Search Results (4,733)

Background: Recent studies have shown that catheter ablation of atrial fibrillation leads to an improvement in mortality and a reduction in hospitalization in patients with end-stage heart failure. It is therefore hypothesized that in an end-stage heart failure population, atrial fibrillation is of great relevance and that interventional therapy is crucial to preventing further progression, especially with the aim of avoiding a heart transplant. In this paper, we describe the clinical presentation of atrial fibrillation and its management in a real end-stage heart failure cohort of patients actively waiting on a heart transplant through EUROTRANSPLANT. Methods: A total of 577 patients have been actively listed for heart transplant in our clinic. Of these, we examined all patients who were actively listed by the key date of 31.12.2024. Patients already treated by assist devices such as the left-ventricular assist device and high-urgency listed patients were excluded, as were minors and patients in need of simultaneous transplantation of other organs in addition to the heart. Results: Thirty-one patients were included in our analysis. In this cohort, 18 patients (58%) had no diagnosis of atrial fibrillation or atrial flutter. A total of 13 patients (42%) presented with atrial fibrillation or flutter: 3/13 (23%) paroxysmal, 8/13 (62%) persistent, 1/13 (8%) permanent atrial fibrillation, and 1/13 (8%) atrial flutter. Moreover, 9/13 (69%) patients with atrial fibrillation had been diagnosed during evaluation and before the active listing period for heart transplant. Only three patients developed atrial fibrillation during the active listing period (two with atypical atrial flutter, one with atrial fibrillation). In those three patients, rhythm control could be achieved: the patient with new-onset atrial fibrillation was treated by pulmonary vein ablation, and in the two patients with newly diagnosed atypical atrial flutter, electrical cardioversion was performed. Conclusions: In our real end-stage heart failure cohort, more than half of the patients do not have atrial fibrillation. Patients diagnosed with atrial fibrillation often receive their diagnosis before they are listed for heart transplant. However, atrial fibrillation is not a common cause of clinical worsening while actively waiting on a heart transplant. Full article

Classic Hodgkin lymphoma (cHL) is a distinctive B-cell malignancy defined by the presence of scarce but pathobiologically dominant Hodgkin Reed-Sternberg (HRS) cells within an inflammatory tumor microenvironment (TME). Although representing less than 10% of total tumor cellularity, HRS cells shape the TME by recruiting and functionally polarizing immune and stromal elements through cytokine- and chemokine-mediated signaling. Morphologically, HRS cells are large, atypical, often binucleated or multinucleated cells with prominent eosinophilic nucleoli and abundant cytoplasm, giving rise to the classic “owl’s eye” appearance. Distinct morphological variants—including lacunar, mummified, mononuclear, and anaplastic forms—contribute to the histopathologic diversity across cHL subtypes such as nodular sclerosis, mixed cellularity, lymphocyte-rich, and lymphocyte-depleted disease. The immunophenotype of HRS cells is equally characteristic, with strong and uniform CD30 expression, frequent CD15 positivity, reduced expression of B-cell markers (CD20, CD79A/B), and partial retention of PAX5, reflecting profound lineage dysregulation. Aberrant expression of activation markers and immune-evasion molecules, including PD-L1 driven by recurrent 9p24.1 amplification, underscores their capacity for immune escape. Genetically, HRS cells display alterations affecting NF-κB, JAK/STAT, and PI3K/AKT pathways, facilitated by somatic mutations, chromosomal gains, and epigenetic remodeling that silence B-cell-defining genes. Despite reprogramming, clonality and somatic hypermutation patterns confirm their origin from germinal center B-cells, even in EBV-associated cases. Collectively, the morphology, phenotype, and genotype of HRS cells reveal a complex pathogenic network in which intrinsic oncogenic pathways and extrinsic TME interactions co-operate to sustain malignant transformation. Understanding these integrated mechanisms provides a biological foundation for current therapeutic strategies. Full article

Background: Oncocytic lipoadenoma is an exceptionally rare benign fat-containing salivary gland tumor that most commonly arises in the parotid gland. Previous case reports have largely focused on histopathology with limited or single-modality imaging documentation; therefore, practical preoperative radiological characterization remains challenging. Case Presentation: A 46-year-old male presented with a 2-year history of a slowly enlarging right-sided parotid mass. Computed tomography and magnetic resonance imaging showed a well-circumscribed fat-containing mass with a discrete medially enhancing solid component, mild diffusion restriction and small cystic foci without aggressive features. Ultrasonography revealed a heterogeneously hypoechoic parotid mass; however, limited acoustic penetration hindered evaluation of the deep portion. A core-needle biopsy was inconclusive, and an atypical lipomatous tumor could not be excluded. Subsequent surgical excision confirmed an oncocytic lipoadenoma, a biphasic tumor comprising mature adipose tissue and cytokeratin 7-positive oncocytic epithelial nests. The patient has remained recurrence-free for 7 years after surgery. Conclusions: Fat-containing parotid tumors can be diagnostically challenging because imaging findings are often nonspecific, and biphasic lipoepithelial entities are rarely encountered. This case highlights that awareness of the pattern of macroscopic fat with a discrete enhancing non-fat component, interpreted alongside histopathological findings, may help narrow the differential diagnosis, guide management, and reduce diagnostic uncertainty. Full article

Background/Objectives: Imaging of both cardiac sympathetic denervation and nigrostriatal dopaminergic degeneration can support the diagnosis of Parkinson’s disease (PD). However, their temporal relationship and combined diagnostic value remain unclear. This review addresses (1) whether nigrostriatal degeneration and cardiac sympathetic denervation are correlated in PD and (2) the comparative and combined diagnostic accuracy of striatal dopaminergic and cardiac sympathetic imaging in PD. Methods: We searched PubMed (October 2025) for studies assessing both a striatal dopaminergic and a cardiac sympathetic imaging biomarker in the same PD cohort, supplemented by citation chaining. Diagnostic accuracy studies were evaluated using QUADAS-2. Results: Nineteen studies met the inclusion criteria. Ten studies examined within-subject associations; six reported significant correlations ranging from weak to strong (ρ ~0.2–0.8). Two studies observed a significant correlation for the akinetic-rigid subtype but not for the tremor-dominant subtype of PD. Ten studies compared diagnostic accuracies, five of which used pre-defined thresholds and consistently found higher sensitivity for [¹²³I]FP-CIT SPECT (78–100%) compared to [¹²³I]MIBG scintigraphy (65–82%), but higher specificity for [¹²³I]MIBG (range 75–100%) than for [¹²³I]FP-CIT (range 11–73%). Adding [¹²³I]MIBG scintigraphy to [¹²³I]FP-CIT SPECT generally increased specificity but had inconsistent effects on overall accuracy. QUADAS-2 revealed substantial risks of patient selection bias, data-driven thresholds, and limited blinding. Conclusions: Reported correlations between nigrostriatal dopaminergic degeneration and cardiac sympathetic denervation in PD are inconsistent, likely reflecting both methodological heterogeneity and real variation between phenotypes. There may be a stronger correlation in the akinetic-rigid phenotype. Dopaminergic imaging is more sensitive in early PD, while cardiac sympathetic imaging is more specific for differentiating PD from atypical Parkinsonian syndromes. However, study designs greatly restrict the generalizability of reported diagnostic accuracies. Full article

Background: Germline CDKN2A variants are associated with Familial Atypical Mole-Malignant Melanoma (FAMMM) syndrome. This syndrome involves an increased risk of melanoma, pancreatic cancer, and, in specific populations, duodenal cancer, breast cancer, and astrocytoma. The CDKN2A (c.146T>C) variant has been found in hereditary cancer patients within the Mexican population. Furthermore, the phenotype linked to this variant in Mexico differs from that observed in other groups. This study aims to evaluate the founder effect of the CDKN2A (c.146T>C) variant through epidemiological analysis and to describe the phenotype within our population. Patients and Methods: We examined 72 Mexican patients (14 probands from distinct families, 48 relatives, and 10 nonrelated probands) carrying the CDKN2A (c.146T>C) form three hereditary cancer centers between September 2023 and September 2025. Results: Of the 72 individuals analyzed, 52 (72.22%) tested positive. A cancer diagnosis was established in 27 (37.50%) of the individuals analyzed. Breast cancer was the most common neoplasia, accounting for 19 cases (70.37%), followed by melanoma with 4 cases (14.81%) and ovarian cancer with 2 cases (7.40%). Three patients (11.11%) had two distinct primary neoplasms. Conclusions: Based on our findings and the fact that this variant has been reported nearly exclusively in the Mexican population, we conclude that it has a founder effect in this population. Additionally, the phenotype associated with this variant can vary among populations, with breast cancer being the most common carcinoma rather than melanoma among Mexican carriers, highlighting the importance of updating screening guidelines. Full article

Accurate short-term load forecasting at disaggregated levels is critical for energy management in microgrids and institutional environments, yet it remains a challenge due to high consumption variability and limited contextual information. This paper proposes a hybrid model that combines Fuzzy ARTMAP neural networks with K-means clustering to improve hourly load forecasting using real data from a university microgrid. The methodology includes key preprocessing steps such as filtering low-load records, removing holidays, interpolating missing values, and applying cyclic encoding to standardize the data into 96 time intervals per day (15-min resolution). For each prediction, the average load profile of the five most recent weekdays is computed and compared to cluster centroids to identify the most similar group, which is then used to train the neural network. Results demonstrate consistent improvements in MAPE, RMSE, and MAE compared to the non-clustered baseline. The model showed robustness to non-stationary behavior and atypical patterns, even when relying solely on timestamp and load data. The proposed strategy outperformed conventional approaches and proved suitable for complex, data-limited environments. Full article

General pustular psoriasis (GPP) is a rare, potentially life-threatening neutrophilic dermatosis. Pediatric cases are uncommon and often misdiagnosed due to overlapping clinical and histopathological features with other pustular dermatoses. We present a case of an 11-year-old boy, initially diagnosed with Sneddon–Wilkinson syndrome, who presented with disseminated pustular eruptions, with no response to antibiotics, dapsone, and glucocorticosteroids. In histopathology, we observed subcorneal neutrophilic pustules. Due to atypical features and poor treatment response, the patient underwent genetic testing, which revealed a homozygous IL36RN gene c.338C>T (p.Ser113Leu) pathogenic variant, which enabled a definitive diagnosis of GPP. Treatment with acitretin led to clinical improvement. Pediatric GPP poses diagnostic and treatment challenges. Genetic testing for IL36RN pathogenic variants may aid in the diagnosis, especially in atypical cases. The presence of the biallelic IL36RN pathogenic variant supports the diagnosis of DITRA (Deficiency of the IL-36 Receptor Antagonist, ORPHA:404546)—a monogenic autoinflammatory form of GPP. Full article

Background: Acute transverse myelitis (ATM) is an inflammatory disorder of the spinal cord with heterogeneous etiologies, including autoimmune, infectious, paraneoplastic, and drug-induced causes. Tumor necrosis factor-alpha (TNF-α) inhibitors have been infrequently associated with inflammatory central nervous system events, including transverse myelitis. TNF-inhibitor-associated myelitis typically presents with short-segment lesions, a normal brain MRI, and partial responsiveness to corticosteroids. Longitudinally extensive transverse myelitis (LETM) and steroid-refractory cases are uncommon. Case Presentation: A 39-year-old woman with psoriatic arthritis treated with etanercept for two years presented with subacute progressive bilateral lower-extremity sensory loss and weakness. MRI revealed a T2 hyperintense spinal cord lesion extending from T11 to L1 with gadolinium enhancement, consistent with transverse myelitis, while brain MRI was normal. Cerebrospinal fluid analysis showed lymphocytic pleocytosis, elevated protein, oligoclonal bands, and increased kappa free light chains. Extensive infectious, metabolic, paraneoplastic, and autoimmune testing, including aquaporin-4 and MOG antibodies, was negative. Despite high-dose intravenous corticosteroids and the discontinuation of etanercept, the patient experienced clinical worsening with lesion expansion, meeting criteria for LETM, and developed urinary retention. She subsequently underwent plasma exchange, resulting in radiologic improvement and moderate clinical recovery. Conclusions: This case highlights an atypical presentation of TNF-inhibitor-associated myelitis characterized by a biphasic course, longitudinally extensive spinal cord involvement, steroid refractoriness, and responsiveness to plasma exchange. These features suggest either an unusually severe TNF-inhibitor-related inflammatory phenotype or a TNF-inhibitor-triggered antibody-mediated demyelinating process. Reports of TNF-inhibitor-associated myelitis evolving into longitudinally extensive, steroid-refractory disease remain limited, and this presentation may broaden the recognized clinical spectrum of TNF-α-related CNS inflammatory events. Close neurologic follow-up and heightened awareness of severe CNS complications associated with TNF-α inhibitors are warranted. Full article

Background/Objective: Sarcomatoid squamous cell carcinoma (sSCC) is a rare tumor that resembles atypical fibroxanthoma/pleomorphic dermal sarcoma (AFX/PDS) and spindle cell/dedifferentiated melanoma histologically. Methods: Immunohistochemistry was performed on 51 sSCCs from 46 patients, 26 AFX/PDS from 24 patients, and 15 spindle cell/dedifferentiated melanoma from 15 patients. Twenty-nine studies comprising 307 sSCCs, 636 AFX/PDS, and 168 spindle cell/dedifferentiated melanomas were included in the pooled analysis. Results: p63 showed the highest pooled sensitivity for sSCC (0.89), followed by keratin AE1/AE3 (0.87), keratin MNF116 (0.87), keratin 903 (0.85), p40 (0.82), and keratin 5/6 (0.72). Evidence regarding pooled diagnostic performance was limited for several markers. Among the best-supported markers for sSCC, p63 demonstrated a pooled OR of 42.36 (95% CI 13.95–128.61), sensitivity of 0.82, and specificity of 0.94; p40 showed a pooled OR of 50.27 (95% CI 13.91–181.70), sensitivity of 0.90, and specificity of 0.85; and keratin 5/6 had a pooled OR of 108.60 (95% CI 27.10–435.20), sensitivity of 0.94, and specificity of 0.93. For AFX/PDS, CD10 showed a pooled OR of 10.64 (95% CI 2.96–38.19), sensitivity of 0.73, and specificity of 0.80. For spindle cell/dedifferentiated melanoma, S100 showed a pooled OR of 161.23 (95% CI 24.55–1058.69), sensitivity of 0.95, and specificity of 0.94 (95% CI 0.85–0.97), while SOX10 yielded a pooled OR of 121.27 (95% CI 6.33–2323.34). Conclusions: A panel comprising p63 or p40, keratin 5/6, CD10, CD163 or CD68, and SOX10 or S100 may aid in distinguishing sSCC from AFX/PDS and spindle cell/dedifferentiated melanoma. Full article

Background and Clinical Significance: Dupuytren’s disease (DD) typically affects the palmar fascia and proximal digital structures, with distal interphalangeal joint (DIPJ) involvement considered rare. True extension of DD into the volar pulp has not been previously documented. Distal lesions may be misdiagnosed as neoplastic or inflammatory masses, and optimal management of isolated distal cords remains uncertain. We present the first histologically confirmed case of DD extending beyond the DIPJ into the volar pulp, accompanied by a systematic review of reported DIPJ-dominant DD. Case Presentation: A 30-year-old right-hand-dominant male presented with a two-year history of progressive flexion deformity of the little finger. Examination demonstrated a 90° proximal interphalangeal joint and 55° DIPJ contracture. Ultrasound and MRI showed a well-circumscribed soft-tissue lesion along the radial middle phalanx but did not suggest DD. Open exploration via an ulnar digital approach revealed a discrete DD cord extending distally beyond the DIPJ into the volar pulp, closely associated with the ulnar neurovascular bundle. Limited fasciectomy achieved full correction without neurovascular compromise. Histopathology confirmed classic DD. At the twelve-month follow-up, the patient maintained full extension and function with no recurrence. Conclusions: This study reports the first confirmed case of DD extending into the volar pulp and highlights that atypical distal DD can occur even in young patients. Imaging may fail to identify DD in uncommon sites, reinforcing the importance of clinical suspicion. Limited fasciectomy remains safe and effective in the distal phalanx. Recognition of this phenotype or histopathological examination may improve diagnostic accuracy and guide tailored operative planning. Full article

Granuloma annulare is a non-infectious granulomatous dermatosis with a probable pathogenic mechanism of delayed-type hypersensitivity, in which the dermal histiocytic granulomatous infiltrate is usually accompanied by a lesser component of lymphocytes. Although there are more common clinical and histopathological patterns of presentation, there are less well-known variants that may pose significant diagnostic challenges by mimicking other inflammatory cutaneous processes or even neoplastic conditions. One of the rarest forms of granuloma annulare is the pseudolymphomatous variant, in which the lymphocytic component is not only highly prominent but may, in some cases, partially or completely obscure the histiocytic component itself. This feature, together with the fact that the clinical presentation of this variant is often atypical—frequently lacking the characteristic annular morphology of conventional granuloma annulare—renders the diagnosis particularly challenging. From an immunohistochemical standpoint, the infiltrates described are predominantly composed of T cells, with only a sparse and scattered B-cell component. In this article, we present a case of granuloma annulare with a pseudolymphomatous B-cell component (PAX5⁺, CD79⁺) and minimal T-cell involvement, observed in a 4 mm skin nodule located on the shoulder of a 48-year-old male. This case therefore broadens the concept of pseudolymphomatous granuloma annulare to include infiltrates predominantly composed of B lymphocytes. Full article

Ventricular repolarization abnormalities are among the most frequent electrocardiographic findings in pediatric athletes undergoing cardiovascular screening, yet their clinical significance remains a major source of diagnostic uncertainty. While most of them represent benign expressions of training-induced cardiac remodeling and developmental maturation, selected patterns may constitute the earliest phenotypic manifestation of cardiomyopathies or primary electrical disease. Distinguishing physiological adaptation from early pathology is therefore essential to prevent both sudden cardiac events and unnecessary restrictions on sports participation. This review integrates contemporary international electrocardiographic interpretation criteria with emerging pediatric evidence to provide a clinically oriented framework for evaluation and risk stratification of ventricular repolarization abnormalities in pediatric athletes. Early repolarization and anterior T-wave inversion are commonly benign when occurring within recognized age- and ethnicity-specific patterns and in the absence of symptoms, concerning family history, or structural abnormalities. Conversely, lateral or inferolateral T-wave inversion, atypical ST-segment morphology, complex ventricular arrhythmias, and abnormal imaging findings represent red flags requiring comprehensive investigation, including multimodality imaging when indicated. Due to the dynamic electrophysiological evolution during adolescence, longitudinal reassessment is crucial. A structured, risk-based approach integrating electrocardiographic features, demographic/familial context, clinical evaluation, imaging findings, and follow-up provides a pragmatic strategy to optimize risk detection while safeguarding appropriate athletic participation in young athletes. Full article

Imitation is crucial for social learning, yet children with autism spectrum disorder (ASD) often show atypical imitation abilities. To probe the neural dynamics that precede overt imitation, electroencephalography (EEG)—with a focus on α (8–12 Hz) and β (13–30 Hz) activity commonly linked to action observation and sensorimotor processing—was used to index pre-imitation processing in preschool-aged children with ASD. Grounded in the social motivation framework, this study combined an EEG experiment and a naturalistic behavioral intervention. In Study 1, 11 preschool children with ASD completed an action-observation (pre-imitation) task under low- versus high-sociality video conditions. Time–frequency and spectral analyses were conducted to compare α- and β-band responses across conditions. In Study 2, four children received a six-week Reciprocal Imitation Training (RIT) program, and imitation and social-communication outcomes were assessed pre-, mid-, and post-intervention. The results showed that low-sociality stimuli elicited stronger frontal and prefrontal power increases in both α and β bands, whereas high-sociality stimuli elicited more temporally dynamic β-band responses but with lower overall power engagement. Although inferential support was limited by sample size, behavioral trends suggested improvements following RIT in imitation and related social functioning, with larger gains in children with mild-to-moderate ASD. Together, these findings suggest that social context modulates pre-imitation neural activity in ASD and that socially grounded imitation training may support broader social development. Full article

Atypical visual attention to aversive or threatening stimuli is a clinically relevant feature of aggressive behavior. However, the developmental dissociation between sustained visual allocation and early orienting remains unclear. This study examined the temporal dynamics of visual attentional biases in a sample of 119 children and adolescents (51 males, 68 females), clinically and behaviorally categorized into aggressive and non-aggressive cohorts. Using a free-viewing paradigm with standardized emotional stimulus pairs selected from the International Affective Picture System (IAPS), eye-tracking analysis focused on first-fixation direction and dwell time. Inferential analyses were conducted using Linear Mixed-Effect Models (LMM) and Generalized Linear Mixed-Effects Models (GLMM). The linear model revealed a significant main effect of behavioral condition: individuals with aggressive traits, regardless of their stage of development, showed greater sustained visual allocation toward negative stimuli. In contrast, the GLMM for first-fixation direction identified a significant age-by-condition interaction, indicating that early orienting differences were more clearly expressed in the aggressive adolescent cohort. These findings suggest that sustained visual preference for negative content may represent a relatively stable correlate of aggressive traits, whereas early orienting differences may vary across developmental stages. Together, these two temporal eye-tracking measures may provide complementary information for future computational approaches to aggression screening. In conclusion, these two temporal oculomotor dimensions may provide a useful feature space for future machine-learning pipelines and may serve as complementary candidate markers for comparing computational predictions against clinically established ground truth in aggression screening research. Full article

Background/Objectives: Colorectal cancer (CRC) is a leading cause of cancer-related mortality worldwide. Emerging evidence highlights the role of the gut microbiota in the development and progression of CRC. Microbial dysbiosis is hypothesized to contribute to chronic inflammation through a variety of mechanisms, such as the production of free radicals, which induce mutagenesis and immune dysregulation in the host, ultimately leading to diseases such as cancer. Methods: Tumor tissue samples or healthy mucosa tissue were collected for bacterial DNA extraction. The V3–V4 region of the 16S rRNA gene was amplified and sequenced using the Illumina MiSeq platform. Bioinformatics analysis was performed with QIIME2, including quality control, DADA2 denoising, alpha and beta diversity calculation, and taxonomic classification using the SILVA database. Results: Differences in microbial composition were observed between groups. The healthy controls exhibited high relative abundances of beneficial genera such as Faecalibacterium, Bacteroides, and Asteroleplasma, whereas the patients with CRC showed enrichment of atypical genera including Novosphingobium, Bradyrhizobium, and Undibacterium. Alpha diversity was lower in the CRC group, and clear clustering by group was observed in the beta diversity analysis. LEfSe analysis identified potential bacterial biomarkers associated with CRC at both the species and genus levels. Conclusions: The findings of this study support the hypothesis that colorectal cancer is associated with distinct alterations in gut microbiota composition, such as an increase in the Novosphingobium genus and a decrease in the Bacteroides genus. An exploratory description of these microbial profiles may aid in the development of microbiome-based diagnostic and therapeutic strategies and contribute to current knowledge of the role of the gut microbiota in CRC in southern Peru. Full article