Clinical Disease Research Articles

Impact of Seton Use on Clinical, Patient-Reported, and Healthcare Resource Utilization Outcomes in Complex Crohn’s Perianal Fistulas: A Systematic Literature Review

Abstract Background Optimal treatment strategies for seton use in patients with Crohn’s perianal fistulas (CPF) remain elusive. This systematic literature review aimed to summarize clinical, patient-reported, and healthcare resource utilization (HCRU) outcomes associated with seton use for symptomatic relief and treatment of complex CPF. Methods Electronic databases (MEDLINE, Embase, EBM Reviews, EconLit) were searched. Titles, abstracts, and relevant full texts were screened by 2 reviewers for inclusion using prespecified PICOS-T criteria. Articles published in English between January 1, 1980 and September 6, 2021 were included; animal/in vitro studies and case reports with <5 patients were excluded. Outcomes of interest included rates of complete response/remission and fistula recurrence in patients receiving seton with/without infliximab or biologics. Data were summarized using descriptive statistics. Results Overall, 56 studies were included (full texts: n = 43; congress abstracts: n = 13). CPF and clinical outcome definitions were heterogeneous. Rates (range) of complete response/remission varied widely (seton: 13%-75%; seton + infliximab: 23%-100%; seton + biologics: 23%-59%) as did rates for fistula recurrence (seton: 4%-68%; seton + infliximab: 0%-50%; seton + biologics: 0%-17%). Rates of fistula-related reintervention, new fistula or abscess formation, and abscess recurrence were also varied; more consistency was observed regarding the use of patient-reported outcomes. Few studies reported outcomes from pediatric/adolescent patients or HCRU. Conclusions Optimal use of seton in patients with CPF remains unclear. International standardization of definitions for CPF and related clinical outcomes are required to permit data comparability and identify the most effective treatment strategies involving seton use in CPF.

Musculoskeletal Injury in Australian Infantry Personnel: A Cross-sectional Study to Understand Prevention Priorities.

Musculoskeletal injury patterns are under-investigated in the Royal Australian Infantry Corps. Subsequently, more evidence is needed to support injury prevention processes in this population. One difficulty in collecting injury information to monitor injury patterns within combat populations accurately is known injury concealment behaviors in such populations. This study aims to examine musculoskeletal injury epidemiology within Australian infantry battalions using a tailored approach to mitigate reporting avoidance. A cross-sectional study using an anonymous online survey captured musculoskeletal injury information directly from personnel serving within 2 Australian infantry battalions. The survey requested information on participants' injury frequency in the previous 12 months and the context of participants' most severe injury. Injury context was restricted to the most severe during the period to limit recall bias. The applied injury case definition encompassed all injuries that affected an individual's ability to perform in their role. A descriptive analysis of all data recorded across the 2 battalions was conducted. Subgroup statistical difference was assessed by examining the 95% CI overlap between groups. The Department of Defence and Veterans' Affairs Human Research Ethics Committee granted ethical approval for this study. Overall, 166 individuals self-reported at least 1 injury in the past 12 months, representing a period prevalence of 55.5% (95% CI, 49.8-61.0%). No statistically significant prevalence differences existed between employment type, age, or sex. Approximately a quarter of injured participants were medically reclassified because of their injury, impacting their deployment fitness (n = 40, 24.4%). The following results relate to the most severe injury personnel experienced. Most injuries were service-related (n = 152, 91.6%). Field activities (n = 64, 39.3%) and physical training (n = 59, 36.2%) were the most common injury-related activities. Running was the most reported injury mechanism (n = 35, 21.7%), followed by pack marching (n = 29, 18.9%) and fall, slip, or trip (n = 18, 11.2%). Musculoskeletal injuries are common in the Australian infantry and significantly burden the workforce. Physical training and field exercises are most associated with injury and represent opportunities for injury risk-mitigation strategies to support the overall deployability of personnel and the combat effectiveness of their battalions. Future research should more formally explore the injury risk factors related to these activities using more robust study designs to collect injury and exposure information more accurately and reliably. One study strength includes using military-specific international injury surveillance guidelines to inform the survey design, to collect the recommended injury information for effective surveillance, and to enable future research comparison. A second study strength was tailoring the survey to promote participatory engagement, providing a high completion rate. A challenge in conducting this research was coordinating participant recruitment and data collection during domestic operations. Such challenges reflect the reality of conducting research in the military.

Preliminary evidence supporting use of UK consensus definitions for necrotising otitis externa

BackgroundInfections of the external ear canal (EAC) exist as a spectrum of disease from severe otitis externa (SOE) to necrotising otitis externa (NOE), but distinguishing between these is challenging. The UK consensus case definition (UKCCD) was established in 2022, but had not yet been assessed in clinical practice. MethodsAll consecutive adult patients undergoing CT to investigate a diagnosis of possible NOE between November 2018 and October 2019 were prospectively included in the cohort. Clinical diagnosis at baseline and the end of 12 months follow-up were compared to the diagnosis defined by UKCCD. Results55 patients were included in the analysis. 27 % (15/55) had an initial clinical diagnosis of NOE, of which 47 % (7/15) did not have changes on CT consistent with NOE. Only 9 % (5/55) patients had an MRI scan performed within 7 days of the baseline CT. At the end of 12 months, 9 % (5/55) patients had a change in diagnosis to or from NOE. All cases diagnosed as NOE by UKCCD had a clinical diagnosis of ‘NOE’ at baseline, while no cases clinically diagnosed as NOE were mislabelled by UKCCD as ‘not NOE’. All cases that had a change of diagnosis in the 12-month period or had an initial CT with no changes consistent with NOE, were captured by the UKCCD category of ‘possible NOE’. Median duration of antibiotics of clinically defined NOE cases were 14 days of intravenous (IQR: 7.3–23.8), 28 days of oral (IQR: 21.0–40.3), and 49.5 days combined (IQR: 29.8–67.3). ConclusionUKCCD has excellent clinical concordance with clinical diagnosis. Further work is warranted to assess its utility for risk stratification of patients presenting with severe infections of the EAC in a larger cohort.

Characterization of Neutrophil Functional Responses to SARS-CoV-2 Infection in a Translational Feline Model for COVID-19.

There is a complex interplay between viral infection and host innate immune response regarding disease severity and outcomes. Neutrophil hyperactivation, including excessive release of neutrophil extracellular traps (NETs), is linked to exacerbated disease in acute COVID-19, notably in hospitalized patients. Delineating protective versus detrimental neutrophil responses is essential to developing targeted COVID-19 therapies and relies on high-quality translational animal models. In this study, we utilize a previously established feline model for COVID-19 to investigate neutrophil dysfunction in which experimentally infected cats develop clinical disease that mimics acute COVID-19. Specific pathogen-free cats were inoculated with SARS-CoV-2 (B.1.617.2; Delta variant) (n = 24) or vehicle (n = 6). Plasma, bronchoalveolar lavage fluid, and lung tissues were collected at various time points over 12 days post-inoculation. Systematic and temporal evaluation of the kinetics of neutrophil activation was conducted by measuring markers of activation including myeloperoxidase (MPO), neutrophil elastase (NE), and citrullinated histone H3 (citH3) in SARS-CoV-2-infected cats at 4 and 12 days post-inoculation (dpi) and compared to vehicle-inoculated controls. Cytokine profiling supported elevated innate inflammatory responses with specific upregulation of neutrophil activation and NET formation-related markers, namely IL-8, IL-18, CXCL1, and SDF-1, in infected cats. An increase in MPO-DNA complexes and cell-free dsDNA in infected cats compared to vehicle-inoculated was noted and supported by histopathologic severity in respiratory tissues. Immunofluorescence analyses further supported correlation of NET markers with tissue damage, especially 4 dpi. Differential gene expression analyses indicated an upregulation of genes associated with innate immune and neutrophil activation pathways. Transcripts involved in activation and NETosis pathways were upregulated by 4 dpi and downregulated by 12 dpi, suggesting peak activation of neutrophils and NET-associated markers in the early acute stages of infection. Correlation analyses conducted between NET-specific markers and clinical scores as well as histopathologic scores support association between neutrophil activation and disease severity during SARS-CoV-2 infection in this model. Overall, this study emphasizes the effect of neutrophil activation and NET release in SARS-CoV-2 infection in a feline model, prompting further investigation into therapeutic strategies aimed at mitigating excessive innate inflammatory responses in COVID-19.

Deciphering Developmental Epileptic Encephalopathies (DEE): Unravelling the Key Signs

<p><strong>Background:</strong> Epilepsy, a chronic neurological disorder affecting over 50 million people worldwide, is marked by recurrent seizures and loss of consciousness. It is categorized based on EEG features, etiologies, and comorbidities. Developmental Encephalopathy (DE) involves developmental delays and early-onset seizures without causing developmental regression. In contrast, Epileptic Encephalopathy (EE) features severe epilepsy syndromes where frequent seizures result in developmental delays or regression.</p><p><strong>Methods:</strong> This review explores the clinical definitions, epidemiology, and diagnostic criteria for DE, EE, and DEEs. It covers their etiologies, clinical features, diagnostic methods, and treatment strategies, including genetic, structural, metabolic, and immune-related factors.</p><p><strong>Results:</strong> DE features developmental impairment with epilepsy, while EE involves severe epilepsy causing cognitive and behavioral dysfunction. DEEs are marked by early-onset severe epilepsy and EEG abnormalities that worsen developmental impairments. Essential diagnostic tools include EEG, neuroimaging, and genetic testing. Effective management requires personalized interventions to control seizures and address cognitive deficits.</p><p><strong>Conclusion:</strong> DEEs are a complex epilepsy subset with major developmental and cognitive challenges. Early diagnosis and targeted treatments are crucial for improving outcomes. Ongoing research into DEEs' genetic and pathophysiological mechanisms is key to enhancing understanding and management.</p>

Preventive DAN- Using Deep Learning for Early Detection

Diabetes is a global health issue often linked with diabetic neuropathy, specifically diabetic autonomic neuropathy (DAN), which affects the autonomic nerve system, potentially impacting vital organs. DAN is underdiagnosed due to financial constraints, limited access to diagnostic tools, challenges in assessments,and asymptomatic stages. This research tackles these issues by using electronic health records (EHRS) and deep learning to detect DAN, Machine learning algorithms overcome traditional diagnostic barriers, achieving 85.5% accuracy with a Random Forest (RF) model. A deep learning approach using the (LSTM) model outperforms traditional methods, reaching 95.7% accuracy. This study advances healthcare technology by demonstrating the effectiveness of AI, particularly deep learning, in detecting DAN accurately and efficiently. It highlights the potential of EHRS in improving clinical diagnosis support, complication detection, and disease monitoring in diabetic patients. Key Words: Diabetic Autonomic Neuropathy (DAN), Electronic Health Records (EHRs), Long Short-Term Memory (LSTM), Clinical Diagnosis, Early Detection, Cardiac Autonomic Neuropathy (DCAN).

Longitudinal objective assessment of speech in Multiple Sclerosis

BackgroundRemote objective tests may supplement in-clinic examination to better inform treatment decisions. Previous cross-sectional studies presented objective speech metrics as potential markers of Multiple Sclerosis (MS) disease progression. ObjectiveTo examine the short-term stability and long-term sensitivity of speech metrics to MS progression. MethodsWe prospectively recorded speech from people with MS at baseline, six, twelve weeks, and at ten months or longer after baseline (1y+). Only people with a definite diagnosis of MS and without other potential causes of dysarthria were included. Speech tasks comprehended 1) a sustained vowel /a/, 2) saying the days of the week, 3) repeating the non-word pa-ta-ka multiple times as fast as possible, 4) reading the Grandfather Passage, and 5) telling a personal story. We selected speech metrics of interest according to their association with MS presence, correlation with general disability, and short-term metric stability in the absence of disease progression. Selected speech metrics were analysed for short- versus long-term changes in the whole MS cohort and in the clinically stable versus progression subgroups at 1y+. ResultsSixty-nine people with MS participated (76.8 % female, age mean 47.5 ± 11.1 SD, EDSS median 3.5, interquartile range 3.5). Twenty-six unique speech metrics satisfied the suitability criteria. On average, reading rate improved 3.5 % for all people with MS and 6.5 % for slow readers with MS from baseline to the six-week, driven by a reduction in pauses. At 1y+, participants showed a 3.1 % average reduction in vocalization time during the reading task, which was similar in the progression (n = 29) and non-progression (n = 40) groups and thus unrelated to disease progression. Both findings are in the opposite direction of what would be generally expected for deterioration in speech performance and might be attributable to familiarity and training effects. Other speech metrics showed either negligible change or a similar variability between short-term and long-term differences. ConclusionMost individual long-term changes were small and within short-term variability intervals, irrespective of clinical disease progression. Familiarity and practice effects might have blunted the measurement of change. The present lack of longitudinal sensitivity of speech in MS contradicts previous cross-sectional findings and requires further investigation.

Epidemiology and genetic characterization of influenza viruses circulating in Bhutan in 2022.

Influenza (Flu) causes considerable morbidity and mortality globally, and in Bhutan, Flu viruses are a leading cause of acute respiratory infection and cause outbreaks during Flu seasons. In this study, we aim to analyze the epidemiology and the genetic characterization of Flu viruses circulated in Bhutan in 2022. Respiratory specimens were collected from patients who meet the case definition for influenza-like illness (ILI) and severe acute respiratory infection (SARI) from sentinel sites. Specimens were tested for Flu and SARS-CoV-2 viruses by RT-PCR using the Multiplex Assay. Selected positive specimens were utilized for Flu viral genome sequencing by next-generation sequencing. Descriptive analysis was performed on patient demographics to see the proportion of Flu-associated ILI and SARI. All data were analyzed using Epi Info7 and QGIS 3.16 software. A weekly average of 16.2 ILI cases per 1000 outpatient visits and 18 SARI cases per 1000 admitted cases were reported in 2022. The median age among ILI was 12 years (IQR: 5-28) and SARI was 6.2 (IQR: 2.5-15) years. Flu A(H3N2) (70.2%) subtype was the most predominant circulating strain. Flu A(H1N1)pdm09 and Flu B viruses belonged to subclades that were mismatched to the vaccine strains recommended for the 2021-2022 season but matched the vaccine strain for the 2022-2023 season with vaccine efficacy 85.14% and 88.07% respectively. Flu A(H3N2) virus belonged to two subclades which differed from the vaccine strains recommended in both the 2021-2022 and 2022-2023 seasons with vaccine efficacy 68.28%. Flu virus positivity rates were substantially elevated during the Flu season in 2022 compared to 2021. Flu A(H3N2) subtype was the most predominant circulating strain in the country and globally. Genetic characterization of the Flu viruses in Bhutan showed a close relatedness of high vaccine efficacy with the vaccine strain that WHO recommended for the 2022-23 season.

Neuropsychiatric symptoms in cognitive decline and Alzheimer’s disease: biomarker discovery using plasma proteomics

Background and objectivesNeuropsychiatric symptoms (NPS) are common in older people with cognitive impairment and Alzheimer’s disease (AD). No biomarkers to detect the related pathology or predict the clinical evolution of...

The Protective Effect of Astragalus Polysaccharide on Experimental Autoimmune Encephalomyelitis in Mice by Activating the AMPK/JAK/STAT3/Arginase-1 Signaling Pathway.

This study aimed to investigate the protective effect and mechanism of Astragalus polysaccharide (APS) on autoimmune encephalomyelitis. C57BL/6 mice were randomly divided into the blank control group, EAE group, and APS intervention group (n=15/group). The Experimental Autoimmune Encephalomyelitis (EAE) mouse model was established by active immunization. The pathological changes in the spinal cord were evaluated by Hematoxylin-eosin (HE) and Luxol Fast Blue (LFB) staining. The number of CD11b+ Gr-1+ myeloid-derived suppressor cells (MDSCs) in the spleen tissues of mice in each group was determined by immunofluorescence staining. The expression of Arginase-1 in the spinal cord and spleen of each group was detected by immunofluorescence double staining. The TNF-α, IL-6, and Arginase-1 levels in the spleen were detected by ELISA assay. A western blot was used to detect the protein expression of the AMPK/JAK/STAT3/Arginase-1 signaling pathway. After the intervention of APS, the incidence of autoimmune encephalomyelitis in mice of the APS group was significantly lower than that in the EAE group, and the intervention of APS could significantly delay the onset time in the EAE mice, and the score of neurological function deficit in mice was significantly lower than that in EAE group (P < 0.05). APS intervention could reduce myelin loss and improve the inflammatory response of EAE mice. Moreover, it could induce the expression of CD11b+ GR-1 + bone MDSCs in the spleen and increase the expression of Arginase-1 in the spinal cord and spleen. This study further demonstrated that APS can protect EAE mice by activating the AMPK/JAK/STAT3/Arginase-1 signaling pathway. After the intervention of APS, myelin loss and inflammatory response of EAE mice were effectively controlled. APS promoted the secretion of Arginase-1 by activating MDSCs and inhibited CD4+T cells by activating AMPK/JAK/STAT3/Arginase-1 signaling pathway, thus improving the clinical symptoms and disease progression of EAE mice.

Prevalence of symptoms of post-COVID-19 condition (long COVID) in children hospitalized with COVID-19: A systematic review of observational studies.

This systematic review aimed to investigate the prevalence of symptoms of post-COVID-19 condition (long COVID), in children hospitalized with COVID-19. We searched PUBMED and EMBASE on 15 March, 2023, using search strategy: "long COVID" OR "post-COVID-19" OR "postacute COVID-19" OR "long-term COVID" OR "COVID-19 sequelae" OR "persistent COVID-19" OR "chronic COVID-19". We included observational studies (case-control, cross-sectional, cohort, or case series) that investigated symptoms of post-COVID-19 condition (long COVID) in children (<18 years) admitted with COVID-19. We used the WHO case definition of post-COVID-19 condition. Long COVID was defined as persistence of otherwise unexplained symptoms for at least three months after SARS-CoV-2 infection. We used the command "metaprop" to perform random-effects meta-analysis. Eleven studies involving 2279 patients were included. In the period between ≥3 months and <12 months after acute COVID-19, the most frequent symptom was exercise intolerance with a pooled prevalence of 29% (95% CI: 7%-57%, I2 = 95%), followed by nonspecific respiratory symptoms (12%, 95% CI: 0%-48%, I2 = 0%), psychological disorders (10%, 95% CI: 1%-25%, I2 = 97%), and nonspecific gastrointestinal symptoms (10%, 95% CI: 0%-37%, I2 = 99%). In the period ≥12 months after the initial infection, the pooled prevalence of post COVID symptoms was lower, with 6% (95% CI: 2%-10%, I2 = 83%) for exercise intolerance and 3% (95% CI: 0%-8%, I2 = 89%) for fatigue. In conclusion, symptoms of post-COVID condition (long COVID) in hospitalized children affect multiple organ systems, with higher prevalence in the period up to 12 months after the acute phase of COVID-19.

Real-world Effectiveness of Sarilumab in RA: Results from the Open-label, Prospective, Single-arm Observational PROFILE Study.

The 1-year PROspective sarilumab (preFILled syringe/pen) multinational, obsErvational (PROFILE) study evaluated the real-world effectiveness and safety of sarilumab in patients with moderate-to-severe rheumatoid arthritis (RA). Safety endpoints included adverse events (AEs) and lab abnormalities. Effectiveness endpoints included the ACR core set. The primary endpoint was the change from baseline in Clinical Disease Activity Index (CDAI). All statistics are descriptive and pvalues were nominal. In total, 595 patients were treated, of whom 223 (37.5%) received sarilumab monotherapy and 372 (62.5%) received combination therapy. Upon initiation of sarilumab, an improvement in the mean (SD) CDAI score was observed at week 24 [11.4 (10.3)] and was maintained through week 52 [10.0 (10.5)], resulting in a mean [SD] reduction of -14.9 (12.7) and -14.4 (12.9), respectively. There were consistent improvements in disease activity that were similar for patients on monotherapy vs. combination therapy. An increase in the proportion of patients achieving remission and low disease activity was reported. By week 52, both groups had improved physical function and quality of life. There were no new safety signals. The proportions of any patients reporting a treatment-emergent adverse event (TEAE) or serious treatment-emergent AE (SAE) was 66.2% and 5.9%, respectively, and were similar between both treatment groups. Overall, 15.6% of patients discontinued sarilumab treatment due to TEAEs. The most commonly reported TEAE of interest was neutropenia (14.1%). In this 1-year, observational real-world study, sarilumab therapy resulted in improved clinical outcomes. The safety profile was consistent with that observed in sarilumab randomized clinical trials. This study was entered on the German website (Paul Ehrlich Institute) on January 11, 2018, with NIS No.: 423.

Incidence of Clinically Diagnosed Psoriatic Arthritis in Sweden.

Prior incidence estimates of psoriatic arthritis (PsA) vary considerably. We aimed to assess the annual incidence of clinically diagnosed PsA among adults in Sweden in 2014-2016, overall and stratified by age/sex/education/geography, and to investigate potential time trends in incidence in 2006-2018. Use of disease-modifying antirheumatic drugs (DMARDs) during the 2 years after diagnosis was also examined. Patients (aged ≥ 18 years) with incident clinically diagnosed PsA in Sweden were identified from the National Patient Register (NPR) and/or the Swedish Rheumatology Quality Register (SRQ). Population statistics, stratification variables, and DMARD information were retrieved from other nationwide registers. Incidence was estimated according to a base case (BC) definition (ie, ≥ 1 main International Classification of Diseases, 10th revision, diagnosis of PsA [L40.5/M07.0-M07.3] from rheumatology/internal medicine in NPR, or a PsA diagnosis in SRQ during the relevant year, and no prior such diagnoses) and 4 different sensitivity analysis case definitions. The mean annual incidence of clinically diagnosed PsA among adults in Sweden in 2014-2016 was estimated at 21.77 per 100,000 person-years (PYs) at risk, according to the BC definition; 17.41 per 100,000 PYs at risk after accounting for diagnostic misclassification; and 15.78 to 28.83 per 100,000 PYs at risk across all sensitivity analyses. Incidence was slightly higher in female individuals, was lower in those with higher education (aged > 12 years), and peaked during the ages of 50 to 59 years. No apparent increasing or decreasing time trend was observed in 2006-2018. Within 2 years of diagnosis, 71.03% of patients had received DMARD therapy (22.37% biologic or targeted synthetic DMARDs). From 2014 to 2016, the annual incidence of clinically diagnosed PsA in the adult Swedish population was approximately 20 per 100,000 PYs at risk. Two years after diagnosis, almost three-quarters of patients had received DMARD therapy.

A Real-World Analysis of Weather Variation on Disease Activity and Patient-Reported Outcomes in Psoriatic Arthritis.

Patients with inflammatory articular diseases, such as psoriatic arthritis (PsA), report weather changes in their symptoms. Our objective was to investigate the correlation between weather variation, disease activity (DA), and patient-reported outcomes (PROs) in patients with PsA. Hourly measurements of temperature, relative humidity, and pressure were obtained from 2015 to 2020 in Montreal (through Environment Canada) and were matched with DA and PROs of patients with PsA enrolled in Rhumadata. The differences in mean DA and PROs were examined between winter and summer. Pearson correlation coefficients were calculated between clinical profile and weather measurements. Among patients with PsA, 2665 PROs were collected for a total of 858 patients. The Clinical Disease Activity Index (P = 0.001) and Simplified Disease Activity Index (P < 0.001) were lower in winter. In summer, positive correlations were found between humidity and symptoms (using patient global assessment, fatigue, pain, C-reactive protein, Bath Ankylosing Spondylitis Disease Activity Index, Bath Ankylosing Spondylitis Functional Index), whereas negative correlations between temperature and Health Assessment Questionnaire-Disability Index were reported. In winter, positive correlations were observed between temperature, fatigue, and pain. This is the first study to investigate weather variations through subjective and objective PROs matched with patients with PsA. Statistically significant differences in clinical profile were evident between winter and summer, as well as in their correlation with weather measurements. However, these distinctions lack clinical significance, suggesting a small impact on patients with PsA.

Shotgun Analysis of Gut Microbiota with Body Composition and Lipid Characteristics in Crohn's Disease.

Alterations to intestinal microbiota are assumed to occur in the pathogenesis of inflammatory bowel disease (IBD). This study aims to analyze the association of fecal microbiota composition, body composition, and lipid characteristics in patients with Crohn's disease (CD). In our cross-sectional study, patients with CD were enrolled and blood and fecal samples were collected. Clinical and endoscopic disease activity and body composition were assessed and laboratory tests were made. Fecal bacterial composition was analyzed using the shotgun method. Microbiota alterations based on obesity, lipid parameters, and disease characteristics were analyzed. In this study, 27 patients with CD were analyzed, of which 37.0% were obese based on visceral fat area (VFA). Beta diversities were higher in non-obese patients (p < 0.001), but relative abundances did not differ. C. innocuum had a higher abundance at a high cholesterol level than Bacillota (p = 0.001, p = 0.0034). Adlercreutzia, B. longum, and Blautia alterations were correlated with triglyceride levels. Higher Clostridia (p = 0.009) and B. schinkii (p = 0.032) and lower Lactobacillus (p = 0.035) were connected to high VFA. Disease activity was coupled with dysbiotic elements. Microbiota alterations in obesity highlight the importance of gut microbiota in diseases with a similar inflammatory background and project therapeutic options.

Late Cancer Presentation and Increase Palliative Care Burden on Healthcare Delivery in Makurdi Benue State: A Need for Strategic Intervention

The study employed a narrative review design for the purpose of identifying statistical findings on late-stage cancer diagnosis from previously published studies to use as evidence to describe the prevailing incidence of patients’ presenting with late-stage cancer disease in Benue State. The data were searched from journals indexed in Google scholar, Semantic scholar, ResearchGate, Cross-references, PubMed, DOAJ, and Abstract journals. The statistical results obtained from the review shows that, late-stage cancer presentation among people who develop the disease is a common situation in Nigeria. Specifically, to Benue State one among the few published studies reported that patients who had presented with advanced clinical diseases as evidenced by fungating masses, palpable axillary nodes, are indications of histologically established metastatic disease. Another study applying the FIGO Staging method revealed that (81.8%) presented with advanced stage disease ranging from stage IIb–IV and stage III disease was the commonest with (42.9%) of cases. A recent study revealed that (46.7%) of patients were diagnosed with stage II disease. Whereas (49.1%) presented with advanced stage III and (1.3%) stage IV disease respectively. Based on these evidences, is the pertinent need to solicit for a strategic intervention by various stakeholders in the health system to establish a specialized palliative care service facility in Benue State. Late cancer presentation is an eligible condition for palliative care; early and routine referral of cancer patients for palliative care will accord patients the benefits of enjoying improved QOL and delay of early death from the disease.

The Effects of Vaccination Status and Age on Clinical Characteristics and Severity of Measles Cases in the United States in the Post-Elimination Era, 2001-2022.

Despite high vaccine-effectiveness, wild-type measles can occur in previously vaccinated persons. We compared the clinical presentation and disease severity of measles by vaccination status and age in the post-elimination era in the United States. We included U.S. measles cases reported from 2001-2022. Breakthrough measles was defined as cases with ≥1 documented dose of measles-containing vaccine, classic measles as the presence of rash, fever, and ≥1 symptoms (cough, coryza, or conjunctivitis), and severe disease as the presence of pneumonia, encephalitis, hospitalization, or death. Vaccinated cases with low and high avidity IgG were classified as primary (PVF) and secondary (SVF) vaccine failures, respectively. Among 4,056 confirmed measles cases, 2,799 (69%) were unvaccinated, 475 (12%) were breakthrough infections, and 782 (19%) had unknown vaccination; 1,526 (38%), 1,174 (29%), and 1,355 (33%) were aged <5, 5-19, and ≥20 years, respectively. We observed a general decline in classic presentation and severe disease with an increase in the number of doses, and less complications among children aged 5-19 years compared to other age-groups. Among 93 breakthrough cases with avidity results, 11 (12%) and 76 (82%) were classified as PVF and SVF, respectively, with a higher proportion of PVFs having a classic measles presentation and severe disease than SVFs. Breakthrough measles cases tended to have milder disease with less complications. A small proportion of breakthrough infections were due to PVF than SVF. It is critical to maintain high MMR vaccination coverage in the United States to prevent serious measles illnesses.

Clinical characteristics of pyoderma gangrenosum: Case series and literature review.

Pyoderma gangrenosum (PG) is a neutrophilic skin disease characterized by recurrent painful cutaneous ulcers, often accompanied by inflammatory bowel disease, joint pain, and other systemic damage. This disease is relatively rare in clinical practice and its diagnosis and treatment are often delayed, leading to secondary infections in the skin lesions, prolonged disease course, and increased disease burden on patients. This study retrospectively analyzed the clinical characteristics and treatment strategies of patients with PG admitted to our hospital and conducted a literature review, in order to improve the understanding of the disease among clinical doctors, enable patients to receive better diagnosis and treatment, and ultimately improve patient prognosis. Clinical data of patients diagnosed with PG and hospitalized in Beijing Chaoyang Hospital, Capital Medical University from January 2014 to December 2022 were retrospectively collected. The clinical manifestations, treatment strategies, efficacy, and disease outcomes were analyzed. A total of 14 patients, including 8 males and 6 females, aged 14 to 66 years, were included. Skin lesion types: 13 cases were ulcer-type, 1 case was pustule combined with ulcer-type, and the lower limbs were the most commonly affected areas. All the 14 patients presented with comorbidities. All patients were treated with glucocorticoids, with a daily dose equivalent to 20 to 100 mg prednisone and a median dose of 40 mg. Among them, 3 patients were treated with minocycline in combination, 1 patient was treated with mycophenolate mofetil 0.5 twice daily in combination, 1 patient was treated with cyclophosphamide 0.1 once daily in combination, and 1 patient was treated with thalidomide 0.1 every night in combination. PG is a relatively rare immune-related skin disease. Our small sample data analysis found that male PG is not uncommon in the Chinese population. Systemic glucocorticoids can quickly control the symptoms of PG in most patients with PG. In patients with poor efficacy or limited use of glucocorticoids, immunosuppressive drugs or novel targeted drugs such as biologics or small-molecule drugs should be used in combination as early as possible. Skin lesion care focuses on preventing infection, avoiding surgical debridement, and emphasizing pain management and the symptomatic treatment of comorbidities.

274 Evaluation of recombinant Capripoxvirus antigens in the development of indirect enzyme linked immunosorbent assays

Abstract Capripoxvirus is a genus of DNA viruses that includes sheep pox virus, goat pox virus and lumpy skin disease virus (LSDV). These viruses are considered high consequence viruses due to the severe clinical disease leading to economic losses to production and impact on trade. The recent spread of LSDV in Europe and Asia has demonstrated the transboundary nature of LSDV. The vaccines used to control Capripoxvirus infections currently do not have the ability to differentiate infected from vaccinated animals (DIVA) and the enzyme linked immunosorbent assays (ELISA) available for detection of antibodies to Capripoxvirus infections are not ideal. Previous research has been done to evaluate different Capripoxvirus antigens using E. coli expressed antigens; however, there has been no prior evaluation of baculovirus expressed Capripoxvirus antigens for use in ELISA. The objective of the current research was to produce 6 recombinant Capripoxvirus antigens using a baculovirus expression vector system (BEVS) and to evaluate these antigens in ELISAs to test bovine, sheep, and goat serum. The sequences used to produce the recombinant antigens were based on a consensus obtained using reference genomes consisting of all three viruses within the genus. All six antigens were produced and purified in-house using BEVS followed by benchtop or FPLC purification (Figure 1). To date, the antigens have been fully validated for performance in indirect ELISA using sheep sera (Figure 2) and partially using cattle sera, with goat sera validation to follow. The ELISAs were developed and optimized using known reference sera as controls. The performance of the ELISAs developed was assessed in comparison with the only commercially available Capripoxvirus serological test. The results demonstrate that some of the antigens used for the ELISAs completely outperformed the commercial test. Several antigens were found to be useful for ELISAs to detect responses in sheep and cattle sera. The sensitivities and specificities of the different ELISAs for sheep sera ranged from 99.54% to 53.57% sensitivity and 99.54 to 94.95% specificity with likelihood ratios above 10 using receiver operating characteristic curve analysis, while the commercial kit had a 42.85% sensitivity using the same positive sheep serum panel evaluated. The development of these serological assays allows for the simultaneous evaluation of immunogenicity of Capripoxvirus antigens through the testing of serum from experimentally infected animals. This study demonstrates the proof of principle, that sensitive and specific ELISAs can be developed for Capripoxviruses.

Clinical, Radiological and Pathological Features of a Large American Cohort of Spinocerebellar Ataxia (SCA27B).

Spinocerebellar ataxia 27B due to GAA repeat expansions in the fibroblast growth factor 14 (FGF14) gene has recently been recognized as a common cause of late-onset hereditary cerebellar ataxia. Here we present the first report of this disease in the US population, characterizing its clinical manifestations, disease progression, pathological abnormalities, and response to 4-aminopyridine in a cohort of 102 patients bearing GAA repeat expansions. We compiled a series of patients with SCA27B, recruited from 5 academic centers across the United States. Clinical manifestations and patient demographics were collected retrospectively from clinical records in an unblinded approach using a standardized form. Post-mortem analysis was done on 4 brains of patients with genetically confirmed SCA27B. In our cohort of 102 patients with SCA27B, we found that SCA27B was a late-onset (57 ± 12.5 years) slowly progressive ataxia with an episodic component in 51% of patients. Balance and gait impairment were almost always present at disease onset. The principal finding on post-mortem examination of 4 brain specimens was loss of Purkinje neurons that was most severe in the vermis most particularly in the anterior vermis. Similar to European populations, a high percent of patients 21/28 (75%) reported a positive treatment response with 4-aminopyridine. Our study further estimates prevalence and further expands the clinical, imaging and pathological features of SCA27B, while looking at treatment response, disease progression, and survival in patients with this disease. Testing for SCA27B should be considered in all undiagnosed ataxia patients, especially those with episodic onset. ANN NEUROL 2024.