Search Results (3,362)

Eosinophilic Granulomatosis with Polyangiitis (EGPA) is a rare systemic vasculitis with eosinophilic inflammation and variable clinical presentations. Although skin manifestations are frequent, current classification criteria do not include them, which may underestimate their diagnostic value. This prospective observational study aimed to assess systemic and skin involvement as well as eosinophilia, anti-neutrophil cytoplasmic antibody (ANCA), and Anti-nuclear antibodies (ANA) serum levels in 20 EGPA patients followed for one year at the University Hospital of Messina, Italy, before starting Mepolizumab, 300 mg. Eosinophilia, ANCA status, systemic and skin involvement were also evaluated at 6 and 12 months; a literature review on these data supplements our findings. Skin involvement was present in 55% of patients, including purpura, urticarial vasculitis, angioedema, maculopapular rash, and nodules, mostly in ANCA-negative patients, though purpura was more frequent in ANCA-positive cases but without any statistically significant correlation. ANAs were present in 50% of patients, together with ANCA in two subjects and without in eight. Mepolizumab significantly reduced eosinophil levels, BVASs, and corticosteroid dependence, with notable improvement in skin symptoms. In conclusion, skin manifestations are common in EGPA and may represent useful indicators of disease activity. Their integration with ANCA status, eosinophil counts, and positivity to other autoantibodies could enhance diagnostic and monitoring strategies identifying different clusters of EGPA patients even if the small sample size limits the generalizability of the findings. Full article

Chromosomal microarray analysis (CMA) was performed for 40 patients with B-ALL undergoing treatment according to the ALL-2016 protocol to investigate the copy number alterations (CNAs) and copy neutral loss of heterozygosity (cnLOH) associated with minimal residual disease (MRD)-positive remission. Aberrations involving over 20,000 genes were identified, and a random forest approach was applied to isolate a subset of genes whose CNAs and cnLOH are significantly associated with poor therapeutic response. We have assembled the triple matched healthy population data and used that data as a reference, but not as a matched control. We identified a recurrent cluster of cnLOH in the 19q13.2–19q13.31 region, significantly enriched in MRD-positive patients (70% vs. 47% in the reference group vs. 16% in MRD-negative patients). This region includes the pregnancy-specific glycoprotein (PSG) gene family and the oncogene ERF, suggesting a potential role in leukemic persistence and treatment resistance. Additionally, we observed significant deletions involving 7p22.3 and 16q13, often as part of large-scale losses affecting almost the entire chromosomes 7 and 16, indicative of global chromosomal instability. These findings highlight specific genomic regions potentially involved in therapy resistance and may contribute to improved risk stratification in B-ALL. Our findings emphasize the value of high-resolution CMA in diagnostics and risk stratification and suggest that PSG genes and other candidate genes could serve as biomarkers for predicting treatment outcomes. Full article

Background: Fibromyalgia (FM) is a chronic condition characterized by widespread pain, fatigue, cognitive difficulties, and psychological symptoms. Patients often present distinct personality traits and psychopathological patterns associated with symptom severity. Objective: To examine psychopathological profiles in FM patients based on functional, physical–somatic, and emotional impairment domains, as well as on cumulative disease severity. Materials and Methods: A cross-sectional study was conducted with 70 women clinically diagnosed with FM at a specialized Fibromyalgia Unit. Psychological functioning was assessed using the Personality Assessment Inventory, and disease impact was measured with the Fibromyalgia Impact Questionnaire. Hierarchical cluster analyses were used to classify participants into mild and severe clusters across FIQ domains, and psychological profiles were compared. Results: Patients with severe functional impairment had more affective dysregulation (76.43 vs. 70.20, p < 0.01) and somatic complaints (85.57 vs. 79.76, p < 0.05) than those with mild impairment. The severe–physical cluster showed greater mood instability, somatization, and suicidal ideation (60.94 vs. 53.61, p < 0.05). The severe–emotional cluster had higher rates of major depression (85.71% vs. 64.28%) and persistent depressive disorder (76.19% vs. 70.61%, p < 0.05). Severe showed more emotional instability and somatization, distinguishing it from mild. Greater cumulative severity intensified depressive and somatic disorders. Discussion: Findings support FM’s biopsychosocial profile, where emotional distress may relate to psychological and physical symptoms, reinforcing the need for personalized, multidisciplinary care and comprehensive assessment. Full article

Affecting over 50% of stroke patients, dysphagia is still challenging to diagnose and manage due to its complex multifactorial nature and can be the result of disruptions in the coordination of cortical and subcortical neural activity as reflected in electroencephalographic (EEG) signal patterns. Sample Entropy (SampEn), a signal complexity or predictability measure, could serve as a tool to identify any abnormalities associated with dysphagia. The present study aimed to identify quantitative dysphagia biomarkers using SampEn from EEG recordings in post-stroke patients. Sample entropy was calculated in the theta, alpha, and beta bands of EEG recordings in a repetitive swallowing task performed by three groups: 22 stroke patients without dysphagia (controls), 36 stroke patients with dysphagia, and 21 healthy age-matched individuals. Post-stroke patients, both with and without dysphagia, exhibited significant differences in SampEn compared to healthy subjects in the alpha and theta bands, suggesting widespread alterations in brain dynamics. These changes likely reflect impairments in sensorimotor integration and cognitive control mechanisms essential for effective swallowing. A significant cluster was identified in the left parietal region during swallowing in the beta band, where dysphagic patients showed higher entropy compared to healthy individuals and controls. This finding suggests altered neural dynamics in a region crucial for sensorimotor integration, potentially reflecting disrupted cortical coordination associated with dysphagia. The precise quantification of these neurophysiological alterations offers a robust and objective biomarker for diagnosing neurogenic dysphagia and monitoring therapeutic interventions by means of EEG, a non-invasive and cost-efficient technique. Full article

Introduction: Low medication adherence and low hypertension control are a public health challenge, particularly in low- and middle-income countries (LMICs). Healthcare system- and patient-related barriers hinder the successful management of hypertension. This study aimed to identify the perceptions of barriers and facilitators to hypertension management among health system stakeholders in Santander, Colombia. Materials and Methods: We conducted a qualitative, phenomenological, and interpretative study, comprising five focus groups, to explore the barriers and facilitators to managing people with hypertension. Each focus group was formed by stakeholders from territorial entities, healthcare insurers, or healthcare providers. Meetings were held between December 2022 and February 2023. The sessions were recorded and transcribed using NVivo Transcription and analyzed using NVivo version 1.6.1. Results: Seven categories of barriers and facilitators were identified: strategies, resources, access, risk assessment, cross-sector collaboration, articulation, and stewardship. Of these categories, articulation and stewardship emerged as the main barriers, as revealed through axial coding and cluster analysis, which highlighted deficiencies in stewardship practices, a lack of clear objectives, and misalignment with public policy frameworks. Conclusions: Multisectoral actions extending beyond healthcare providers and aimed at improving coordination and intersectoral collaboration are essential for enhancing hypertension control in LMICs, such as Colombia. Addressing social determinants and strengthening primary healthcare through community-based strategies are critical, making stewardship and improved access key priorities. Full article

Background: Despite significant advancements in diabetes care, many individuals with type 2 diabetes (T2D) do not receive optimal care and treatment. Digital interventions promoting behavioral changes have shown promising long-term results in supporting healthier lifestyles but are not implemented in most healthcare offerings, maybe due to lack of general practice support and collaboration. This study evaluates the efficacy of the Digital, Individualized, and Collaborative Treatment of T2D in General Practice Based on Decision Aid (DICTA), a randomized controlled trial integrating a patient-centered smartphone application for lifestyle support in conjunction with a clinical decision support (CDS) tool to assist general practitioners (GPs) in optimizing antidiabetic treatment. Methods: The present randomized controlled trial aims to recruit 400 individuals with T2D from approximately 70 GP clinics (GPCs) in Denmark. The GPCs will be cluster-randomized in a 2:3 ratio to intervention or control groups. The intervention group will receive one year of individualized eHealth lifestyle coaching via a smartphone application, guided by patient-reported outcomes (PROs). Alongside this, the GPCs will have access to the CDS tool to optimize pharmacological decision-making through electronic health records. The control group will receive usual care for one year, followed by the same intervention in the second year. Results: The primary outcome is the one-year change in estimated ten-year cardiovascular risk, assessed by SCORE2-Diabetes calculated from age, smoking status, systolic blood pressure, total and high-density lipoprotein cholesterol, age at diabetes diagnosis, HbA1c, and eGFR. Conclusions: If effective, DICTA could offer a scalable, digital-first approach for improving T2D management in primary care by combining patient-centered lifestyle coaching with real-time pharmacological clinical decision support. Full article

Background: In childhood acute lymphoblastic leukemia (ALL), in addition to classical chromosomal abnormalities, loss of heterozygosity (LOH), including copy-neutral LOH, is also observed. While LOH has been described in the literature, its clinical relevance in pediatric ALL remains unclear. The aim of this study is to identify and analyze patterns of LOH, assess their frequency, and evaluate their association with clinical characteristics and early treatment response during the induction phase of the ALL protocol. Methods: The study included 853 pediatric ALL patients, of whom 120 had B-ALL LOH+ and 58 had T-ALL LOH+. LOH was analyzed using CytoScan HD SNP microarrays. Patients were stratified using multiple correspondence analysis (MCA) and hierarchical clustering on principal components (HCPC), which identified three genetically and clinically distinct clusters. Results: In B-ALL, two clusters with extensive LOH—particularly involving chromosome 9—were associated with poor prognosis and suboptimal response to therapy. In contrast, Cluster 2, characterized by CDKN2A duplication and rare LOH, showed a favorable clinical course. In T-ALL, Cluster 1 had LOH in CDKN2A but favorable outcomes; Cluster 2 exhibited biallelic CDKN2A deletion and aggressive disease; Cluster 3 lacked CDKN2A alterations and showed a genetically stable profile. LOH was common on chromosomes not typically affected by trisomy and rare on those gained. Conclusions: Our study indicates that LOH profiling can positively influence patient stratification by identifying high-risk subgroups, inform prognosis by highlighting unfavorable genetic alterations, and help predict poor treatment response in specific clinical profiles. Full article

Purpose: The adenoid microbiota plays a key role in adenoid hypertrophy (AH). This study explored the molecular epidemiology and antimicrobial resistance of Haemophilus. Influenzae (H. influenzae) strains in pediatric AH patients. Methods: Retrospective analysis of pediatric AH patients undergoing endoscopic adenoidectomy. Adenoid tissue samples were cultured to screen for pathogens. H. influenzae strains were identified by 16S rRNA sequencing and serotyped via q-PCR. Multilocus sequence typing (MLST) and ftsI gene analysis were conducted using PubMLST. β-lactamase genes (bla_TEM-1, bla_ROB-1) were detected by PCR, and antibiotic susceptibility testing (AST) was performed using the Etest method. For imipenem-resistant strains, the acrRAB efflux pump gene cluster and ompP2 porin gene were sequenced and compared with those of the wild-type strain Rd KW20. Results: Over 8 months, 56 non-duplicate H. influenzae strains were isolated from 386 patients. The detection rate was highest in children under 5 years (30.5%) compared to those aged 5–10 years (13.4%) and 10–15 years (8.7%). Of 49 sub-cultured strains, all were non-typeable H. influenzae (NTHi). MLST identified 22 sequence types (STs) and 13 clonal complexes (CCs), with CC11 (26.5%), CC3 (14.3%), and CC107 (14.3%) being predominant. Common STs included ST103 (22.4%), ST57 (10.2%), and ST107 (10.2%). Most strains belonged to the ftsI group III-like+ (57.1%). β-lactamase positivity was 98.0% (48/49), with bla_TEM-1 (95.9%) and bla_ROB-1 (18.4%) detected. AST showed low susceptibility to ampicillin (10.2%), amoxicillin–clavulanate (34.7%), azithromycin (12.2%), and trimethoprim–sulfamethoxazole (14.3%). Among the β-lactamase-positive strains, 44/48 were β-lactamase-positive ampicillin-resistant (BLPAR); none were β-lactamase-negative ampicillin-resistant (BLNAR). Imipenem susceptibility was 91.8% (45/49). No carbapenemases were found in the imipenem-resistant strains, but mutations in acrRAB (88.12–94.94% identity) and ompP2 (77.10–82.94% identity) were observed. Conclusions: BLPAR NTHi strains of CC11 are major epidemic strains in pediatric AH. Imipenem resistance in H. influenzae likely results from porin mutations rather than carbapenemase activity. Enhanced surveillance of H. influenzae’s role in AH and its resistance patterns is warranted. Full article

Interferon (IFN) signaling plays vital roles in host defense against viral infection. However, a variety of observations have been reported in the literature regarding the roles of IFN signaling in COVID-19. Thus, it would be important to reach a clearer picture regarding the activation or suppression of IFN signaling in COVID-19. In this work, regulation of marker genes for IFN signaling was examined in natural infection, viral challenge, and vaccination based on 13 public transcriptome datasets. Three subsets of interferon-stimulated genes (ISGs) were selected for detailed examination, including one set of marker genes for type I IFN signaling (ISGa) and two sets of marker genes for type II IFN signaling (IFN-γ signaling, GBPs for the GBP gene cluster, and HLAd for the HLA-D gene cluster). In natural infection, activation of ISGa and GBPs was accompanied by the suppression of HLAd in hospitalized patients. Suppression of GBPs was also observed in certain critical conditions. The scale of regulation was much greater for ISGa than that of GBPs and HLAd. In addition, the suppression of HLAd was correlated with disease severity, and it took much longer for HLAd to return to the level of healthy controls than that for ISGa and GBPs. Upon viral challenge, the activation of ISGa and GBPs was similar to that of natural infection, while the suppression of HLAd was not observed. Moreover, GBPs’ return to the pre-infection level was at a faster pace than that of ISGa. Upon COVID-19 vaccination, activation was observed for all of these three gene sets, and the scale of activation was comparable for ISGa and GBPs. Notably, it took a much shorter time for GBPs and ISGa to return to the level of healthy controls than that in COVID-19 infection. In addition, the baseline values and transient activation of these gene sets were also associated with subsequent vaccination response. The intricate balance of IFN signaling was demonstrated in mild breakthrough infection, where attenuated response was observed in people with prior vaccination compared to that in vaccine-naïve subjects. Overall, distinctive temporal profiles of IFN signaling were observed in natural infection, viral challenge, and vaccination. The features observed in this work may provide novel insights into the disease management and vaccine development. Full article

Background/Objectives: Non-fermenting Gram-negative bacilli (NFGNB) represent a significant clinical challenge due to their intrinsic and acquired resistance, particularly in immunocompromised patients. Infections cause by NFGNB are associated with high morbidity and mortality, especially among patients with cystic fibrosis and hematologic malignancies. This study aimed to assess the in vitro susceptibility of clinically relevant NFGNB isolates to two newer antibiotics, cefiderocol and aztreonam/avibactam, and an established antibiotic, trimethoprim/sulfamethoxazole. Methods: This retrospective, monocentric study analysed 94 NFGNB isolates (30 Pseudomonas aeruginosa, 30 Acinetobacter sp., 24 Stenotrophomonas maltophilia, and 10 Burkholderia cepacia complex). Susceptibility testing for cefiderocol, aztreonam/avibactam, and trimethoprim/sulfamethoxazole was conducted using gradient strip method. MIC values were interpreted using EUCAST breakpoints, ECOFFs, or alternative criteria when necessary. Results: All S. maltophilia isolates were susceptible to cefiderocol (FCR) and aztreonam/avibactam (A/A) based on ECOFFs, with one strain resistant to trimethoprim–sulfamethoxazole (COT). Burkholderia cepacia complex strains also showed high susceptibility to FCR, with only one isolate exceeding the ECOFF for A/A, and 20% resistant to COT. All Acinetobacter sp. isolates were susceptible to FCR; however, most MIC values clustered at or just below the ECOFF value. In P. aeruginosa, one isolate was resistant to FCR, and three isolates (10%) were resistant to A/A. Interestingly, confirmed carbapenemase producers remained susceptible to both FCR and A/A. Most A/A MIC values for P. aeruginosa were just below the ECOFF. Conclusions: Cefiderocol and aztreonam/avibactam demonstrated promising in vitro activity against clinically relevant NFGNB, including carbapenem-resistant strains. These findings support their potential role as therapeutic options for difficult-to-treat infections, particularly in immunocompromised patients. Full article

Background/Objectives: Obstructive sleep apnea (OSA) is a highly prevalent disorder that significantly impacts quality of life and daily functioning. While continuous positive airway pressure (CPAP) therapy is effective, long-term adherence remains a challenge. This single-arm observational study aimed to evaluate clinical outcomes and adherence patterns during telemedicine-supported CPAP therapy and identify distinct phenotypic response clusters in Romanian patients with OSA. Methods: This prospective observational study included 86 adults diagnosed with OSA, treated with ResMed Auto CPAP devices at “Victor Babeș” University Hospital in Timișoara, Romania. All patients were remotely monitored via the AirView™ platform and received monthly telephone interventions to promote adherence when necessary. Clinical outcomes were assessed through objective telemonitoring data. K-means clustering and t-distributed stochastic neighbor embedding (t-SNE) were employed to explore phenotypic response patterns. Results: During telemedicine-supported CPAP therapy, significant clinical improvements were observed. The apnea–hypopnea index (AHI) decreased from 42.0 ± 21.1 to 1.9 ± 1.3 events/hour. CPAP adherence improved from 75.5% to 90.5% over six months. Average daily usage increased from 348.4 ± 85.8 to 384.2 ± 65.2 min. However, post hoc analysis revealed significant concerns about the validity of self-reported psychological improvements. Self-esteem changes showed negligible correlation with objective clinical measures (r < 0.2, all p > 0.1), with only 3.3% of variance being explained by measurable therapeutic factors (R² = 0.033). Clustering analysis identified four distinct adherence and outcome profiles, yet paradoxically, patients with lower adherence showed greater self-esteem improvements, contradicting therapeutic causation. Conclusions: Telemedicine-supported CPAP therapy with structured monthly interventions was associated with substantial clinical improvements, including excellent AHI reduction (22-fold) and high adherence rates (+15% after 6 months). Data-driven phenotyping successfully identified distinct patient response profiles, supporting personalized management approaches. However, the single-arm design prevents definitive attribution of improvements to telemonitoring versus natural adaptation or placebo effects. Self-reported psychological outcomes showed concerning patterns suggesting predominant placebo responses rather than therapeutic benefits. While the overall findings demonstrate the potential value of structured telemonitoring for objective CPAP outcomes, controlled trials are essential to establishing true therapeutic efficacy and distinguishing intervention effects from measurement bias. Full article

Early prediction of lymph node metastasis (LNM) following neoadjuvant therapy (NAT) is crucial for timely treatment optimization in esophageal squamous cell carcinoma (ESCC). This study developed and validated a computed tomography-based radiomic model for predicting pathologically confirmed LNM status at the time of surgery in ESCC patients after NAT. A total of 469 ESCC patients from Sun Yat-sen University Cancer Center were retrospectively enrolled and randomized into a training cohort (n = 328) and a test cohort (n = 141). Three signatures were constructed: the tumor-habitat-based signature (Habitat_Rad), derived from radiomic features of three tumor subregions identified via K-means clustering; the multiple instance learning-based signature (MIL_Rad), combining features from 2.5D deep learning models; and the clinicoradiological signature (Clinic), developed through multivariate logistic regression. A combined radiomic nomogram integrating these signatures outperformed the individual models, achieving areas under the curve (AUCs) of 0.929 (95% CI, 0.901–0.957) and 0.852 (95% CI, 0.778–0.925) in the training and test cohorts, respectively. The decision curve analysis confirmed a high net clinical benefit, highlighting the nomogram’s potential for accurate LNM prediction after NAT and guiding individualized therapy. Full article

A Streptococcus suis strain isolated from the blood of a patient in Zhejiang Province, China, was analysed using whole-genome sequencing and tested for antimicrobial resistance. The isolated strain was identified as S. suis serotype 2, and classified to ST25 on multilocus sequence typing (MLST). The minimum core genome group of the strain was identified as Group 4, and multilocus variable-number tandem-repeat analysis (MLVA) assigned it as type 2, 4.4, 0, 9, 3, 2, 0, 0. An antimicrobial resistance analysis showed that the strain was resistant to clindamycin, tetracycline, azithromycin, and erythromycin but sensitive to 11 other antibiotics. In a genomic evolution analysis, this isolate clustered on the same branch as North American pig isolate, Chinese pig isolates from Tianjin, and Hubei pig isolates. Full article

Background: Regulatory T cells (Tregs) are the main suppressor cells that maintain immune tolerance and prevent autoimmunity. Changes in Treg number or function are implicated in a wide range of autoimmune and inflammatory (AI/I) diseases, with or without underlying inborn errors of immunity (IEI). Understanding the phenotypic profiles of Treg subsets and their associations with immune dysregulation is crucial to identifying potential robust and holistic biomarkers for disease activity. Methods: We examined peripheral blood mononuclear cells from 40 patients diagnosed with various autoimmune/inflammatory diseases, including those with genetically confirmed inborn errors of immunity (IEIs), and compared these samples to those from 38 healthy controls of the same age. Utilizing multiparametric flow cytometry, we measured multiple Treg sub-populations and investigated their correlations with lymphocyte subset profiles and the diversity of autoantibodies. We applied advanced statistical and machine learning techniques, such as t-SNE, k-means clustering, and ROC analysis, to analyze immunophenotypic patterns in the patients. Results: Among all Treg sub-populations, only CD4⁺CD127^lowCD25^highFOXP3⁺ Tregs showed a significant decrease in patients compared to healthy controls (p < 0.05), while other Treg phenotypes did not differ. FOXP3 expression showed reduced intensity in patients and demonstrated diagnostic potential (AUC = 0.754). Notably, this Treg subset negatively correlated with CD19⁺ B cell percentages and positively correlated with the diversity of circulating autoantibodies. Unsupervised clustering revealed three distinct immunophenotypic profiles, highlighting heterogeneity among patients and underlining FOXP3-centered immune dysregulation. Conclusions: Our results presented that patients have an impairment in the CD4⁺CD127^lowCD25^highFOXP3⁺ regulatory T cell subset, which is identified by significantly decreased frequency and decreased expression of FOXP3. Immunological heterogeneity among patients was further uncovered by unsupervised clustering, highlighting the critical role that FOXP3-centered regulatory failure plays in the pathophysiology of illness. The combined evaluation of these three immunological factors, centered around FOXP3, holds promise as an integrative tool for monitoring disease progression across various autoimmune and immunodeficient contexts. Full article

Background: Scrub typhus (ST) is caused by Orientia tsutsugamushi (OT) infection, which is transmitted to humans through the bites of infected chiggers. The clinical presentations range from mild to life-threatening multi-organ dysfunction. This report describes a cluster of ST cases involving five oil palm estate workers in Pekan district, Pahang, Malaysia. Methods: The clinical history, laboratory, and entomological investigation were conducted on the patients, including the index case and four suspected cases in the cluster. Polymerase chain reaction (PCR) tests for OT and genotyping were performed on the patients’ blood and urine samples. Serological testing by indirect immunoperoxidase (IIP) test against Rickettsial diseases was also conducted. Principal Findings: Patients presented with fever, myalgia, headache, rash, cough, and eschar. The index case developed severe ST complicated by acute kidney injury (AKI) and respiratory distress, requiring intubation and ventilation at the intensive care unit of a tertiary hospital. ST was confirmed through PCR analysis of a urine sample, showcasing a novel diagnostic approach. The other four cases were confirmed by a four-fold rise in immunoglobulin G (IgG) antibody titers. Conclusions: oil palm estate workers are at high risk for chigger exposure in Malaysia. Awareness among clinicians and the public of ST is crucial for effective prevention, accurate diagnosis, and optimal management. Full article