Search Results (738)

Background: Asymptomatic left ventricular diastolic dysfunction (LVDD) occurs in type 2 diabetes mellitus (T2DM) patients, particularly among the elderly. Aim: This study aimed to identify diastolic function changes over a 52-week follow-up and the predictive factors for LVDD in T2DM patients without atherosclerotic manifestations. Methods: Diastolic function, metabolic profile, atherogenic indexes, and subclinical inflammatory markers were assessed at baseline and after one year in 138 T2DM outpatients. All variables were compared in patients with and without LVDD across three age groups. Results: The patients were 57.86 ± 8.82 years old, 49.3% male, with a mean 5-year diabetes duration and a median HbA_1c of 7.8%. At baseline, 71 patients had grade 1 LVDD, 12 had grade 2 and 3 LVDD, and 15 had indeterminate LVDD. In the elderly group, 29 patients had LVDD. The logistic regression analysis identified age over 65 as an independent risk factor for LVDD (Exp B = 9.85, 95% CI: 1.29–75.36, p = 0.027). LVDD patients had a longer diabetes duration and a higher prevalence of diabetic neuropathy. Elderly patients had the lowest E/A, e’, lateral s’, atherogenic and Castelli risk indexes, and significantly higher E/e’, EDT, LAVI and TNF-alpha values (p < 0.05). After 52 weeks, diastolic function worsened in 27 patients, who had no significant differences compared to those with stable or improved diastolic function. Conclusions: LVDD was common in our T2DM patients without known cardiovascular disease, and age increases the LVDD risk. Echocardiographic assessment is necessary, especially in elderly T2DM patients with co-morbidities, to identify patients at risk of progression to heart failure early. Full article

Bubaline alphaherpesvirus 1 (BuHV-1) is a virus that belongs to the Varicellovirus genus within the Alphaherpesvirinae subfamily. While BuHV-1 infections in water buffaloes (Bubalus bubalis) are often subclinical, clinical manifestations have been reported. This study provides complete genome sequences of five BuHV-1 strains isolated in Argentina, marking the first genomic characterization of BuHV-1 from the Americas. Phylogenetic reconstructions based on whole-genome and coding sequences, along with analyses of glycoproteins C, D, and E, identified a distinct clade and divergent strains. Comparative genomic analyses with publicly available BuHV-1 and Bovine alphaherpesvirus 5 (BoHV-5) sequences showed nucleotide divergence of up to 1.3% among BuHV-1 strains, indicating significant intraspecific genetic diversity. Cross-neutralization assays revealed variable relationships between BuHV-1 and BoHV-5 strains. Some Argentinian BuHV-1 strains exhibited significant antigenic subtype differences compared to Bovine alphaherpesvirus 1 (BoHV-1). Recombination analyses uncovered events between BuHV-1 and bovine herpesviruses, suggesting a complex evolutionary history within mixed farming systems. The findings indicate that the monophyletic BuHV-1 clade, including the reference BuHV-1 isolate, is representative of the BuHV-1 species. The remaining strains, provisionally classified as BuHV-1 indeterminate (BuHV-1i), can be categorized based on specific clinical and antigenic properties. The identified heterogeneity has significant implications for diagnostic accuracy, vaccine development, and disease management strategies in buffalo populations worldwide. Full article

Background and Clinical Significance: Retroperitoneal fibrosis (RPF), a rare fibroinflammatory disorder, is classified into idiopathic (iRPF) and secondary (sRPF) forms, with the latter posing significant diagnostic challenges in routine clinical pathway due to atypical presentations, especially in malignancy-associated (maRPF) cases. Case Presentation: Here, we report a 38-year-old female with congenital pancreatic hypoplasia presenting with elusive hypometabolic retroperitoneal masses, initially suggestive of iRPF. Persistent CA19-9 elevation prompted histopathological evaluation, revealing poorly differentiated adenocarcinoma of indeterminate origin. Timely integrated molecular profiling identified maRPF secondary to metastatic pancreatic adenocarcinoma, revealing rare genomic alterations, including a truncating ARID1A mutation NM_006015:c.4336C>T (p. R1446*) and CCND1/FGF3/FGF4/FGF19 (11q13) co-amplification, which resolved diagnostic ambiguity and delineated disease biology. Despite identifying these molecular features, poor prognosis was predicted, and no clinically actionable targets were detected, underscoring the need for future therapeutic development. Conclusions: This paradigm highlights molecular profiling as a critical adjunct to conventional diagnostics in maRPF, bridging the gap between histopathological ambiguity and biologically grounded clinical decision-making. Full article

Medullary thyroid carcinoma (MTC) is a rare (~2–5% of all thyroid cancers) neuroendocrine thyroid malignancy originating from parafollicular C-cells of the thyroid gland with variable biological behavior and potential for early metastasis. Diagnosis, staging, and surveillance are heavily reliant on circulating biomarkers. We aimed to provide a comprehensive overview of circulating biomarkers in the management of MTC and propose an integrated, evidence-based algorithm to guide clinical decision-making using both established and emerging biomarkers. This is a narrative review on the evolving landscape of biomarker-driven management in MTC with emphasis on analytical advancements, clinical applications, and the prognostic implications of individual and combined biomarkers. Calcitonin remains the cornerstone biomarker for MTC, and new generation immunoassays have addressed several pre-analytical and analytical challenges such as pre-analytical degradation, inter-assay variability, and biological confounders. Procalcitonin (ProCT) has emerged as a stable and less interference-prone alternative or adjunct to calcitonin, which is particularly useful in cases with indeterminate calcitonin levels. Carcinoembryonic antigen (CEA) remains a useful complementary biomarker often correlating with aggressive behavior, advanced disease, and distant metastases. Kinetic evaluation (doubling times) of calcitonin and CEA offers independent prognostic information values and those < 6 months are associated with poor survival, whereas those > 2 years suggest favorable outcomes. Newer biomarkers such as pro-gastrin-releasing peptide (ProGRP) and carbohydrate antigen 19-9 (CA19-9) show potential in monitoring advanced disease and response to therapy. Their role is still under investigation but appears promising, particularly when used in conjunction with calcitonin and CEA. Our work advances a comprehensive and clinically pragmatic framework for the management of MTC by integrating established and emerging biomarkers with evidence-based algorithms, offering greater diagnostic precision, more reliable prognostic stratification, and improved personalization of follow-up and treatment strategies. Full article

Background/Objectives: Molecular testing is most commonly performed in evaluation of thyroid nodules with indeterminate Fine Needle Aspiration Biopsy (FNAB) results. However, in clinical practice, thyroidectomy may still be pursued in patients who present with clear clinical indications despite a benign molecular test result. The aim of this study is to identify clinical factors that influence the decision to proceed with surgery in the presence of a benign molecular test result. Methods: Patients who were evaluated in the outpatient clinic for thyroid nodules at one institution between January 2016 and January 2024 were retrospectively reviewed. Patients with FNAB results corresponding to Bethesda categories III or IV and a benign result on the Afirma molecular test were included. Demographic data, medical and family history, characteristics of thyroid nodules (including ultrasonographic features), surgical history, and postoperative pathology results were analyzed. Patients were divided into two groups based on clinical management—Observation (Group-1) or Thyroidectomy (Group-2)—and compared using Chi-square tests for bivariate analysis and multivariable logistic regression. Results: A total of 177 patients were included, with 87 (49.1%) in the observation group and 90 (50.9%) in the surgical group. Mean age was 55.9 ± 13.9 years and median nodule size (IQR) was 2.8 cm (1.95–4.0 cm). Bivariate analysis revealed the surgical group had significantly higher proportions of patients with compressive symptoms (p < 0.001), hyperthyroidism (p = 0.01), nodules >4 cm (p < 0.001) and documented nodule growth during follow-up (p < 0.001). Multivariate logistic regression identified the following factors as independently associated with the decision to proceed with surgery: compressive symptoms (OR: 23.2; 95%CI: 6.06–88.89; p < 0.001), hyperthyroidism (OR: 5.87; 95%CI: 1.63–21.20; p = 0.007), nodule size >4 cm (OR: 11.36; 95%CI: 3.90–33.12; p < 0.001), and increasing nodule size during follow-up (OR: 7.85; 95%CI: 2.72–22.65; p < 0.001). Conclusions: Despite a benign molecular test result, patients exhibiting compressive symptoms, hyperthyroidism, nodules larger than 4 cm, or evidence of nodule growth during follow-up are significantly more likely to undergo thyroidectomy. In such cases, molecular testing may offer limited clinical utility and could be omitted to optimize cost-effectiveness. Full article

The recent surge in the popularity of brachycephalic dog breeds has raised concerns about their predisposition to serious health issues linked to breed-specific morphological traits. This study examined the demographic characteristics, motivations, and awareness of owners regarding welfare issues in four brachycephalic breeds (French Bulldogs, Bulldogs, Pugs, Boston Terriers). Methods: A total of 497 owners of brachycephalic dogs examined over six years at an Italian university veterinary hospital were considered; a subset of 75 owners completed a structured questionnaire. Based on responses to a key multiple-choice question about the main reason for breed choice, owners were classified into three groups: trend-driven (aesthetics/fashion), value-oriented (intelligence/behavior), and indeterminate. Results: Gender distribution did not differ significantly compared to the overall population, but brachycephalic owners were significantly younger (p < 0.001). Value-oriented owners were significantly more likely (p < 0.01) to consult a veterinarian before acquisition and showed better understanding of typical respiratory issues, which did not affect their purchasing decision. Trend-driven owners were more influenced by public figures (p < 0.05) and less engaged in preventive care. Conclusion: Our findings highlight the need for pre-acquisition veterinary counseling. Veterinarians can also assist breeders by promoting awareness of the ethical risks of selecting extreme traits in dogs. Full article

Thyroid cancer is the most common endocrine malignancy, and preoperative distinction between benign and malignant nodules remains challenging, especially in cytologically indeterminate cases. Circulating microRNAs (miRNAs) have gained interest as non-invasive biomarkers due to their stability and involvement in tumorigenesis. This study aimed to assess the preoperative diagnostic value of circulating miR-146a and miR-221 in patients undergoing thyroidectomy. A total of 56 patients were included, of whom 24 had malignant and 32 had benign thyroid lesions confirmed by histopathology. Preoperative plasma levels of miR-146a and miR-221 were quantified using qRT-PCR, and relative expression was calculated with the 2^−ΔΔCt method. miR-221 expression was significantly higher in malignant cases, with an area under the ROC curve of 1.00, achieving 100% sensitivity and specificity at the optimal threshold. miR-146a showed no significant discriminatory ability. Weak correlations were observed between miRNA expression and clinical parameters such as age, TIRADS score, or thyroid volume. Logistic regression including miR-221 led to perfect separation, indicating strong predictive capacity but precluding multivariate modeling. These findings suggest that circulating miR-221 may serve as a highly accurate biomarker for thyroid malignancy and warrant further validation in larger, prospective cohorts. Full article

In the study of biomechanical models, balance represents a complex problem due to the issue of indeterminate forces while standing. In order to solve this problem, it is essential to measure the ground reaction forces (GRFs) applied to each foot independently. The present work proposes a methodology for determining the independent GRF applied to each foot while standing when only one forceplate is available. For this purpose, an analytical method is proposed to determine the distribution of vertical GRFs and the position of the independent center of pressure (CoP) in each foot. Concurrently, several neural network (NN) models are trained to improve the results obtained. This hypothesis is experimentally validated by a self-developed device that allows one to simultaneously obtain the vertical GRF and CoP location of each foot at the same time that the GRF and the global CoP location are obtained from a single forceplate. The results obtained achieve a CoP position error of less than 8% and a vertical force error of 2%. The analytical hypothesis is demonstrated to offer a satisfactory level of precision, while the NN is shown to result in considerable improvement in some cases. Full article

This literature-based review draws on studies of thirty-four fish species; most are from northern temperate regions. Fish have flexible and indeterminate growth, and often they do not reach their growth and size potential. They may become stunted with impaired growth and early maturity, chiefly as a phenotypically plastic reaction. The main causes of stunted growth are negatively density-dependent food availability and keen intraspecific competition leading to environmental stress. Typically, their growth levels off early in life as energy consumptions approach energy costs of maintenance. Females typically attain maturity soon after the energy surplus from feeding starts to decrease. Males are often more variable in size at maturity owing to alternative mating strategies, and their size at maturity depends on both species-specific mating behaviours and environmental opportunities. In polyphenic/polymorphic populations, one phenotype may be stunted and the other phenotype non-stunted; stunted individuals do not perform the required ontogenetic niche shift needed to grow larger. The adult morphology of stunted fish is typically like the morphology of juveniles. Their secondary sexual characters are less pronounced, and they phenotypically retain adaptation to their early feeding niche, which is different from that of large-growing individuals. There are open questions regarding to what extent genetics and epigenetics regulate the life histories of stunted phenotypes. Full article

An unintended consequence of cystic fibrosis (CF) newborn screening (NBS) is the identification of infants with a positive NBS who do not meet the diagnostic criteria for CF (two CF-causing variants and/or sweat chloride > 60 mmol/L). This indeterminate diagnosis is called cystic fibrosis transmembrane conductance regulator (CFTR)-related metabolic syndrome (CRMS) or CF screen positive, inconclusive diagnosis (CFSPID). CRMS/CFSPID occurs when it is not clearly known whether CFTR variants are disease-causing. In 2024, the CFTR2 classification of many CFTR variants was changed from unknown significance to either CF-causing variants or variants of varying clinical consequences (VVCCs). We conducted a meta-analysis of CRMS/CFSPID cases from manuscripts to describe how the diagnoses would change using two different variant panels: (1) only CF-causing CFTR variants (Panel_CF-causing) and (2) CF-causing variants and VVCCs (Panel_{CF-causing+VVCCs}). Using the Panel_CF-causing, 8.7% had two CF-causing variants (reclassified as CF), while 91.3% had less than two CF-causing variants (reclassified as Undetected). Using the Panel_{CF-causing+VVCCs}, 51.4% had either two VVCCs or one VVCC with one CF-causing variant detected (reclassified as CRMS/CFSPD), 39.9% had less than two CF-causing variants detected (reclassified as Undetected), and 8.7% had two CF-causing variants (reclassified as CF). In conclusion, using the updated CFTR2 classification of CFTR variants significantly decreases the number of children with CRMS/CFSPID and gives a definitive diagnosis of CF to some children while not detecting as many children who are unlikely to develop CF. Full article

Myelodysplastic syndromes/neoplasms (MDS) represent a biologically and clinically diverse group of myeloid malignancies marked by cytopenias, morphological dysplasia, and an inherent risk of progression to acute myeloid leukemia. Over the past two decades, the field has made significant advances in characterizing the molecular landscape of MDS, leading to refined classification systems to reflect the underlying genetic and biological diversity. In 2025, the treatment of MDS is increasingly individualized, guided by integrated clinical, cytogenetic, and molecular risk stratification tools. For lower-risk MDS, the treatment paradigm has evolved beyond erythropoiesis-stimulating agents (ESAs) with the introduction of novel effective agents such as luspatercept and imetelstat, as well as shortened schedules of hypomethylating agents (HMAs). For higher-risk disease, monotherapy with HMAs continue to be the standard of care as combination therapies of HMAs with novel agents have, to date, failed to redefine treatment paradigms. The recognition of precursor states like clonal hematopoiesis of indeterminate potential (CHIP) and the increasing use of molecular monitoring will hopefully enable earlier intervention/prevention strategies. This review provides a comprehensive overview of the current treatment approach for MDS, highlighting new classifications, prognostic tools, evolving therapeutic options, and ongoing challenges. We discuss evidence-based recommendations, treatment sequencing, and emerging clinical trials, with a focus on translating biological insights into improved outcomes for patients with MDS. Full article

Objectives: Oncocyte-rich indeterminate thyroid nodules (O-ITNs) present diagnostic and management challenges due to overlapping features between benign and malignant lesions and differing cytological classifications. This study aimed primarily to assess the ultrasound (US) characteristics and US-based risk of O-ITNs using the American College of Radiology Thyroid Imaging Reporting And Data Systems (ACR TI-RADS). A secondary objective was to compare the Bethesda System for Reporting Thyroid Cytopathology (BSRTC) and Italian Consensus for the Classification and Reporting of Thyroid Cytology (ICCRTC) cytological systems regarding classification and clinical management implications for O-ITNs. Methods: A retrospective study was conducted on 177 ITNs (TIR3A and TIR3B) evaluated between June 2023 and December 2024 at CTO-Alesini, Rome (Italy). Nodules were assessed with US, cytology, and histology. Oncocyte predominance was defined as >70% oncocytes on fine-needle aspiration (FNA). US features were analyzed according to ACR TI-RADS. Nodules were reclassified by BSRTC, and potential differences in clinical case management (CCM) were analyzed. Results: O-ITNs comprised 47.5% of the sample. Compared to non-O-ITNs, O-ITNs were larger and more frequently showed low-risk US features, including a higher prevalence of ACR TI-RADS 3 nodules. However, no progressive increase in the risk of malignancy (ROM) was observed across ACR TI-RADS classes within O-ITNs. Histological malignancy was identified in 47.1% of O-ITNs, a lower proportion compared to non-O-ITNs, though the difference was not statistically significant. Classification discordance with potential management impact was lower in O-ITNs (20.2%) than in non-O-ITNs (38.7%). Conclusions: O-ITNs typically exhibit benign-appearing US features and lower classification discordance between BSRTC and ICCRTC, yet US risk stratification fails to differentiate malignancy risk within O-ITNs. A tailored approach integrating cytology and cautious US interpretation is essential for optimal O-ITN management. Full article

Background: Oncocytoma and angiomyolipoma (AML) are benign renal tumors that may mimic malignant lesions on imaging. With the increasing use of partial nephrectomy (PN) for renal masses, accurate preoperative characterization of these lesions is essential. This study highlights the role of partial nephrectomy as a valuable diagnostic tool in situations where imaging is inconclusive or raises concern for malignancy without definitive confirmation. In the absence of a reliable preoperative diagnosis, partial nephrectomy provides direct histologic verification with minimal perioperative morbidity. Moreover, it offers curative potential when malignancy is present. By achieving both diagnostic certainty and renal preservation, this approach is well-suited for clinical scenarios in which imaging ambiguity might otherwise result in overtreatment through radical surgery or undertreatment Material and methods: in this retrospective study, we reviewed our 5-year experience (2019–2024), 188 partial nephrectomies—including bilateral procedures and operations on solitary kidneys—using robotic and open approaches. All of these 30 tumors were solid renal masses with indeterminate imaging features or suspicious characteristics suggestive of malignancy, further underscoring the limitations of current preoperative diagnostic modalities. Results: Histopathological evaluation confirmed benign renal tumors in 30 cases, with oncocytoma diagnosed in 18 cases (16 robotic, 2 open) and AML in 12 cases (9 robotic, 3 open). Conclusions: Even when imaging raises suspicion of malignancy or remains inconclusive, many small renal masses are ultimately confirmed as benign upon histopathological examination. This study underscores the diagnostic uncertainty associated with small renal tumors and highlights the value of partial nephrectomy as a decisive diagnostic intervention. In situations where non-invasive modalities fail to provide definitive answers, partial nephrectomy offers tissue confirmation with minimal morbidity. Furthermore, when malignancy is present, this approach ensures appropriate oncologic management while preserving renal function. Our findings support the integration of this strategy into routine clinical practice, particularly when diagnostic clarity is essential for guiding safe and effective treatment. Full article

Ovarian tumors are rare in the pediatric population, yet they are the most common type of malignancy in tumors of the female genital tract. Both non-neoplastic and neoplastic ovarian lesions are seen in children and adolescents. Most pediatric ovarian tumors are benign. Germ cell tumors constitute the majority of ovarian tumors in the pediatric cohort, and mature teratoma is the most prevalent histologic type. However, 3–8% % of ovarian tumors in children and adolescents are malignant. Accurate characterization of ovarian masses in the pediatric population is crucial to determine the appropriate treatment, which should be minimally invasive and focused on preserving fertility. Transabdominal US is the main imaging modality for the assessment of pediatric ovarian masses. MRI represents a valuable adjunct tool for the evaluation of sonographically indeterminate ovarian lesions. This technique is also recommended for tumor staging and follow-up. CT is often used in emergency situations or when there are contraindications for MRI. Imaging findings, along with clinical features and laboratory results, play a crucial role in the characterization of ovarian masses in the pediatric population. This narrative review was based on a comprehensive literature search of articles about imaging findings of ovarian masses in the pediatric population, published between 1977 and April 2025. Data were obtained from the PubMed database, using the following keywords: “imaging”, “ovarian tumors”, ovarian masses”, and “pediatric”. This article aims to provide an overview of the role of imaging in the assessment of ovarian masses in the pediatric age group. Full article

Background and Objectives: Thyroid nodules are a common endocrine disorder, with 10–15% exhibiting malignancy. Accurate differentiation of malignant and benign nodules is crucial for optimizing treatment outcomes. Current diagnostic tools, such as the Bethesda classification and fine-needle aspiration biopsy (FNAB), are limited in sensitivity and specificity, particularly in indeterminate cases. Tumor-infiltrating immune cells (TIICs) in the tumor microenvironment (TME) play a significant role in thyroid cancer progression. CD66b⁺ neutrophil-like monocytes constitute a novel subset of myeloid cells that are implicated in the modulation of anti-tumor immune responses, but their role in thyroid cancer remains unclear. Materials and Methods: Peripheral blood and thyroid nodule tissue samples were obtained from 24 patients with papillary thyroid carcinoma, and from 10 patients who underwent surgery for symptoms of tracheal compression due to benign thyroid nodules. Myeloid cell populations were assayed by flow cytometric immunophenotyping with CD45, HLA-DR, CD14, and CD66b. The data were statistically analyzed with the clinical properties of the patients. Results: The neutrophil-like monocytes, which were determined as HLA-DR⁺CD14⁺CD66b⁺ cells, found in the circulation (11.9 ± 2.4% of total mononuclear immune cells) of the patients with papillary thyroid carcinoma, were significantly elevated (p < 0.001). Accordingly, these cells were more frequently detected in tumor tissues (21.1 ± 2.1% of total tumor-infiltrating immune cells) compared to non-tumor thyroid tissues (p = 0.0231). The infiltration levels of neutrophil-like monocytes were significantly higher in malignant nodules as well as in the peripheral blood of the papillary thyroid carcinoma patients compared to the samples obtained from the patients with benign nodules. The tumor tissues exhibited increased immune cell infiltration and harbored CD66b-expressing neutrophil-like HLA-DR⁺CD14⁺ monocytic cells, which indicates an inflammatory milieu in malignant thyroid cancer. Conclusions: This study identifies neutrophil-like monocytes as a potential biomarker for differentiating malignant and benign thyroid nodules. Elevated levels of this novel subtype of immune cells in malignant tissues suggest their role in tumor progression and their utility in enhancing diagnostic accuracy. Incorporating these findings into clinical practice may refine surgical decision-making and improve outcomes through personalized diagnostic and therapeutic strategies, particularly for radioiodine-refractory thyroid cancer. Full article