Search Results (1,227)

Background and Clinical Significance: Sarcina ventriculi is a rare Gram-positive coccus that thrives in acidic environments such as the human stomach. It has been increasingly identified in individuals with delayed gastric emptying and has been reported in association with various gastric disorders. However, its exact pathogenic role is not fully understood and remains controversial. Case Presentation: We present two cases of patients, one with a small bowel obstruction and the other with epigastric pain, both diagnosed with Sarcina ventriculi infection by histological examination of gastric biopsies. The patients were managed with a combination of antibiotics and a proton pump inhibitor, resulting in symptom resolution and clearance of Sarcina ventriculi upon follow-up examinations. Conclusions: This report explores the pathogenicity of Sarcina ventriculi by documenting its presence in symptomatic patients without other identifiable pathogens and demonstrating complete symptom resolution following targeted therapy. These findings raise the possibility of Sarcina ventriculi’s pathogenic potential under specific clinical conditions, suggesting it may act as more than a benign colonizer. Full article

Fragile X syndrome (FXS) is the most common form of X-linked intellectual disability (ID). This study aimed to share 30 years of experience in diagnosing FXS and determine its frequency in Thailand. We retrospectively reviewed 1480 unrelated patients (1390 males and 90 females) with ID, developmental delay, or autism spectrum disorder, or individuals referred for FXS DNA testing at Songklanagarind Hospital, Thailand, over a 30-year period. The samples were analyzed using cytogenetic methods, PCR-based techniques, and/or Southern blot analysis. Full mutations (>200 CGG repeats) were identified in 100 males (7.2%) and three females (3.3%). An intermediate allele was detected in one male, while no premutation was found in the index cases. Two males were suspected to have FMR1 gene deletions. Twelve families underwent prenatal testing during this study. Most families undergoing prenatal FXS diagnosis involved mothers who were premutation carriers and had given birth to children affected by FXS. This study represents the largest series of molecular genetic FXS testing cases reported in Thailand. The frequency of FXS identified in different cohorts of Thai patients across various periods was approximately 7%. This study enhances public awareness of at-risk populations and highlights the importance of prenatal testing and genetic counseling for vulnerable families. Full article

Background: Cardiac involvement is common in Fabry disease (FD) and typically manifests with left ventricular hypertrophy (LVH). Patients with FD are frequently misdiagnosed, and this is mainly related to the lack of disease awareness among clinicians. The aim of this study was to determine whether providing a targeted educational intervention on FD may enhance FD diagnosis. Methods. This research was designed as a single-arm before-and-after intervention study and evaluated the impact of providing a specific training on FD to cardiologists from different Italian centers, without experience in rare diseases. In the 12-month period after the educational intervention, the rate of FD screening and diagnosis was assessed and compared with those conducted in the two years preceding the study initiation. Results: Fifteen cardiologists participated to this study, receiving a theoretical and practical training on FD. In the two previous two years, they conducted 12 FD screening (6/year), and they did not detect any cases of FD. After the training, they performed 45 FD screenings, with an eight-fold rise in the annual screening rate. The screened population (age: 61 ± 11 years, men: 82%) was mainly composed of patients with unexplained LVH (n = 43). There were four new FD diagnoses and, among of them, three had a late-onset GLA variant. After the cascade genetic screening, 11 affected relatives and 8 heterozygous carriers were also detected. Conclusions: A targeted educational intervention for cardiologists allowed the identification of four new families with FD. Enhancing FD awareness is helpful to reduce the diagnostic and therapeutic delay. Full article

Background: Lysosomal storage diseases (LSDs) are a genetically and clinically heterogeneous group of inborn errors of metabolism caused by variants in genes encoding lysosomal hydrolases, membrane proteins, activator proteins, or transporters. These disease-causing variants lead to enzymatic deficiencies and the progressive accumulation of undegraded substrates within lysosomes, disrupting cellular function across multiple organ systems. While classical phenotypes typically manifest in infancy or early childhood with severe multisystem involvement, a combination of advances in molecular diagnostics [particularly next-generation sequencing (NGS)] and improved understanding of disease heterogeneity have enabled the identification of attenuated forms characterised by residual enzyme activity and later-onset presentations. These milder phenotypes often evade early recognition due to nonspecific or isolated symptoms, resulting in significant diagnostic delays and missed therapeutic opportunities. Objectives/Methods: This study characterises the clinical, biochemical, and molecular profiles of 10 adult patients diagnosed with LSDs, all representing attenuated forms, and discusses them alongside a narrative review. Results: Enzyme activity, molecular data, and phenotypic assessments are described to explore genotype–phenotype correlations and identify diagnostic challenges. Conclusions: These findings highlight the variable expressivity and organ involvement of attenuated LSDs and reinforce the importance of maintaining clinical suspicion in adults presenting with unexplained cardiovascular, neurological, ophthalmological, or musculoskeletal findings. Enhanced recognition of atypical presentations is critical to facilitate earlier diagnosis, guide management, and enable cascade testing for at-risk family members. Full article

Background: Urine microbial analysis is a frequently requested test that is often associated with contamination during specimen collection or storage, which leads to false-positive diagnoses and delayed reporting. In the era of digitalization, machine learning (ML) can serve as a valuable tool to support clinical decision-making. Methods: This study investigates the application of a simple artificial neural network (ANN) to pre-identify negative and contaminated (false-positive) specimens. An ML model was developed using 8181 urine samples, including cytology, dipstick tests, and culture results. The dataset was randomly split 2:1 for training and testing a multilayer perceptron (MLP). Input variables with a normalized importance below 0.2 were excluded. Results: The final model used only microbial and either urine color or urobilinogen pigment analysis as inputs; other physical, chemical, and cellular parameters were omitted. The frequency of positive and negative specimens for bacteria was 6.9% and 89.6%, respectively. Contaminated specimens represented 3.5% of cases and were predominantly misclassified as negative by the MLP. Thus, the negative predictive value (NPV) was 96.5% and the positive predictive value (PPV) was 87.2%, leading to 0.82% of the cultures being unnecessary microbial cultures (UMC). Conclusions: These results suggest that the MLP is reliable for screening out negative specimens but less effective at identifying positive ones. In conclusion, ANN models can effectively support the screening of negative urine samples, detect clinically significant bacteriuria, and potentially reduce unnecessary cultures. Incorporating morphological information data could further improve the accuracy of our model and minimize false negatives. Full article

Background: Aortic stenosis (AS) has long been considered a degenerative disease and is typically diagnosed in older men at an advanced stage. However, accumulating evidence has highlighted the similarities between AS and atherosclerosis, particularly regarding shared risk factors and overlapping pathophysiological mechanisms. This connection has led to a paradigm shift, suggesting that AS may be preventable in its early stages. Methods: This narrative review synthesizes the existing literature exploring the parallels between AS and atherosclerosis, focusing on common risk factors, pathogenic pathways, and evolving therapeutic strategies. Clinical trials and translational studies were examined to assess the effectiveness of atherosclerosis-based treatments for AS. Results: Multiple studies have confirmed the shared inflammatory, lipid-mediated, and calcific mechanisms of AS and atherosclerosis. Despite these similarities, therapeutic strategies effective in atherosclerosis, such as statin therapy, have not consistently shown benefits in AS. New medical approaches aim to delay aortic valve replacement and reduce the associated morbidity. The partially overlapping pathogenesis continues to guide future research. Conclusions: While AS and atherosclerosis share several pathogenic features, their clinical courses and treatment responses diverge. Understanding the limits and potential of their overlap may inform future preventive and therapeutic strategies. Earlier detection and targeted intervention in AS remain key goals, drawing on insights from cardiovascular disease management. Full article

Rubinstein–Taybi Syndrome type 1 (RSTS1) is an uncommon autosomal dominant genetic disorder associated with neurodevelopmental impairments and multiple congenital anomalies, with an incidence of 1:100,000–125,000 live births. The syndrome, caused by de novo mutations in the CREBBP gene, is characterized by phenotypic variability, including intellectual disability, facial dysmorphisms, and systemic abnormalities. The current case report describes a 15-year-old Brazilian female diagnosed with RSTS1 through whole-exome sequencing, which identified a de novo heterozygous missense mutation in the CREBBP gene (NM_004380.3; c.4393G > C; p.Gly1465Arg), classified as pathogenic. The patient’s clinical presentation included facial dysmorphisms, skeletal abnormalities, neurodevelopmental delay, psychiatric conditions, and other systemic manifestations. A comprehensive genetic counseling process facilitated the differential diagnosis and management strategies, emphasizing the importance of early and precise diagnosis for improving clinical outcomes. This report contributes to the growing knowledge of the genotype–phenotype correlations in RSTS1, aiding in the understanding and management of this uncommon condition. Full article

Background: Down syndrome (DS) is a genetic disorder characterized by an extra copy of chromosome 21, often leading to intellectual disabilities, developmental delays, and an increased risk of various comorbidities, including thyroid dysfunction and mental health disorders. The relationship between thyroid dysfunction and mood disorders, particularly depression in DS populations, requires further investigation. Objective: This study aims to investigate the presence of a correlative relationship between hypothyroidism and depression in 178,840 individuals with DS, utilizing data from the National Inpatient Sample (NIS) to determine if those with comorbid hypothyroidism exhibit higher rates of depression compared to their counterparts without hypothyroidism. Methods: A retrospective analysis of the 2016–2019 NIS dataset was conducted, focusing on patients with DS, hypothyroidism, and depression diagnoses. The diagnoses were determined and labeled based on ICD-10 codes associated with NIS datapoints. Survey-weighted linear regression analyses were employed to assess the association between hypothyroidism and depression within the DS cohort, adjusting for demographic factors such as age, gender, and race. Results: This study found that individuals with DS exhibit a significantly higher prevalence of hypothyroidism (29.88%) compared to the general population (10.28%). Additionally, individuals with DS and comorbid hypothyroidism demonstrated a higher prevalence of depression (8.67%) compared to those without hypothyroidism (3.00%). These findings suggest a significant association between hypothyroidism and increased depression risk among individuals with DS. However, the overall prevalence of depression in DS (4.69%) remains substantially lower than in the general population (12.27%). Conclusions: This study highlights the importance of considering hypothyroidism as a potential contributor to depression in individuals with DS. Further research is needed to explore the underlying mechanisms of this association and potential screening and management strategies to address thyroid dysfunction and its potential psychiatric implications in DS. Full article

Background/Objectives: Chronic pain and eating disorders are two prevalent and disabling pediatric health concerns, with serious, life-threatening consequences. These conditions can co-occur, yet little is known about best practices addressing comorbid pain and eating disorders. Delayed intervention for eating disorders may have grave implications, as eating disorders have one of the highest mortality rates among psychological disorders. Moreover, chronic pain not only persists but worsens into adulthood when left untreated. This study aimed to understand pediatric clinicians’ experiences with adolescents with chronic pain and eating disorders. Methods: Semi-structured interviews were conducted with hospital-based physicians (N = 10; 70% female; M years of experience = 15.3) and psychologists (N = 10; 80% female; M years of experience = 10.2) specializing in anesthesiology/pain, adolescent medicine/eating disorders, and gastroenterology across the United States. Audio transcripts were coded, and thematic analysis was used to identify key themes. Results: Clinicians described frequently encountering adolescents with chronic pain and eating disorders. Clinicians described low confidence in diagnosing comorbid eating disorders and chronic pain, which they attributed to lack of screening tools and limited training. Clinicians collaborated with and consulted clinicians who encountered adolescents with chronic pain and/or eating disorders. Conclusions: Results reflect clinicians’ desire for additional resources, training, and collaboration to address the needs of this population. Targets for future research efforts in comorbid pain and eating disorders were highlighted. Specifically, results support the development of screening tools, program development to improve training in complex medical and psychiatric presentations, and methods to facilitate more collaboration and consultation across health care settings, disciplines, and specialties. Full article

Aspergillus can cause a spectrum of diseases depending on the immune status and predisposing conditions. Invasive pulmonary aspergillosis (IPA) is classically seen in patients with severe immunocompromise, such as patients with hematologic malignancies, transplant recipients, and chronic corticosteroid use at high doses. Recently, IPA cases in patients without these classic risk factors, including those associated with severe respiratory viral infections, chronic obstructive pulmonary disease, liver failure, and critical illness, are being increasingly recognized. Delayed recognition and missed diagnoses contribute to increased mortality in these patient populations. Maintaining a high index of suspicion and implementation of systematic screening protocols in high-risk patients may help reduce missed or delayed diagnoses and improve patient outcomes. This review describes the pathophysiology, incidence, risk factors, outcomes, and diagnostic and treatment considerations in IPA in patients with emerging risk factors. Full article

Background: Diabetes mellitus is a chronic metabolic disorder that increases mortality and morbidity rates. Infections of the hand can easily cause long-term morbidity and dysfunction, but despite their associated high morbidity, diabetic hand infections are more neglected than diabetic foot infections. Objectives: This study was conducted over a one-year follow-up period, considering the total costs of treatment over one year post discharge for patients with diabetic hand infections that required surgery. A Monte Carlo Simulation was used in this study as a sensitivity analysis of all the cost calculations. Materials and Methods: A total of 62 out of 75 patients were diagnosed with Type 2 diabetes; 11 were female, and 64 were male. Out of all the patients, 15 visited outpatient clinics 30 times or more, and due to their recurrent visits, the outpatient treatment costs reached USD 5162.41 ± 3838.55. The total cost incurred over the period from the patients’ first hospitalization to the completion of all treatments and the end of the one-year follow-up was USD 24,602.22 ± 5257.15. Conclusions: The cost of hospitalization was the most important factor affecting the total expenses. Therefore, taking precautions before a diabetic hand infection occurs, or when one does occur, performing treatment without delay is expected to reduce the economic burden. Full article

Background/Objectives: The timely initiation of antiretroviral therapy (ART) in persons living with HIV (PLWH) can improve clinical outcomes. However, ART commencement is often delayed. Portugal, despite having one of the highest new HIV diagnosis rates within the European Union, has limited available national-level data. Prior evidence from 2017 to 2018 suggests that the average time to ART initiation exceeds the recommendations for optimal patient benefits. This study aimed to determine the number of days from the first hospital appointment to the commencement of ART among newly diagnosed PLWH in Portugal between 2017 and 2022 at the national level and across different hospitals. It was hypothesized that newly diagnosed PLWH in Portugal experience a delay in ART initiation beyond the recommended timeframe. Methods: A retrospective analysis of records from Portuguese public tertiary care hospitals, which manage most HIV patients, was conducted. Descriptive statistics (measures of central tendency, dispersion, and frequency) were applied, along with association tests and a binary logistic regression model to examine factors influencing the timing of ART initiation. Results: A total of 2229 cases (out of 3434 received) from 19 hospitals were considered eligible. The median time interval between the first hospital appointment and ART initiation was 29.00 days, with a decreasing tendency between 2017 and 2022. Patients initiating therapy after 14 days had higher CD4 levels and lower viral loads compared to those starting within 14 days, with statistical significance. Conclusions: Continuous and regular monitoring of key indicators, such as the time to ART initiation, is pivotal for assessing the effectiveness of HIV treatment programs and pinpointing areas in need of improvement. Full article

We present a rare case of delayed retrobulbar and adrenal metastases from renal cell carcinoma (RCC), diagnosed 5.5 years after radical nephrectomy. The patient exhibited symptomatic orbital involvement, with imaging revealing a hypervascular retrobulbar mass and an incidental right adrenal lesion, indicative of an oligometastatic state. Owing to the patient’s refusal of surgical resection, stereotactic ablative radiotherapy (SABR) was delivered to the retrobulbar lesion at a total dose of 40 Gy in five fractions, concurrently with immune checkpoint inhibitor therapy. Treatment planning prioritized sparing adjacent critical structures, including the optic chiasm and brainstem. Follow-up over 4 years demonstrated sustained radiologic stability and volume reduction in both metastatic lesions without evidence of progression. This case underscores the potential efficacy of SABR in achieving durable local control of RCC metastases, particularly in anatomically constrained regions where surgery is unfeasible. Moreover, it highlights the value of a multidisciplinary, multimodal treatment approach incorporating advanced radiotherapy techniques and systemic immunotherapy. Lastly, it reinforces the importance of prolonged surveillance in RCC survivors due to the potential for late metastatic recurrence at uncommon sites. Full article

Background/Objectives: Bladder cancer is a malignant disease that causes more than 199,922 deaths a year globally, in which ~75% of all newly diagnosed cases are non-muscle-invasive bladder cancer (NMIBC). Despite a number of treatments available, most NMIBC patients with high-grade tumors eventually recur. To add a novel therapy to complement the deficits of the current treatments, this study assesses the antitumor activity and mechanisms of action of intravesical xenogeneic urothelial cell (XUC) treatment as monotherapy and in combination with either chemotherapy or immune checkpoint inhibition (ICI). Methods: The orthotopic NMIBC graft tumor-bearing mice were randomly assigned into different treatment groups, receiving either intravesical XUCs, gemcitabine, anti-programmed death-ligand 1 (PD-L1) antibodies alone or in combination with gemcitabine or anti-PD-1 antibodies. The tumor responses, survival, and immune reactions were analyzed. Results: Intravesical XUC treatment exhibited significantly more antitumor activity to delay tumor progression than the control group and a similar effect to chemotherapy and ICI. In addition, there were significantly higher effects in the combined groups than single treatments. Immune tumor microenvironment and immune cell proliferation, cytotoxicity, and cytokine secretion were also activated by XUC treatment. Moreover, the combined groups have the highest effects. Conclusions: In vivo and ex vivo studies showed increased antitumor efficacy and immune responses by intravesical XUC treatment in single and combined treatments, suggesting a potential utility of this xenogeneic cell immunotherapeutic agent. Intravesical XUC treatment has the potential to address the substantial unmet need in NMIBC therapy as a bladder-sparing treatment option for NMIBC. Full article

Autism Spectrum Disorder (ASD) encompasses various neurological disorders with symptoms varying by age, development, genetics, and other factors. Core symptoms include decreased pain sensitivity, difficulty sustaining eye contact, incorrect auditory responses, and social engagement issues. Diagnosing ASD poses challenges as signs can appear at early stages of life, leading to delayed diagnoses. Traditional diagnosis relies mainly on clinical observation, which is a subjective and time-consuming approach. However, AI-driven techniques, primarily those within machine learning and deep learning, are becoming increasingly prevalent for the efficient and objective detection and classification of ASD. In this work, we review and discuss the most relevant related literature between January 2016 and May 2024 by focusing on ASD detection or classification using diverse technologies, including magnetic resonance imaging, facial images, questionnaires, electroencephalogram, and eye tracking data. Our analysis encompasses works from major research repositories, including WoS, PubMed, Scopus, and IEEE. We discuss rehabilitation techniques, the structure of public and private datasets, and the challenges of automated ASD detection, classification, and therapy by highlighting emerging trends, gaps, and future research directions. Among the most interesting findings of this review are the relevance of questionnaires and genetics in the early detection of ASD, as well as the prevalence of datasets that are biased toward specific genders, ethnicities, or geographic locations, restricting their applicability. This document serves as a comprehensive resource for researchers, clinicians, and stakeholders, promoting a deeper understanding and advancement of AI applications in the evaluation and management of ASD. Full article