Search Results (8,909)

Background: Tularemia is a rarely identified disease in Slovenia. In summer 2024, we detected a tularemia outbreak in the Kranjsko-Sorško polje, located in North-Western part of Slovenia. Aim: To describe the epidemiological investigations and preventive measures to contain the outbreak. Methods: The patients with confirmed tularemia were interviewed. Serology and PCR was used for microbiological confirmation of tularemia and in some patients by isolation from blood or by RT-PCR. Results: The majority of confirmed tularemia cases in 2024 were infected in the geographically limited area in North-Western part of Slovenia (38/46). Tularemia was confirmed in two patients by isolation Francisella tularensis subsp. holarctica from blood or wound, in one by blood PCR, and in the others by serology. Most cases were associated with mowing or harvesting hay with intensive dusting. Twenty-eight (75.7%) out of 37 cases developed pulmonary tularemia. Sixteen cases were hospitalized. After confirming the outbreak, we alerted medical professionals in the region and the general public using the regional and national media and website of National Institute of Public Health. Conclusions: Endemic tularemia in Slovenia is associated with handling wild life and presents in ulceroglandular form. In the localized outbreak in year 2024 there was an extraordinary upsurge of pulmonary tularemia, with many of the cases initially investigated for lung cancer based on the radiology reports. Due to dry weather condition in summer 2024, excessive dusting associated with mowing the grass and handling hay resulted in inhalation of infective aerosols leading to the infection with F. tularensis. Full article

Multiple myeloma (MM) is a complex genetic disease characterized by the heterogeneity of tumor cells. We have measured KRAS, NRAS, and BRAF gene mutations in circulating free tumor DNA (ctDNA) from plasma, bone marrow, and plasmacytoma samples as well as their correlation with various clinical and laboratory parameters. The prospective study included 113 MM patients (74 with plasmacytoma and 39 without), treated at the National Medical Research Center for Hematology (Moscow, Russia) from 2009 to 2024. FISH was performed on CD138+ bone marrow cells for 104 patients and array-CGH for two extramedullary plasmacytoma samples. Mutation analysis on CD138+ bone marrow cells was performed for 99 patients, on ctDNA for 80 patients, and, in 26 cases, samples of plasmacytoma were also investigated. Mutations in the KRAS, NRAS, and BRAF genes either in bone marrow, ctDNA, or plasmacytoma samples were found in 50% of patients. In patients with plasmacytoma, mutations in ctDNA were found in 28% of cases versus 0% in cases without plasmacytoma (p = 0.0007). Rare “noncanonical” KRAS and NRAS gene mutations were also more frequent in ctDNA compared to the bone marrow substrate (50% versus 9%, p = 0.01). Liquid biopsy in MM, particularly identification of the KRAS, NRAS, and BRAF gene mutations in ctDNA, is a valuable instrument for prognostication. Researching the intricate mechanisms underlying extramedullary involvement, and identifying novel high-risk factors associated with the disease, is worthwhile. Full article

Background/Objectives: Recent state-of-the-art advances in deep learning have significantly improved diagnostic accuracy in medical imaging, particularly in chest radiograph (CXR) analysis. Motivated by these developments, a comprehensive comparison was conducted to investigate how architectural choices affect performance of 14 deep learning models across Convolutional Neural Networks (CNNs), Transformer-based models, and Mamba-based State Space Models. Methods: These models were trained and evaluated under identical conditions on the NIH ChestX-ray14 dataset, a large-scale and widely used benchmark comprising 112,120 labeled CXR images with 14 thoracic disease categories. Results: It was found that recent hybrid architectures—particularly ConvFormer, CaFormer, and EfficientNet—deliver superior performance in both common and rare pathologies. ConvFormer achieved the highest mean AUROC of 0.841 when averaged across all 14 thoracic disease classes, closely followed by EfficientNet and CaFormer. Notably, AUROC scores of 0.94 for hernia, 0.91 for cardiomegaly, and 0.88 for edema and effusion were achieved by the proposed models, surpassing previously reported benchmarks.Conclusions: These results not only highlight the continued strength of CNNs but also demonstrate the growing potential of Transformer-based architectures in medical image analysis. This work contributes to the literature by providing a unified, state-of-the-art benchmarking of diverse deep learning models, offering valuable guidance for researchers and practitioners developing clinically robust AI systems for radiology. Full article

Background: Gastrointestinal neuroectodermal tumour (GNET), also known as clear cell sarcoma (CCS) of the gastrointestinal tract, is a rare neural crest-derived malignancy characterized by EWSR1-ATF1 or EWSR1-CREB1 fusions. Due to its rarity, there is limited evidence and no established guidelines for standard management. GNET is aggressive, with high rates of local recurrence, metastasis, and mortality. Case Presentation: We report the case of a 46-year-old woman with a family history of gastrointestinal cancers who was diagnosed in 2020 with an intestinal GNET. She underwent a segmental enterectomy as the first step of multimodal therapy. After three years of follow-up, she developed hepatic and peritoneal metastases. In November 2023, she began combined therapy with the anti-VEGF tyrosine kinase inhibitor cabozantinib and the immune checkpoint inhibitor nivolumab. The patient has maintained stable disease for 18 months with good tolerance and no adverse events. Molecular analysis of the tumour, which showed an EWSR1-CREB1 fusion, supported the selection of targeted therapy and immunotherapy as the preferred treatment approach. Conclusions: Immunotherapy and targeted therapy show promise for GNET/CCS treatment, but clinical standards are lacking, and evidence comes primarily from case reports. Additional data are needed to determine the best sequence and combination of therapies for this very rare disease. Full article

Background: Artificial intelligence (AI) is increasingly applied in the diagnosis of pediatric rare diseases, enhancing the speed, accuracy, and accessibility of genetic interpretation. These advances support the ongoing shift toward personalized medicine in clinical genetics. Objective: This review examines current applications of AI in pediatric rare disease diagnostics, with a particular focus on real-world data integration and implications for individualized care. Methods: A narrative review was conducted covering AI tools for variant prioritization, phenotype–genotype correlations, large language models (LLMs), and ethical considerations. The literature was identified through PubMed, Scopus, and Web of Science up to July 2025, with priority given to studies published in the last seven years. Results: AI platforms provide support for genomic interpretation, particularly within structured diagnostic workflows. Tools integrating Human Phenotype Ontology (HPO)-based inputs and LLMs facilitate phenotype matching and enable reverse phenotyping. The use of real-world data enhances the applicability of AI in complex and heterogeneous clinical scenarios. However, major challenges persist, including data standardization, model interpretability, workflow integration, and algorithmic bias. Conclusions: AI has the potential to advance earlier and more personalized diagnostics for children with rare diseases. Achieving this requires multidisciplinary collaboration and careful attention to clinical, technical, and ethical considerations. Full article

Objective: Sinonasal squamous cell carcinoma (SNSCC) is a rare and aggressive malignancy, with limited treatment strategies in the recurrent or metastatic cases. Although immune checkpoint inhibitors (ICIs) have shown efficacy in head and neck cancers (HNCs), clinical data specific to SNSCC are scarce. This study aimed to evaluate the therapeutic efficacy and prognosis of ICIs in patients with SNSCC. Methods: We conducted a retrospective review of 18 patients with pathologically confirmed SNSCC treated with nivolumab or pembrolizumab at Gifu University Hospital between May 2017 and December 2024. Treatment response was assessed using RECIST v1.1 criteria. Overall response rate (ORR) and disease control rate (DCR) were evaluated as treatment effects, and overall survival (OS) and progression-free survival (PFS) were evaluated as prognoses. Subgroup analyses were performed according to treatment regimen. Results: The ORR and DCR for all patients were 43.8% and 56.3%, respectively. Pembrolizumab-treated patients showed higher response rates (ORR: 66.7%; DCR: 83.3%) compared to those treated with nivolumab (ORR: 30%; DCR: 40%). Median OS and PFS were 21.5 and 7.9 months, respectively. Long-term durable responses exceeding two years were observed in several cases. Although pembrolizumab tended to result in better outcomes, no statistically significant difference was found between groups. Immune-related adverse events were infrequent and manageable. Conclusions: This study suggests that a subset of patients with SNSCC may benefit from ICI therapy, particularly in combination with chemotherapy. Despite the rarity of SNSCC, accumulating clinical evidence—including prospective studies—is essential to establish standardized treatment strategies for this disease. Full article

Background and Clinical Significance: Acquired angioedema (AAE) is a rare and potentially life-threatening condition characterized by acquired deficiency of C1-inhibitor (C1-INH) resulting in hyperactivation of the classical complement pathway. AAE occurs in association with malignancies or autoimmune diseases. Infectious triggers are rarely encountered, and the underlying mechanisms have yet to be completely clarified. Case Presentation: This case involves a previously healthy 19-year-old male who was admitted with Mycoplasma pneumonia and oral ulcers, subsequently developing unilateral facial angioedema. Laboratory studies demonstrated reduced C4, decreased levels and activity of C1-INH, and reduced C1q, all consistent with acquired C1-INH deficiency. These findings were attributed to the presence of cold agglutinins, which are frequently observed in Mycoplasma pneumoniae infections. Following treatment with icatibant, a bradykinin B2 receptor antagonist, the patient’s angioedema resolved rapidly. An exhaustive workup found no evidence of underlying systemic disorders, and the patient did not experience any angioedema attacks following resolution of the infection. Conclusions: The presence of cold agglutinins, commonly associated with Mycoplasma infections, can precipitate a decline in C1-INH levels, resulting in complement pathway dysregulation. This disruption leads to an excess of bradykinin, followed by increased vascular permeability and localized edema. Full article

Objective: Fabry disease (FD) is a rare, X-linked lysosomal storage disorder resulting from deficient α-galactosidase A activity, which can manifest as left ventricular hypertrophy (LVH). We aimed to assess the prevalence of FD in an unselected cohort of patients with unexplained LVH. Methods and results: We screened 202 unrelated adults with LVH using enzymatic assays for α-galactosidase A in dried blood spots. Patients with low activity underwent GLA gene sequencing. Echocardiographic parameters were evaluated according to ESC guidelines. FD was diagnosed in 4 women (2%), each carrying distinct pathogenic GLA mutations. All affected individuals showed normal or borderline enzyme activity. Cardiac, renal, or neurological symptoms were observed variably among patients. Echocardiographic findings revealed slightly lower wall thickness and preserved systolic function in FD patients compared to those without FD. Cascade genetic screening identified 16 additional family members with the same mutations. One patient (0.5%) was incidentally diagnosed with Gaucher disease based on syndromic features and enzymatic testing. Conclusions: FD was identified in 2% of patients with unexplained LVH, who were females. Enzyme-based screening followed by targeted genetic testing is a cost-effective strategy for FD detection. Early diagnosis is essential for prompt treatment and family counselling, underscoring the importance of routine FD screening in patients with LVH of unclear aetiology. Our findings support the use of targeted screening for Fabry disease in patients with LVH and systemic features, and highlight the potential to identify other lysosomal disorders in selected cases. Full article

Background and Clinical Significance: Triosephosphate isomerase (TPI) deficiency is a rare autosomal recessive metabolic disorder caused by a pathogenic variant in the TPI1 gene. It is characterised by chronic haemolytic anaemia, progressive neuromuscular dysfunction, and reduced life expectancy. Patients typically present with symptoms in the first few months of life, including muscle weakness, ataxia, and recurrent respiratory infections. Diagnosis is confirmed by genetic testing, and management is generally symptomatic as no treatment is available. Case Presentation: We describe the case of an infant diagnosed with TPI deficiency in the context of haemolytic anaemia with progressive neurological deterioration and respiratory failure. Conclusions: This case illustrates the complexity of the disease and highlights the importance of early diagnosis and contributes to the limited literature by providing a detailed clinical description and highlighting the diagnostic challenges associated with this condition. Beyond its clinical relevance, this report emphasises the potential role of personalised medicine in the management of TPI deficiency. Early identification of specific genotypes may inform prognosis and guide individualised supportive strategies. As knowledge of the molecular underpinnings of TPI deficiency expands, opportunities may emerge for targeted therapeutic approaches tailored to patient-specific characteristics. Full article

Sarcocystosis is a parasitic infection caused by obligate intracellular coccidia, which infect humans, domestic animals, and wildlife. More than 200 Sarcocystis species have already been identified, but for many of these, the life cycle, pathogenesis, and clinical signs remain unclear. The infection is cosmopolitan, with high prevalence in cattle herds worldwide. Although the clinical disease in definitive hosts is considered rare, the high number of sporocysts released by them drives the incidence in production animals. Furthermore, sarcocystosis has some One Health relevance due to its zoonotic potential, especially concerning species infecting primates. Few studies have reported on the epidemiology of sarcocystosis in Brazil. However, a high prevalence of the disease was found in areas where investigations of Sarcocystis species were conducted, which highlights the potential for foodborne transmission to humans. Therefore, it is relevant to study this parasitic disease so that control and prophylaxis measures can be adopted. This study aims to review the current state of knowledge on Sarcocystis spp. in farm animals in Brazil. Full article

Background: This study was aimed to comprehensively investigate the clinical and molecular characteristics, treatments, and outcomes of young patients with lung cancer in the new era of cancer treatment. Methods: Clinical data from patients aged 18 to 45 with lung cancer, treated at our hospital from January 2014 through January 2024, were systematically collected and analyzed. Results: This study enrolled a total of 343 patients, with a predominance of females, never-smokers, and those diagnosed at an advanced stage. Adenocarcinoma was the most common histology (72.0%), and rare tumors could also be seen in young patients, such as pulmonary sarcomatoid carcinoma and pulmonary mucoepidermoid carcinoma. The mutation rate of the epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) in NSCLC patients were 35.9% (111/309) and 14.2% (44/309), respectively. PD-L1 expression was assessed in 55 patients, with 14 showing high expression (≥50%) and 24 showing negative expression (<1%). The median overall survival (mOS) for the entire cohort was 80.2 months, with a 5-year survival rate of 55.7%. For patients with stage I, II, and III disease, the mOS had not yet been reached, whereas the mOS for stage IV patients was 39.7 months. Targeted therapy, particularly second-generation ALK tyrosine kinase inhibitors (TKIs), significantly improved the prognosis of patients with driver gene mutations. Chemotherapy combined with immunotherapy was beneficial for patients with progressive disease or driver gene negativity in NSCLC and was associated with improved OS in small cell lung cancer (SCLC). Female, family history of lung cancer, positive driver genes, and first-line use of second-generation ALK-TKIs are independent prognostic factors in young patients with advanced NSCLC. Conclusions: Our findings highlight the importance of early diagnosis, targeted therapy, and immunotherapy in improving outcomes for young patients with lung cancer. Full article

Objectives: Patients with rare diseases in China face extremely high medical expenses. The current coverage framework remains inadequate in terms of coverage depth and proactive risk control, underscoring an urgent need for institutional reform. Methods: This study employs a policy content analysis approach to review the current landscape of rare disease protection in China. Drawing on risk management theory and the health capital model, it constructs an analytical framework to examine potential institutional reforms through the lens of risk response pathways and the efficiency of health investment. Results: The findings reveal that basic medical insurance (BMI) provides limited financial protection for patients with rare diseases. Among China’s 31 provincial-level administrative centers, 24 have set general outpatient reimbursement ceilings under the urban and rural resident basic medical insurance (URRBMI) at 1000 RMB or less. In comparison, 24 cities have set outpatient reimbursement limits under the urban employee basic medical insurance (UEBMI) at 6000 RMB or less. The security system relies predominantly on the BMI, while supplementary mechanisms have failed to provide effective support or continuity in coverage. Current policies are generally reactive, with coverage typically triggered only after a confirmed diagnosis and often lacking early intervention or preventive strategies. Conclusions: China’s rare disease security system urgently requires structural improvements in coverage depth and proactive risk management. The proposed Dedicated Insurance Scheme for Rare Diseases (DISRD) presents a feasible and sustainable model for China’s multi-tiered system of securing rare diseases. It provides valuable institutional insights for other countries and regions seeking to build public health systems with proactive risk control capabilities. Full article

Background: Calciphylaxis (calcific uremic arteriolopathy), is a rare disease characterized by subcutaneous vascular thrombosis and necrotic skin lesions, which mainly affects patients with kidney disease. This condition often has a poor prognosis, unclear pathophysiology, and lacks standardized treatment. Case Description: We present a case of calciphylaxis in a 53-year-old female patient who reported gradually worsening unbearable pain in her lower limbs and thighs, persisting for approximately 18 months. After appropriate examinations and biopsy of non-healing wounds, histopathology confirmed the diagnosis of calciphylaxis. The wounds were treated with dermo-epidermal (DE) grafts. Followingly, the patient underwent treatment in a hyperbaric chamber, after which the wounds decreased in size. Conclusions: Early diagnosis and a comprehensive approach to therapy are necessary to improve the management of calcification, a rare disease, and complications such as non-healing wounds. Full article

Skin metastases represent a rare finding in dermatological practice, but their presence signifies an advanced disease and usually portends a poor prognosis. They commonly arise as multiple painless nodules in patients with a cancer history. Differential diagnoses are challenging, and zosteriform metastases should not be mistaken for herpes zoster. Dermoscopy typically reveals a white, structureless pattern. A skin biopsy with routine hematoxylin–eosin staining is essential for an accurate diagnosis, while immunohistochemistry is particularly useful in cases of anaplastic tumors. Breast cancer is the most common cause of skin metastasis in women, and lung cancer is the most common in men. The life expectancy after diagnosis is generally low. Cutaneous metastasectomy, electrochemotherapy, and radiotherapy are generally regarded as beneficial for palliative purposes. Intralesional cryosurgery was found to be beneficial in a few case series. Systemic immunotherapy can induce the regression of cutaneous metastases in selected patients. Full article

Background: Pregnancy and lactation-associated osteoporosis is a rare cause of severe skeletal fragility in young women typically presenting with vertebral compression fractures during late pregnancy or postpartum. Its rarity and lack of risk factors often delay diagnosis. Case presentation: The patient was a 34-year-old pregnant Italian woman, presenting with severe osteoporosis related to pregnancy and lactation. The patient presented for the first time at the Outpatient clinic of the Rehabilitation Unit in the Department of Public Health at the University of Federico II, Naples in March 2024, exhibiting severe symptoms indicative of osteoporosis, along with acute lower back pain. During the anamnesis, it was revealed that the patient was unable to bend forward, with reduced flexion and extension movements. The symptoms began during the third trimester. Management and diagnosis: In terms of diagnosis, clinical exams were conducted to confirm the disease. The MRI exam showed fractures and vertebral variations, with significant findings including calcification. Additionally, DXA indicated lower values compared to normal Treatment included: breastfeeding cessation, correction of calcium and vitamin D deficiencies, and bisphosphonate injection therapy. It is noteworthy that the rehabilitative approach has been recommended throughout pharmacological treatment and especially upon its suspension. Ultimately, the primary cause of this condition was pregnancy as bone resorption increases during pregnancy. Outcome: Following clodronate treatment completion, the patient showed full clinical recovery and significant radiological improvement. Follow-up DXA one year after diagnosis revealed normalized bone density and the patient had gained autonomy in activities of daily living with no further symptoms. Full article