Search Results (47,494)

Background: The assessment of left ventricular (LV) filling pressure in heart failure (HF) poses a diagnostic challenge, as HF patients may have normal LV filling pressures at rest but often display elevated LV filling pressures during exercise. Rapid preload increase during passive leg lift (PLL) may unmask HF in such challenging scenarios. We explored the dynamic interplay between simultaneous left atrial (LA) function and volume using LA strain/volume loops during rest and PLL and compared its diagnostic performance with conventional echocardiographic surrogates to detect elevated LV filling pressure. Methods: We retrospectively reviewed 35 patients with clinical HF who underwent simultaneous echocardiography and right heart catheterization before and immediately after PLL. Patients with atrial fibrillation (n = 4) were excluded. Twenty age-matched, healthy controls were added as controls. LA reservoir strain (LASr) was analyzed using speckle-tracking echocardiography. LA strain–volume loops were generated, including the best-fit linear regression line employing simultaneous LASr and LA volume. Results: LA strain–volume slope was lower for HF patients when compared with controls (0.71 vs. 1.22%/mL, p < 0.001). During PLL, the LA strain–volume slope displayed a moderately strong negative correlation with invasive pulmonary arterial wedge pressure (PAWP) (r = −0.71, p < 0.001). At a 0.74%/mL cut-off, the LA strain–volume slope displayed 88% sensitivity and 86% specificity to identify elevated PAWP (AUC 0.89 [0.76–1.00]). In comparison, LASr demonstrated strong but numerically lower diagnostic performance (AUC 0.82 [0.67–0.98]), and mitral E/e’ showed poor performance (AUC 0.57 [0.32–0.82]). Conclusions: In this proof-of-concept study, LA strain–volume characteristics provide incremental diagnostic value over conventional echocardiographic measures in the identification of elevated LV filling pressure. Full article

Background/Objectives: Locally advanced rectal cancer is treated with neoadjuvant chemoradiotherapy (nCRT) followed by total mesorectal excision (TME). As this approach achieves complete pathologic remissions (pCR) in approximately 30% of patients, it raises the question of whether surgery is always necessary. Non-surgical strategies, such as “watch and wait” (W&W), have shown similarly promising outcomes. However, there is an unmet need for reliable biomarkers predicting pCR. Analysis of circulating tumor DNA (ctDNA) has shown potential for monitoring treatment response and detecting minimal residual disease. We hypothesized that monitoring ctDNA changes during nCRT might facilitate the identification of individuals who achieve pCR. Methods: In the prospective single-center NEORECT trial, the plasma of forty rectal cancer patients was collected before, during, and after nCRT and before TME. Informative somatic mutations were identified in tissue biopsies by NGS and subsequently used for ctDNA quantification by dPCR. Results: The results identified three distinct ctDNA patterns: increase, decrease, and absence. Remarkably, undetectable DNA was observed in good responders, while a tenfold ctDNA increase was associated with the emergence of new metastases. Despite these insights, ctDNA alone demonstrated low specificity, with no significant correlation to pCR or long-term prognosis. A multimodal approach incorporating routinely available clinical parameters remains inadequate for accurately predicting pCR prior to TME. Conclusions: In conclusion, the NEORECT trial establishes the feasibility of ctDNA-based personalized monitoring for rectal cancer patients undergoing nCRT. However, the utility of ctDNA in enhancing pCR prediction for a W&W strategy warrants further investigation. Larger studies integrating multi-gene analyses and expanded clinical datasets are essential in the future. Full article

Background: Currently, there is a need for approaches to understand and manage the multidimensional autism spectrum and quantify its heterogeneity. The diagnosis is based on behaviors observed in two key dimensions, social communication and repetitive, restricted behaviors, alongside the identification of required support levels. However, it is now recognized that additional modifiers, such as language abilities, IQ, and comorbidities, are essential for a more comprehensive assessment of the complex clinical presentations and clinical trajectories in autistic individuals. Different approaches have been used to identify autism subgroups based on the genetic and clinical heterogeneity, recognizing the importance of autistic behaviors and the assessment of modifiers. While valuable, these methods are limited in their ability to evaluate a specific individual in relation to a normative reference sample of autistic individuals. A quantitative score based on axes of phenotypic variability could be useful to compare individuals, evaluate the homogeneity of subgroups, and follow trajectories of an individual or a specific group. Here we propose an approach by (i) combining measures of phenotype variability that contribute to clinical presentation and could impact different trajectories in autistic persons and (ii) using it with normative modeling to assess the clinical heterogeneity of a specific individual. Methods: Using phenotypic data available in a comprehensive reference sample, the Simons Simplex Collection (n = 2744 individuals), we performed principal component analysis (PCA) to find components of phenotypic variability. Features that contribute to clinical heterogeneity and could impact trajectories in autistic people were assessed by the Autism Diagnostic Interview-Revised (ADI-R), Vineland Adaptive Behavior Scales (VABS) and the Child Behavior Checklist (CBCL). Cognitive assessment was estimated by the Total Intelligence Quotient (IQ). Results: Three PCs embedded 72% of the normative sample variance. PCA-projected dimensions supported normative modeling where a multivariate normal distribution was used to calculate percentiles. A Multidimensional General Functionality Score (MGFS) to evaluate new prospective single subjects was developed based on percentiles. Conclusions: Our approach proposes a basis for comparing individuals, or one individual at two or more times and evaluating homogeneity in phenotypic clinical presentation and possibly guides research sample selection for clinical trials. Full article

Background/Objectives: Generative artificial intelligence (AI) such as ChatGPT has developed rapidly in recent years, and in the medical field, its usefulness for diagnostic assistance has been reported. However, there are few reports of AI use in dental fields. Methods: We created 20 questions that we had encountered in clinical pediatric dentistry, and collected the responses to these questions from three types of generative AI. The responses were evaluated on a 5-point scale by six pediatric dental specialists using the Global Quality Scale. Results: The average scores were >3 for the three types of generated AI tools that we tested; the overall average was 3.34. Although the responses for questions related to “consultations from guardians” or “systemic diseases” had high scores (>3.5), the score for questions related to “dental abnormalities” was 2.99, which was the lowest among the four categories. Conclusions: Our results show the usefulness of generative AI tools in clinical pediatric dentistry, indicating that these tools will be useful assistants in the dental field. Full article

A large sample of 65 individuals of the recently described goby Zebrus pallaoroi was collected in France. The species identity of these individuals was confirmed based on morphology. In addition, the species identity was validated through genetic analysis for one of the two specimens collected from the new depth records for the species. The diagnostic characters of Z. pallaoroi, originally based on a limited number of type specimens, were tested on this larger sample and critically analyzed. The diagnostic characters of Z. pallaoroi were revised, and recommendations were made for improving the study of diagnostic characters in gobiid species description, particularly when based on small sample sizes. The record of Z. pallaoroi in the western Mediterranean significantly expands its known geographic range, increases the maximum recorded depth of the species, and reveals syntopic co-occurrence with its phylogenetically closest relatives. Full article

The World Health Organization in 2021 ranked Alzheimer’s disease and other dementias as the seventh leading cause of death globally. Neurodegenerative disorders are progressive, intractable, and often fatal diseases. Early diagnosis may allow patients to enjoy prolonged survival with attenuated symptomatology because of early intervention. Hence, further research on finding non-invasive biomarkers of neurodegenerative diseases is warranted. Apolipoprotein D (ApoD) is a glycoprotein involved in lipid metabolism, oxidative stress regulation, and inflammation. It is expressed in various body fluids and regions of the central nervous system. ApoD’s roles in neuroprotection, lipid transport, and anti-inflammatory processes are crucial as far as the prevention of neurodegenerative pathologies is concerned. This review aims to summarize the background knowledge on ApoD, and it covers studies indexed in the PubMed, Scopus, and Web of Science databases. It discusses the evidence for the multifaceted roles of ApoD in the mechanisms and pathogenesis of multiple sclerosis, Alzheimer’s disease, and Parkinson’s disease. ApoD may be a specific, sensitive, easily obtained, cost-effective biomarker for neurodegenerative diseases and its applications in diagnostic practices, treatment strategies, and advancing neurodegenerative disorders’ management. Full article

Carbapenem-resistant Enterobacterales (CRE) is an emerging global concern. Specifically, carbapenemase-producing (CP) E. coli strains in CRE have recently been found in clinical, environmental, and food samples worldwide, causing many hospitalizations and deaths. Their rapid identification and characterization are paramount in control, management options, and treatment choices. Thus, this study aimed to characterize the cell surface properties of carbapenem-resistant (R) E. coli isolates and their interaction with glycan-coated magnetic nanoparticles (gMNPs) compared with carbapenem-susceptible (S) E coli. This study used two groups of bacteria: The first group included E. coli (R) isolates harboring carbapenemases and had no antibiotic exposure. Their initial gMNP–cell binding capacity, with cell surface characteristics, was assessed. In the second group, one of the E. coli (R) isolates and E. coli (S) had long-term serial antibiotic exposure, which we used to observe their cell surface characteristics and gMNP interactions. Initially, cell surface characteristics (cell morphology and cell surface charge) of the E. coli isolates were evaluated using confocal laser scanning microscope (LSCM) and a Zetasizer, respectively. The interaction of gMNPs with the E. coli isolates was assessed through LSCM and transmission electron microscope (TEM). Further, the gMNP–cell attachment was quantified as a concentration factor (CF) through the standard plating method. The results showed that the CF values of all E. coli (R) were significantly different from those of E. coli (S), which could be due to the differences in cell characteristics. The E. coli (R) isolates displayed heterogeneous cell shapes (rod and round cells) and lower negative zeta potential (cell surface charge) values compared to E. coli (S). Further, this research identified the differences in the cell surface characteristics of E. coli (S) under carbapenem exposure, compared to unexposed E. coli (S) that impact their attachment capacity. The gMNPs captured more E. coli (S) cells compared to carbapenem-exposed E. coli (S) and all E. coli (R) isolates. This study clearly found that differences in cell surface characteristics impact their interaction with magnetic nanoparticles. The gained insights aid in further understanding adhesion mechanisms to develop or improve bacterial isolation techniques and diagnostic and treatment methods for CRE. Full article

Background: Traditional imaging techniques have limited efficacy in detecting occult cervical lymph node (LN) metastases in head and neck squamous cell carcinoma (HNSCC). Positron emission tomography/computed tomography (PET-CT) has demonstrated potential for assessing HNSCC, but the literature on its efficacy for detecting cervical LN metastases is scarce and exhibits varied outcomes, hindering comparisons. Aim: To compare the efficacy of CT, MRI, PET-CT, and US for detecting LN metastasis in HNSCC with clinically negative neck lymph nodes. Methods: A systematic search was performed using Web of Science, PubMed, Scopus, Embase, and Cochrane databases. Studies comparing CT, MRI, PET-CT, or US to detect cervical metastases in HNSCC were identified. The quality of the studies was assessed using the QUADAS-2 instrument. The positive likelihood ratios (+LR) and negative likelihood ratios (−LR), sensitivity (SEN), specificity (SPE), and diagnostic odds ratio (DOR), with 95% confidence intervals (C.I.), were calculated. Analysis was stratified according to lymph node and patient basis. Results: Fifty-seven studies yielded 3791 patients. At the patient level, PET-CT exhibited the highest diagnostic performance, with a SEN of 74.5% (95% C.I.: 65.4–81.8%) and SPE of 83.6% (95% C.I.: 77.2–88.5%). PET-CT also demonstrated the highest +LR of 4.303 (95% C.I.: 3.082–6.008) and the lowest −LR of 0.249 (95% C.I.: 0.168–0.370), resulting in the highest DOR of 15.487 (95% C.I.: 8.973–26.730). In the evaluation of diagnostic parameters for various imaging modalities on node-based analysis results, MRI exhibited the highest SEN at 77.4%, and PET demonstrated the highest SPE at 96.6% (95% C.I.: 94.4–98%). PET-CT achieved the highest DOR at 24.353 (95% C.I.: 10.949–54.166). Conclusions: PET-CT outperformed other imaging modalities across the majority of studied metrics concerning LN metastasis detection in HNSCC. Full article

Background/Objectives: While new methods for measuring antimicrobial susceptibility have been associated with improved patient outcomes, they should also be validated using standard protocols for error rates and other test metrics. The objective of this study was to validate a novel susceptibility assay for complicated and recurrent urinary tract infections (UTIs): pooled antibiotic susceptibility testing (P-AST). This assay was compared to broth microdilution (BMD) and disk diffusion (DD), following Clinical and Laboratory Standards Institute (CLSI) guidelines for assessment of error rates and agreement. Methods: This study analyzed consecutive fresh clinical urine specimens submitted for UTI diagnostic testing. Upon receipt, the urine samples were subjected in parallel to standard urine culture and multiplex polymerase chain reaction (M-PCR) for microbial identification and quantification. Specimens with the same monomicrobial non-fastidious bacteria detected by both M-PCR and standard urine culture (SUC) underwent standard antibiotic susceptibility testing (AST) and P-AST antibiotic susceptibility testing. Analysis was also undertaken to assess the presence of heteroresistance for specimens with P-AST-resistant and BMD/DD consensus-susceptible results. Results: The performance measures without correction for heteroresistance showed essential agreement (EA%) of ≥90%, very major errors (VMEs) of <1.5%, and major errors (MEs) of <3.0% for P-AST, all meeting the threshold guidelines established by CLSI for AST. The categorical agreement (CA%) also met acceptable criteria (>88%), as the majority of the errors were minor (mEs) with essential agreement. The very major and major error rates for P-AST decreased to <1.0% when heteroresistance was accounted for. Conclusions: The P-AST assay methodology is validated within acceptable parameters when compared to broth microdilution and disk diffusion using CLSI criteria. Full article

In the growing field of personalized medicine, non-invasive wearable devices and sensors are valuable diagnostic tools for the real-time monitoring of physiological and biokinetic signals. Among all the possible multiple (bio)-entities, pH is important in defining health-related biological information, since its variations or alterations can be considered the cause or the effect of disease and disfunction within a biological system. In this work, an innovative (bio)-electrochemical flexible pH sensor was proposed by realizing three electrodes (working, reference, and counter) directly on a polyimide (Kapton) sheet through the implementation of CO₂ laser writing, which locally converts the polymeric sheet into a laser-induced graphene material (LIG electrodes), preserving inherent mechanical flexibility of Kapton. A uniform distribution of nanostructured PEDOT:PSS was deposited via ultrasonic spray coating onto an LIG working electrode as the active material for pH sensing. With a pH-sensitive PEDOT coating, this flexible sensor showed good sensitivity defined through a linear Nernstian slope of (75.6 ± 9.1) mV/pH, across a pH range from 1 to 7. We demonstrated the capability to use this flexible pH sensor during dynamic experiments, and thus concluded that this device was suitable to guarantee an immediate response and good repeatability by measuring the same OCP values in correspondence with the same pH applied. Full article

Background: The objective of our study was to evaluate the association and frequency of subcutaneous lymphedema in patients with gout primarily affecting the feet. Methods: In 79 patients with acute gout, ultrasound (US) and dual-energy computed tomography (DECT) were performed to assess the presence of subcutaneous edema and extra- and intra-articular gouty deposits. In addition, the diagnostic utility of two post-processing DECT protocols were evaluated, comprising different minimum attenuation thresholds of 150 HU (DECT 150 protocol) and 120 HU (DECT 120 protocol), with the same maximum attenuation threshold (500 HU) and constant kilovoltage setting of tubes A and B at 80 and 140 kVp. Results: Subcutaneous lymphedema was present in 58.2% of patients, with a significant association with extra-articular monosodium urate (MSU) deposits (p < 0.001). Specifically, 97.8% of patients with lymphedema had extra-articular MSU deposits in DECT or US examination, while no cases of lymphedema were found in patients with exclusively intra-articular deposits. The DECT 120 protocol was significantly more sensitive for detecting peripheral MSU deposits (81%) compared to the DECT 150 protocol (34.2%, p < 0.001). Conclusions: Our findings demonstrate that the presence of lymphedema in patients with gout is frequently associated with extra-articular manifestations of the disease. Full article

Latin America was one of the hotspots of COVID-19 during the pandemic. Therefore, understanding the COVID-19 mortality rate in Latin America is crucial, as it can help identify at-risk populations and evaluate the quality of healthcare. In an effort to find a more flexible and suitable model, this work formulates a new quantile regression model based on the unit ratio-Weibull (URW) distribution, aiming to identify the factors that explain the COVID-19 mortality rate in Latin America. We define a systematic structure for the two parameters of the distribution: one represents a quantile of the distribution, while the other is a shape parameter. Additionally, some mathematical properties of the new regression model are presented. Point and interval estimates of maximum likelihood in finite samples are evaluated through Monte Carlo simulations. Diagnostic analysis and model selection are also discussed. Finally, an empirical application is presented to understand and quantify the effects of economic, social, demographic, public health, and climatic variables on the COVID-19 mortality rate quantiles in Latin America. The utility of the proposed model is illustrated by comparing it with other widely explored quantile models in the literature, such as Kumaraswamy and unit Weibull regressions. Full article

Cardiac transthyretin amyloidosis is an underdiagnosed disorder with significant diagnostic difficulties due to its non-specific clinical manifestations. It is caused by the deposition of protein aggregates with an abnormal tertiary structure in the extracellular matrix. Their accumulation leads to the development of hypertrophic and restrictive cardiomyopathy and, at a later stage, heart failure with preserved ejection fraction syndrome. Depending on the pathogenesis, there are different types of the disease—hereditary and age-related wild-type transthyretin amyloidosis. We present the case of an 85-year-old woman who was referred to the department with a two-month history of exertional dyspnea in New York Heart Association functional class II. After reviewing the initial findings, several red flags for cardiac amyloidosis (CA) were identified. Following the diagnostic algorithm, scintigraphy was performed and showed significant radioisotope accumulation in the myocardium, confirming the suspected disease. In this manuscript, we present the current recommendations and diagnostic pathway, discussing in detail both available and emerging treatment options. As early diagnosis is essential to prevent the development of serious complications, we would like to highlight the pitfalls in diagnosing CA and emphasize the need to be aware of its variable clinical presentation and red flags. Full article

Acute promyelocytic leukemia (APL) accounts for approximately 10–15% of newly diagnosed acute myeloid leukemia cases and presents with coagulopathy and bleeding. Prompt diagnosis and treatment are required to minimize early mortality in APL as initiation of all-trans retinoic acid therapy rapidly reverses coagulopathy. The PML::RARA fusion is a hallmark of APL and its rapid identification is essential for rapid initiation of specific treatment to prevent early deaths from coagulopathy and bleeding and optimize patient outcomes. Given limitations and long turnaround time of current gene fusion diagnostic strategies, we have developed a novel amplification-free nanopore sequencing-based approach with low cost, easy setup, and fast turnaround time. We termed the approach CRISPR/Cas9-enriched nanopore sequencing with adaptive sampling (CENAS). Using CENAS, we successfully sequenced breakpoints of typical and atypical PML::RARA fusions in APL patients. Compared with the standard-of-care genetic diagnostic tests, CENAS achieved good concordance in detecting PML::RARA fusions in this study. CENAS allowed for the identification of sequence information of fusion breakpoints involved in typical and atypical PML::RARA fusions and identified additional genes (ANKFN1 and JOSD1) and genomic regions (13q14.13) involving the atypical fusions. To the best of our knowledge, involvements of the ANKFN1 gene, the JOSD1 gene, and the 13q14.13 genomic region flanking with the SIAH3 and ZC3H13 genes have not been reported in the atypical PML::RARA fusions. CENAS has great potential to develop as a point-of-care test enabling immediate, low-cost bedside diagnosis of APL patients with a PML::RARA fusion. Given the early death rate in APL patients still reaches 15%, and ~10% of APL patients are resistant to initial therapy or prone to relapse, further sequencing studies of typical and atypical PML::RARA fusion might shed light on the pathophysiology of the disease and its responsiveness to treatment. Understanding the involvement of additional genes and positional effects related to the PML and RARA genes could shed light on their role in APL and may aid in the development of novel targeted therapies. Full article