing organ preservation.

The aim was to evaluate the role of immune check point inhibitors (ICIs) in patients with high-grade upper tract urothelial carcinoma (UTUC) who are managed endoscopically when nephroureterectomy (NU) is not feasible, such as in patients who are either not candidates for NU or decline extirpative surgery. All patients diagnosed with high-grade UTUC and managed endoscopically between January 1996 and August 2022 were included in the study. Subsequently, patients were categorised based on their use of ICIs into group 1 (patients who did not receive ICIs) and group 2 (patients who received ICIs). Survival outcomes were assessed using Kaplan-Meier analysis, while a multivariable regression model was employed to analyse the impact of clinical characteristics on survival. A total of 29 patients were enrolled, with 14 in group 1 and 15 in group 2. Both groups exhibited similar demographic and disease characteristics, including multifocality, laterality and initial tumour size. The median follow-up period was 29.2months. Notably, group 2 demonstrated significantly enhanced overall and metastasis-free survival rates compared to group 1. At 47.8months, the overall survival rate was 0% (all patients died) in group 1, whereas it was 85.7% in group 2. Similarly, the metastasis-free survival rate was 0% (all patients had metastatic disease) in group 1 at 40.6months, whereas it reached 78.0% in group 2. The multivariable analysis indicated a correlation between ICI usage and improved survival outcomes, with a hazard ratio of 0.002. Utilisation of adjuvant ICIs in the setting of endoscopically treated patients with high-grade UTUC is associated with significantly improved survival rates. ICIs should be considered in this patient population, however, more studies with larger sample size are warranted.

88 Impacts of trace mineral source and ancillary drench on steer performance during a 60-day backgrounding phase

Abstract This experiment evaluated the impacts of supplementing organic complexed Cu, Co, Mn, and Zn on productive and health responses of high-risk beef cattle during a 60-d backgrounding phase. Crossbred steers (n = 120) were purchased at auction and transported to the experimental facility. Steer BW was recorded at arrival (d -1; initial shrunk BW = 227.7 ± 1.3 kg). On d 0, steers were ranked by BW and allocated to 1 of 8 groups (8 steers/group) and housed in drylot pens (6 m x 12 m) equipped with GrowSafe automated feeding systems (Model 8000; 2 bunks/pen; d 0 to 60). Groups were randomly assigned to receive a total mixed ration (TMR; 47% corn) containing: 1) sulfate sources of Cu, Co, Mn, and Zn (INR; n = 40); 2) organic complexed sources of Cu, Mn, Co, and Zn (AAC; Zinpro Availa 4; Zinpro Corp., Eden Prairie, MN; n = 40); or 3) AAC and an organic complexed trace mineral drench (APF; 30 mL/hd; Zinpro ProFusion, Zinpro Corp.) on d 0 and ancillary to morbidity treatment (n = 40). Diets provided the same daily amount of energy, protein, macro minerals and trace minerals based on 7 g/steer daily of Zinpro Availa 4. Steers were assessed for bovine respiratory disease (BRD) signs daily. Liver biopsies were performed on day 0, 28 and 60. Final BW was recorded on d 60 and 61. Blood samples were collected on d 0, 2, 6, 10, 13, 21, 28 and 45. No treatment differences were detected (P ≥ 0.23) for TMR intake, final BW, ADG, feed efficiency, or BRD incidence. Mean liver Co concentrations were greater (P = 0.02) in AAC and APF compared with INR steers. Mean liver Cu was greater (P = 0.02) in APF compared with AAC steers. Liver Zn tended to be greater (P = 0.10) on d 28 but less (P = 0.05) on d 60 for INR compared with AAC and APF steers. Plasma cortisol was least (P = 0.05) for steers supplemented with AAC on d 6, whereas AAC steers tended to have greater (P = 0.09) plasma cortisol on d 13 compared with APF. Plasma haptoglobin tended to be greater (P ≤ 0.10) for INR steers on d 28 and 45 compared with AAC and APF. While supplementing cattle with AAC or INR results in similar animal performance and clinical disease, AAC and APF reduces stress and acute phase protein responses.