Search Results (10,265)

Parathyroid carcinoma (PC) is a rare endocrine malignancy characterized by aggressive clinical behavior driven primarily by parathyroid hormone (PTH) overproduction. Standard morphological assessments frequently struggle to definitively distinguish true carcinomas from atypical benign lesions, presenting significant diagnostic challenges and a risk of overdiagnosis. Recent advances emphasize the genetic and epigenetic foundations of PC tumor biology. A central oncogenic mechanism involves the CDC73 gene, where the biallelic inactivation of CDC73 and the gain of function of mutant parafibromin—which destabilizes p53 mRNA—facilitate apoptosis evasion. Additionally, alterations in parallel pathways, such as the PI3K/AKT/mTOR cascade, and epigenetic dysregulation further contribute to disease progression. To address morphological limitations, contemporary diagnostic approaches increasingly utilize adjunctive multimarker immunohistochemical panels (including parafibromin, Ki-67, and Galectin-3) and explore emerging non-coding RNA liquid biopsy signatures. Finally, this review discusses the development of preclinical models and the application of genotype-guided targeted therapies, aiming to improve the clinical management and precision medicine strategies for PC. Full article

Background and Clinical Significance: Bicuspid aortic valve (BAV) is the most common congenital heart defect and may coexist with other cardiovascular anomalies. Among these is a single coronary artery (SCA), a rare congenital condition in which the entire coronary circulation originates from a single coronary ostium. Cardiac computed tomography (CCT) enables simultaneous evaluation of coronary artery anatomy and aortic valve morphology with high spatial resolution, which may influence procedural strategy in patients undergoing valve interventions. Case Presentation: This report represents the first documented case of a 59-year-old male with mixed aortic valve disease in whom preoperative CCT revealed the coexistence of BAV, SCA (Lipton type L-I), and myocardial bridging (MB) involving the mid segment of the left anterior descending artery (LAD). Identification of these findings was crucial for preoperative assessment and contributed to the selection of an appropriate surgical strategy. Conclusions: CCT plays a key role in the preoperative evaluation of valvular heart disease, including in patients with coexisting BAV and SCA. It enables individualized procedural planning and minimizes the risk of perioperative complications. Full article

BK and JC Polyomaviruses (BKPyV and JCPyV) are ubiquitous human pathogens capable of establishing lifelong, asymptomatic persistence in the majority of the global population. While decades of research have focused on their lytic replication cycles and the development of severe diseases, such as polyomavirus-associated nephropathy (PVAN) caused by BKPyV and progressive multifocal leukoencephalopathy (PML) caused by JCPyV, their primary evolutionary strategy is one of persistence rather than pathogenesis. This review shifts the perspective from a replication-centric framework towards an evolutionary persistence model, detailing the multi-layered host and viral determinants that maintain the homeostatic balance. At the cellular level, viral genomes are restricted by chromatinization into minichromosomes and host S-phase licensing. These constraints are reinforced by innate immune sensing and adaptive T-cell and antibody responses that curtail systemic dissemination while permitting periodic, low-level urinary shedding, which is essential for horizontal transmission. In addition to these host barriers, the viruses utilize intrinsic regulatory mechanisms to prevent excessive replication and immune detection, including the stable archetype non-coding control region (NCCR), viral microRNAs that downregulate early gene expression, and the small t antigen (STAg). Finally, we address unresolved questions regarding the full spectrum of cellular reservoirs, the molecular triggers of reactivation, and the ecological factors shaping their transmission routes. Understanding these maintenance mechanisms is crucial for refining clinical interventions and managing the rare, devastating transitions from silent persistence to lytic disease. Full article

Background/Objectives: Alzheimer’s disease (AD) is a progressive neurodegenerative disorder for which MRI-based AI systems are increasingly used for diagnosis and prognosis. However, many published approaches remain misaligned with the requirements of trustworthy clinical use. Predicted risks are often poorly calibrated, explanations are frequently limited or non-actionable, guideline-aligned reporting is uncommon, and longitudinal prediction is inconsistently evaluated. In this paper, we conduct a PRISMA-guided structured review with scoping-style breadth of MRI-centric AI methods for AD diagnosis. This design supports a theme-based synthesis across heterogeneous study designs and is intended to summarize the current evidence base and derive practical design requirements for next-generation, clinically oriented pipelines that integrate calibrated staging, explainable outputs, and longitudinal risk modeling. Methods: Searches were conducted across Scopus, PubMed/PMC, and arXiv/bioRxiv (2014–2026; English; human AD/MCI imaging) and were supplemented by backward and forward snowballing. These searches yielded 2460 records. After deduplication, screening, and full-text eligibility assessment, 90 papers were included in the final synthesis. The included literature was organized into thematic streams spanning counterfactual reasoning and explainable AI (XAI), vision–language approaches for report and caption generation, longitudinal and survival-style modeling, and multimodal fusion and transformer-based methods combining MRI with clinical variables and other biomarkers. Vision–language methods were considered together with retrieval-augmented paradigms. Results: Key findings are that the field has shifted toward transformer architectures and multimodal fusion and shows increased interest in richer explanation mechanisms. Nevertheless, calibration metrics and robustness checks are inconsistently reported, external site-held-out validation and subgroup analyses remain relatively uncommon, and guideline-aligned structured reporting with explicit numeric provenance is rare. Vision–language and retrieval-augmented reporting methods are far more mature in general radiology than in AD MRI, highlighting a translational opportunity. Conclusions: Based on these findings, we recommend standardized reporting of classification calibration and longitudinal risk calibration, stronger site-held-out validation with subgroup robustness evaluation, clinically meaningful counterfactuals, and guideline-aligned reporting with reproducible numeric provenance embedded within reproducible pipelines. Full article

Background/Objectives: Sacral giant cell tumor of bone (GCTB) is a rare, mostly benign but locally aggressive neoplasm that carries significant diagnostic and treatment challenges due to its anatomic complexity, proximity to sacral nerve roots as well as the blood vessels, and potential impact on bowel, bladder, sexual, and lumbopelvic function and stability. This narrative review aimed to synthesize current evidence on the epidemiology, clinical presentation, diagnostic evaluation, classification, management strategies, outcomes, and surveillance of sacral GCTB. Methods: A focused literature search of PubMed/MEDLINE and Google Scholar was conducted for studies published between January 2000 and January 2026, with additional manual review of reference lists. Given the rarity of the tumor and the observed heterogeneity in study designs, treatment strategies, and outcomes, the evidence was synthesized narratively. Results: Sacral GCTB mainly affects young adults with an indolent nature, often presenting late with progressive low back or buttock pain, radiculopathy, or neurological deficits. Magnetic resonance imaging is the preferred modality for determining local extent, whereas histopathologic biopsy and molecular testing remain essential for definitive diagnosis. Conventional grading systems, such as Enneking and Campanacci, have limited value in sacral disease, as anatomical extent and anticipated neurological morbidity are more relevant for treatment planning. Surgery remains the cornerstone for resectable disease, yet management plans should balance local tumor control against preservation of sacral nerve roots and mechanical stability. Denosumab, selective arterial embolization, and radiotherapy may play important roles in selected unresectable or high-morbidity cases. Local recurrence remains a major concern, and long-term surveillance is recommended because tumor relapse, treatment-related morbidity, and distant metastasis may occur late. Conclusions: Current evidence supports a multidisciplinary, individualized approach to sacral GCTB, guided by tumor extent, expected neurological morbidity, and patient-centered functional outcomes. Prospective multicenter studies are needed to refine treatment algorithms and improve risk stratification. Full article

Background: Pulmonary actinomycosis is a rare chronic infection that frequently mimics lung malignancy, often leading to delayed diagnosis due to its non-specific clinical and radiological presentation. Given the diagnostic challenges associated with this condition, the aim of this study was to evaluate the clinical presentation, diagnostic pathways, treatment strategies, and outcomes of patients diagnosed with pulmonary actinomycosis in a single center. Methods: We retrospectively reviewed patients diagnosed with pulmonary actinomycosis at our institution between January 2014 and December 2022. Diagnosis was established based on compatible clinical and radiological findings together with microbiological identification of Actinomyces by culture or polymerase chain reaction. Results: Twenty-two patients were included in the final analysis. The median age was 61.5 years and males were more frequently affected (59%). The median time from initial hospitalization to definitive diagnosis was 70 days. Actinomyces odontolyticus was the most frequently identified species. All patients received antibiotic therapy, with a median treatment duration of 45.5 days. Thirteen patients underwent surgical intervention, performed either for diagnostic purposes or for treatment of complications. Complete disease eradication through surgical management was achieved in six cases. During follow-up (median 24 months), overall survival at three years was 78%, with one death directly related to pulmonary actinomycosis. Conclusions: Pulmonary actinomycosis remains a diagnostic challenge due to its non-specific clinical presentation and low microbiological yield. Early clinical suspicion and a combined diagnostic approach including bronchoscopy and microbiological testing are essential for timely diagnosis. Surgical intervention may play an important diagnostic and therapeutic role in selected patients. Full article

Background: Pregnancy following liver and kidney transplantation is rare. The presence of a rare genetic disorder and advanced chronic kidney disease (CKD) further complicates clinical management, for which evidence-based guidelines are limited. Case presentation: A 29-year-old woman with Alagille syndrome underwent combined liver and kidney transplantation in early childhood. She had stage 4 CKD, and her baseline creatinine was around 250 umol/L. Her pregnancy was unplanned and diagnosed at 19+1 weeks of gestation. After the diagnosis of pregnancy, immunosuppressive therapy was promptly adjusted, and potentially teratogenic medications were discontinued. At 21+1 weeks’ gestation, creatinine and urea levels rose despite multidisciplinary management, and she started renal replacement therapy. Despite ongoing multidisciplinary care, the pregnancy was complicated by placental abruption at 24+5 weeks, requiring a preterm cesarean section. A live-born female infant weighing 590 g was delivered. Discussion: The coexistence of CKD, long-term immunosuppression, and high obstetric risk requires early multidisciplinary assessment and individualized management. Currently, standardized protocols for monitoring and treatment are lacking in this rare population, making clinical decision-making particularly challenging, especially regarding CKD progression. Conclusion: Pregnancy in women with combined liver and kidney transplantation and advanced CKD carries a high risk of severe renal and obstetric complications. Preconception counseling and early referral to multidisciplinary teams may help improve management in similar rare clinical scenarios. Full article

Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal malignancy, with rising incidence and a 5-year survival rate of 13%. Late presentation, early metastasis, and intrinsic resistance constrain the efficacy of cytotoxic chemotherapy, which remains the backbone of PDAC treatment, with only modest survival gains and resistance nearly universal. Although KRAS mutations dominate tumour biology (~90% of cases), PDAC is a heterogeneous disease with distinct molecular subtypes that confer differential therapeutic vulnerabilities. Advances in comprehensive molecular profiling have catalysed a paradigm shift toward precision oncology in PDAC. In KRAS-mutant PDAC, mutation-specific inhibitors have established proof-of-concept, particularly in KRAS G12C disease, while next-generation approaches including KRAS G12D inhibitors, RAS-“ON” inhibitors, proteolysis-targeting chimeras (PROTACs), and KRAS-targeted vaccine strategies are expanding the therapeutic landscape. Combination strategies targeting upstream and downstream effectors of the RAS–MAPK pathway are also being explored to enhance the depth and durability of response. In parallel, KRAS-wild-type PDAC has emerged as a molecularly distinct subgroup enriched for rare but actionable alternative oncogenic fusion drivers including NRG1, NTRK, RET, ALK, and FGFR. Additional molecularly directed strategies targeting HER2 alterations, BRAF mutations, EGFR-dependent signalling, and tumour-selectively exposed surface antigens such as CLDN18.2 are under investigation across PDAC irrespective of KRAS mutation status. Synthetic lethal approaches, including targeting the PRMT5/CDKN2A/MTAP axis, represent a further emerging therapeutic strategy. Germline homologous recombination repair defects, particularly involving BRCA1/2 and PALB2, further define clinically important subsets with sensitivity to platinum chemotherapy and PARP inhibition. This review summarises current and emerging targeted and molecularly directed therapeutic strategies in PDAC, emphasising the importance of molecular stratification and recent advances shaping precision oncology in this historically treatment-refractory disease. Full article

Ring finger protein 43 (RNF43) encodes a transmembrane E3 ubiquitin ligase that negatively regulates canonical Wnt signaling and is classically associated with serrated polyposis syndrome and colorectal cancer. In this study, regarding a homozygous truncating RNF43 variant (NM_001305545.1:c.1906C>T; p.Gln636Ter) in a patient segregating with a severe neurodevelopmental phenotype characterized by developmental delay, neonatal hypotonia, recurrent seizures, progressive microcephaly, and bilateral optic atrophy, the loss of polarity defective 1 (plr-1), an ortholog of RNF43, was modeled in Caenorhabditis elegans and the phenotype was primarily characterized. The results demonstrated that loss of the plr-1 disrupted gamma aminobutyric acid (GABA)ergic axon organization, reduced locomotor speed calculated from 60 s recordings, and altered developmental growth. These findings expand the phenotypic spectrum of RNF43 and support a dosage-dependent developmental role. Full article

Introduction: Post-infectious bronchiolitis obliterans (PIBO) is a rare and severe chronic lung disease. Our goal was to characterize respiratory epithelium in children with PIBO, which remains unexplored, using an ex vivo model culture. Methods: Proximal bronchial biopsies from children with PIBO and reconstituted bronchial epithelium from PIBO patients (n = 3) and controls (n = 17) were analyzed using an air–liquid interface culture model. Epithelial cell composition, barrier integrity, and mediator production, including mucins, inflammatory and antiviral responses, were assessed in this pathological and functional approach. Results: Epithelial thickness was assessed in PIBO biopsies. Ex vivo reconstituted PIBO epithelia appeared to exhibit comparable cohesion and cell composition to controls. Mucin expression and secretion were likewise similar between groups. PIBO epithelial might have displayed reduced IL-33 transcript levels and decreased TSLP secretion, whereas IFN-λ1, IFN-λ2-3 and IFN-β secretion could have been elevated. No differences were detected in remodeling markers (MMP-9 and YKL-40). Conclusions: In summary, ex vivo model of PIBO epithelia suggested that the epithelium may preserve structural characteristics and mucin production, without evidence of remodeling. However, PIBO epithelial cells may have a distinct immune profile, with lower alarmin expression and higher interferon secretion. This could indicate a tendency toward enhanced antiviral response rather than structural changes. These preliminary results need to be confirmed in larger cohorts. Full article

Background and Clinical Significance: NMDAR autoimmune encephalitis is a rare but potentially life-threatening autoimmune disorder that can be hard to recognize initially because it has nonspecific symptoms. In the early phase of the disease, clinical presentation is often dominated by psychiatric symptoms, which can be misleading. A diagnosis is established by demonstrating specific anti-NMDA receptor antibodies, with cerebrospinal fluid analysis considered the most reliable diagnostic method. Timely initiation of immunomodulatory therapy, including corticosteroids, intravenous immunoglobulins, and therapeutic plasmapheresis, significantly improves disease outcomes, while second-line therapies are used in refractory cases. Case Presentation: A 21-year-old female patient (M.B.) was admitted to the Psychiatry Clinic at the University Clinical Center of Vojvodina due to the sudden onset of behavioral changes, including social withdrawal, absence of verbal communication, and unusual orofacial grimacing. During hospitalization, the patient was intermittently in a state of severe psychomotor agitation and poorly communicative, with pronounced orofacial dyskinesias and involuntary tongue movements. Anti-NMDA receptor autoantibodies were detected in both serum and cerebrospinal fluid, and the patient was subsequently transferred to the Intensive Care Unit of the Neurology Clinic. Due to the lack of an adequate clinical response to pulse corticosteroid therapy, six cycles of therapeutic plasmapheresis were performed. Following this treatment, significant clinical improvement was observed. Conclusions: Timely recognition of this condition and a multidisciplinary approach allow for early initiation of immunomodulatory therapy and significantly improve treatment outcomes. Full article

Background and Objectives: Primary myelofibrosis (PMF) is a rare hematologic malignancy with non-specific symptoms, causing diagnostic delays and missed diagnoses. Automated screening in heterogeneous electronic health records (EHRs) is challenging due to class imbalance, data sparsity, and incomplete labeling. We investigated two complementary objectives: (1) developing a screening algorithm using routine EHR data to identify PMF-risk patients for hematology consultation, and (2) assessing the applicability of positive-unlabeled (PU) learning. Methods: Using EHR data from 10 Polish hospitals, we evaluated several ensemble models and found that LightGBM achieved the best performance. Results: LightGBM achieved AP 20.83% (95% CI: 19.18–24.35%), sensitivity 45.52% (95% CI: 39.48–52.72%), and precision 14.72% (95% CI: 13.80–17.01%)—substantially exceeding expected prevalence (over 340-fold enrichment). The model captured interactions among RDW and PLT parameters revealing high-risk unlabeled patients with confirmed diagnoses (n = 5) or clinical profiles resembling PMF cases (n = 31), confirming PU problem. Conclusions: Although PU methods enhanced sensitivity, they reduced precision to levels exceeding real-world healthcare capacity. Ensemble learning enables disease identification in clinical settings. Full article

Esophagopulmonary fistula (EPF) with lung abscess is a rare but serious complication during neoadjuvant chemoradiotherapy (nCRT) for esophageal squamous cell carcinoma and is often associated with poor prognosis. We report a 52-year-old man with cT3N3M0 esophageal squamous cell carcinoma who developed fever and hemoptysis during the third week of nCRT. Computed tomography showed a newly developed right lower lobe lung abscess adjacent to the primary tumor, suspicious for esophageal perforation with fistulous communication. Because the lesion and infection appeared localized, staged aggressive surgery was undertaken. The patient underwent en bloc esophagectomy and right lower lobectomy with cervical esophagostomy, followed by delayed reconstruction using a laparoscopically created gastric conduit. Final pathology showed marked treatment response with ypT1bN0 disease, and the resected lung showed no malignant involvement. R0 resection was achieved, and the patient remains disease-free at 28 months. This case illustrates a possible management pathway in a highly selected patient with localized EPF and lung abscess during nCRT, suggesting that early staged source control may preserve reconstructive options when systemic deterioration has not yet occurred. Full article

Rift Valley fever (RVF) is a viral zoonosis endemic in Madagascar, threatening human and animal health as well as the economy. Trade-related livestock movements are a major factor in the spread of RVF virus. While previous RVF research in Madagascar has focused on farmers or general ecology, this study is the first to specifically target livestock traders, the primary drivers for long-distance viral spread, in the Alaotra Mangoro endemic hotspot. This study aimed to assess the level of knowledge, prevailing attitudes and current practices regarding RVF among people engaged in livestock trade in the Alaotra Mangoro region, as well as the factors associated with these KAPs. A descriptive and analytical cross-sectional survey was conducted among 406 livestock traders in five districts of the Alaotra Mangoro region, using a structured questionnaire. A multi-stage sampling approach was employed, utilising purposive selection of markets followed by snowball sampling to reach informal traders often missed by traditional surveys. Generalised linear mixed models were used to analyse factors associated with KAPs regarding RVF. Awareness of RVF was very low (only 18.5% respondents had heard of it), with significant regional disparities (0% in Anosibe An’Ala versus 51.6% in Moramanga). Veterinarians (15.5%), family (12.8%), radio (9.6%) and neighbours (9.6%) were the main sources of information. Understanding of symptoms and modes of transmission (particularly mosquito bites) was limited. Higher levels of education (OR = 181.6; 95% CI: 29.9–1123.7; p < 0.001) and older age (50–60 years) were associated with better knowledge. Proactive attitudes were scarce (21.4%), although more than half (53.4%) believed that RVF is a real disease. Perception of personal risk and the contribution of livestock trade to the spread of the disease was low. However, confidence in animal vaccination was relatively high (60.3%). Preventive practices were highly inadequate. The majority did not wear protective equipment when handling sick animals (94.6%) and rarely avoided touching aborted foetuses (12.6%). Less than half (48.3%) expressed a willingness to report sick or dead animals, and nearly half admitted to having sold or purchased sick livestock (49.5%). Cooking meat (95.1%) and using mosquito nets (74.1%) were the only well-established practices. More than half of respondents (57.9%) lived more than 5 km from veterinary services, and cost was the most frequently cited barrier to consultation. Participation in awareness campaigns was virtually non-existent (5.4%). Results revealed critical gaps in KAP that may contribute to the persistence of RVF. A “One Health” approach is imperative, integrating human, animal and environmental health. Full article

Neurodegenerative diseases are among the most consequential disorders of later life, not only because of their increasing prevalence, rising from approximately 1–2% at age 65 to over 30% by age 85, but also because they develop within the broader clinical context of ageing, multimorbidity, frailty, and polypharmacy. In older adults, these conditions rarely present as isolated and static diagnostic entities; rather, they unfold as dynamic clinical trajectories involving the progressive interaction of cognitive decline, behavioural-neuropsychiatric symptoms, and extrapyramidal-motor dysfunction. In this review, we propose a trajectory-based framework for the interpretation and management of major neurodegenerative disorders in later life, including Alzheimer’s disease, frontotemporal dementia, Parkinson’s disease and Parkinson’s disease dementia, dementia with Lewy bodies, and vascular cognitive impairment. Building on a conceptual model organized around three major symptom spheres: cognitive, behavioural-neuropsychiatric, and extrapyramidal-motor, we argue that each disorder can be understood according to the relative predominance and temporal evolution of these domains. Alzheimer’s disease is typically cognition-led, frontotemporal dementia behaviour-led, and Parkinsonian syndromes motor-led, whereas dementia with Lewy bodies shows early multidomain convergence across all three spheres simultaneously. Vascular and mixed dementias follow more heterogeneous trajectories shaped by lesion burden, network disruption, and copathology. This framework has direct implications for diagnosis, prognostic stratification, and treatment selection, because interventions targeting one sphere may destabilize another and generate prescription cascades, delirium, or functional decline. We further discuss how biomarker-based diagnosis, disease-modifying therapies, non-pharmacological interventions, multidisciplinary care, deprescribing strategies, and palliative planning can be integrated within a trajectory-based approach. Interpreting neurodegeneration through clinical trajectories rather than diagnostic labels alone offers a more realistic and therapeutically useful model for precision geriatric neurology across the full course of disease. Full article