Search Results (7,986)

Background: Salivary gland cancers (SGCs) are a rare and heterogeneous group of malignancies, accounting for approximately 5% of head and neck cancers. Despite their rarity, advances in molecular profiling have revealed a variety of genetic and molecular pathways, many of which are potentially actionable with targeted therapies. Methods: We reviewed the current literature involving the molecular landscape of SGCs, encompassing the diagnostic and prognostic value of tissue and liquid biomarkers and the potential therapeutic targets across various histological subtypes. Results: Our review highlights key molecular diagnostic findings such as the CRTC1-MAML2 fusion in mucoepidermoid carcinoma and MYB-NFIB rearrangements in adenoid cystic carcinoma, but also targetable alterations such as HER2 and AR positivity in salivary duct carcinoma and ETV6-NTRK3 fusion in secretory carcinoma. Liquid biopsy (both blood- or salivary-based), including circulating tumor DNA, circulating tumor cells, and miRNAs, offers novel, noninvasive approaches for disease monitoring and personalized treatment. Emerging therapies such as HER2 inhibitors, androgen deprivation therapy, and TRK inhibitors underscore the shift towards precision oncology in managing these malignancies. Conclusions: Despite promising advances, challenges remain due to the rarity and phenotypic heterogeneity of SGCs, emphasizing the need for molecularly stratified clinical trials. This review presents an overview of tissue and liquid biomarkers, focusing on molecular targets and therapeutic innovations that lay the foundation for improved diagnostic and treatment strategies for SGCs. Full article

Spinal cord infarction (SCI) of arterial origin is a rare vascular event, and its incidence is probably underestimated. There are no strong epidemiological data, and the diagnostic pathway is complex and sometimes incomplete. Furthermore, many cases may be misdiagnosed as other forms of acute and subacute myelopathies. The focus of this review is the clinical and neuroradiological issues in diagnosing SCI and their respective reliability in a clinical setting. The new proposed diagnostic criteria of SCI, although not covering all aspects, highlight the need for a comprehensive approach, including even atypical cases, as the lack of cord compression on Magnetic Resonance Imaging (MRI) is the only mandatory feature for diagnosis. Some MRI features are supportive of the diagnosis, particularly when the anterior spinal artery territory is involved and diffusion-weighted imaging (DWI) is used. Several etiologies can be considered, considering traditional vascular risk factors and diseases affecting the aorta and its main branches, yet a significant proportion of cases remain without a definite etiology. The strongest predictor of SCI diagnosis is a clinical variable, i.e., a time to nadir of severe deficits < 12 h. Full article

Background/Objectives: Ulcerative colitis (UC) and Crohn’s disease (CD) are the usual clinical forms of inflammatory bowel disease (IBD). Changes in the oral microbiota, especially the presence of emerging fungi and herpesviruses, have been shown to worsen the clinical aspects of IBD. The aim of this study was to screen for emerging pathogens in the oral yeast microbiota and the presence of herpesvirus in IBD patients. Methods: Oral swabs of seven UC or CD patients were collected. The samples were plated on Sabouraud Dextrose Agar and subcultured on CHROMagar Candida and CHROMagar Candida Plus. Polyphasic taxonomy was applied and identified using molecular tools, such as MALDI-TOF MS and ITS partial sequencing. Multiplex qPCR was used to identify the herpesvirus. Results: The mean age was 38.67 ± 14.06 years, 57.14% were female, and two had diabetes. The CD patients presented with Rhodotorula mucilaginosa, Candida orthopsilosis and Kodamaea jinghongensis, while the UC patients presented with Cutaneotrichosporon dermatis, Candida glabrata, Candida lusitanea and Candida tropicalis. Two UC individuals had at least one herpesvirus. In the first individual, a co-detection of Herpes Simplex Virus 1 (HSV-1) and C. lusitaniae was observed. The second presented with co-infections of Epstein–Barr virus (EBV), Human Herpesvirus 7 (HHV-7) and C. tropicalis. Conclusions: We identified rarely described yeasts and co-infections in IBD patients, highlighting the need to identify emerging pathogens in the oral microbiota, as they may contribute to opportunistic infections. Full article

Endogenous Cushing’s syndrome (CS) is a rare neuroendocrine disorder characterized by either secondary cortisol increases due to an adrenocorticotropic hormone (ACTH)-secreting pituitary tumor (Cushing’s disease (CD)), an ACTH-secreting neuroendocrine tumor (NET) of non-pituitary origin (ectopic ACTH syndrome (EAS)), or by the primarily adrenal autonomous overproduction of cortisol [...] Full article

Background: Sickle cell disease (SCD) is a rare autosomal recessive disorder that is common in countries with consanguineous marriages. It leads to various complications, including painful episodes, infections, delayed growth, stroke, and organ damage, which contribute to high healthcare utilization and costs. In Saudi Arabia, the prevalence of SCD is notably high, largely due to the frequency of consanguineous marriages. However, there has not yet been a study estimating the direct medical costs of managing SCD based on real-world data. This study aims to assess these costs in Saudi Arabia. Methods: Data were collected from electronic medical records (EMRs) at a university-affiliated tertiary care center. A micro-costing approach was used to estimate the direct medical costs (e.g., laboratory tests, imaging, emergency department visits, hospitalizations, prescription medications, outpatient visits, etc.) retrospectively over a 12-month follow-up period. The baseline characteristics of the patients were presented using frequencies and percentages. The costs of different healthcare services were analyzed using means and the 95% confidence intervals. A generalized linear model (GLM) with a gamma distribution was utilized to examine the association between the overall costs and patient characteristics (e.g., age, gender, duration of illness, surgeries, blood transfusions, etc.), allowing for the estimation of the adjusted mean costs. Results: A total of 100 patients met the inclusion criteria and were included in the analysis. The mean age of the patients was 10.21 years (±6.87 years); 53% were male, and a substantial majority (96%) had the HbSS genotype. Sixty-one percent of the patients had undergone at least one red blood cell (RBC) exchange transfusion, while 21% had undergone surgical procedures, including tonsillectomy, splenectomy, and cholecystectomy. Additionally, 45% had experienced at least one vaso-occlusive crisis (VOC), and 59% had been hospitalized at least once in the past 12 months. Factors such as the frequency of laboratory tests and imaging studies, the length of hospital stay (LOS), the rate of emergency department (ED) visits, surgical procedures, the number of prescription medications, and the frequency of blood transfusions were all significant predictors of higher direct medical costs (p < 0.05). The estimated mean annual direct medical costs per patient were USD 26,626.45 (95% CI: USD 22,716.89–USD 30,536.00). After adjusting for various factors, including age, gender, duration of illness, frequency of lab and imaging tests, LOS, ED visits, surgical procedures, number of prescription medications, rates of VOCs, and RBC exchange transfusions, the adjusted mean annual direct medical cost per patient was calculated to be USD 14,604.72 (95% CI: USD 10,943.49–USD 19,525.96). Conclusions: The results of this study emphasize the substantial direct medical costs linked to sickle cell disease (SCD), which are greatly affected by the frequency of related complications. These insights should motivate policymakers and healthcare researchers to assess both the national direct and indirect costs associated with SCD, especially given the significant number of SCD patients in Saudi Arabia. Full article

Cutaneous angiosarcoma is a rare and aggressive malignant tumor that originates from the endothelial cells of blood vessels or lymphatic vessels. More than half of cutaneous angiosarcoma cases occur in the head and neck regions, particularly on the scalp. However, due to its rarity, scalp angiosarcoma is often overlooked in clinical practice. The lack of distinctive symptoms usually delays the diagnosis and, implicitly, the initiation of appropriate treatment. The treatment of cutaneous angiosarcoma poses great challenges due to its multifocal occurrence and the frequent extensive microscopic spread. A personalized, multimodal therapeutic approach is essential for ensuring a favorable outcome, consisting of a wide surgical excision associated with adjuvant radiotherapy in localized tumors, concurrent adjuvant radiotherapy and chemotherapy, targeted treatments, or immunotherapy in advanced or metastatic diseases. The aim of this manuscript is to review the literature data regarding the individualized management of cutaneous angiosarcoma and to share our own experiences in the field. We wish to underscore the importance of considering cutaneous angiosarcoma in the differential diagnosis of scalp tumors, especially in patients with a history of scalp irradiation as early detection, accurate diagnosis, and a multidisciplinary, personalized management, including surgery with clear margins and adjuvant radiation therapy, are crucial for ensuring a favorable outcome. Full article

Multiple myeloma (MM) is a complex and heterogeneous hematologic malignancy characterized by clonal evolution, genetic instability, and interactions with a supportive tumor microenvironment. These factors contribute to treatment resistance, disease progression, and significant variability in clinical outcomes among patients. This review explores the mechanisms underlying MM progression, including the genetic and epigenetic changes that drive clonal evolution, the role of the bone marrow microenvironment in supporting tumor growth and immune evasion, and the impact of genomic instability. We highlight the critical insights gained from single-cell technologies, such as single-cell transcriptomics, genomics, and multiomics, which have enabled a detailed understanding of MM heterogeneity at the cellular level, facilitating the identification of rare cell populations and mechanisms of drug resistance. Despite the promise of advanced technologies, MM remains an incurable disease and challenges remain in their clinical application, including high costs, data complexity, and the need for standardized bioinformatics and ethical considerations. This review emphasizes the importance of continued research and collaboration to address these challenges, ultimately aiming to enhance personalized treatment strategies and improve patient outcomes in MM. Full article

Congenital diaphragmatic hernia (CDH) is a relatively rare and severe developmental disease. Even with the most recent multidisciplinary therapies, the risk for neonatal mortality and morbidity remains high. Recent advancements in prenatal treatments, alongside experimental and clinical data, suggest that fetoscopic endoluminal tracheal occlusion (FETO) promotes lung development and offers a promising strategy against lung hypoplasia and pulmonary hypertension. It is the only existing direct mechanical therapy that intervenes in the regulation of pulmonary pressure. Its influence on lung development also interferes with tissue homeostasis and cell differentiation; it also enhances inflammation and apoptosis. Its physiopathology on cellular and molecular levels is still poorly understood. Unfortunately, the procedure also carries significant pregnancy-, maternal-, and fetus-related risks. Assessing a multifaceted intervention requires a collective view of all aspects. This scoping review uncovers potential materno-fetal procedure-related risks and highlights innovative solutions. Future research on lung development therapies in CDH may focus on the “dual hit” mechanism, combining molecular-targeting drugs and regenerative medicine with the mechanical nature of FETO for synergistic effects. Full article

Background and Clinical Significance: Mucopolysaccharidosis type VII (MPS VII), an ultrarare lysosomal storage disorder caused by β-glucuronidase deficiency, presents significant therapeutic challenges. Given its extreme rarity and limited treatment experience in Asian populations, documenting long-term treatment outcomes is crucial for advancing clinical knowledge and improving patient care. Case Presentation: We report a 3-year follow-up of enzyme replacement therapy (ERT) in the first Taiwanese case of MPS VII. The patient, who initially presented with hydrops fetalis and developmental delay, was diagnosed at age 4 through genetic analysis, which revealed compound heterozygous variants of c.104C > A (p.Ser35Ter) and c.1454C > T (p.Ser485Phe) on the GUSB gene. ERT with vestronidase alfa was initiated at age 6. During the follow-up period, significant clinical improvements were observed, including elimination of oxygen dependency, with BiPAP needed only during sleep; changes in mobility, with 6-min walk test distance showing an initial decline from 130 to 70 m followed by partial recovery to 95 m after multiple orthopedic surgeries; and steady progression of growth parameters showed, with height increasing from 110 to 118 cm. Urinary glycosaminoglycan (GAG) levels measured by dimethylmethylene blue spectrophotometry decreased and stabilized. The patient’s cardiac and hepatic conditions remained stable, although splenomegaly persisted. No severe adverse events were reported during ERT. Conclusions: This case demonstrates the effectiveness and safety of long-term ERT in MPS VII, particularly in improving respiratory function and physical performance. Our experience highlights the importance of early diagnosis and treatment initiation, while providing valuable insights into the management of this ultrarare disease in the Asian population. Full article

Marek’s disease (MD), characterized by the rapid onset of T-cell lymphomas in chickens, is caused by Mardivirus gallidalpha2, an oncogenic alphaherpesvirus commonly known as Marek’s disease virus (MDV). MDV encodes a bZIP protein, Meq, which contains a bZIP domain (basic DNA-binding and leucine zipper dimerization domain) at the amino terminus and a transcriptional regulatory domain at the carboxyl end. Meq can transform murine and chicken fibroblasts in vitro and is essential for tumor formation in chickens. Meq homodimerization and heterodimerization through its bZIP domain are involved in Meq-mediated transformation. However, the role of Meq DNA-binding and transcriptional regulatory domains in transformation has not been investigated. In this study, we constructed recombinant Md5 (very virulent MDV) viruses expressing chimeric Meq proteins generated by swapping the DNA-binding and transcriptional regulatory domains of Meq of Md5 and vaccine (CVI988/Rispens) strains. Our results show that these recombinant viruses, rMd5-Md5/CVI-Meq (Md5 DNA-binding domain and CVI transcriptional regulatory domain) and rMd5-CVI/Md5-Meq (CVI DNA-binding domain and Md5 transcriptional regulatory domain), replicated at levels similar to parental rMd5 in cell culture and chickens and could transmit efficiently among chickens. Interestingly, parental rMd5 and chimeric viruses exhibited distinct pathogenic phenotypes in chickens: rMd5 caused 100% mortality, a moderate level of tumor incidence in visceral organs and small visceral tumors; rMd5-Md5/CVI-Meq caused 100% mortality, a high level of tumor incidence in visceral organs, and very large visceral tumors; while rMd5-CVI/Md5-Meq caused an average of 37% mortality, rarely induced tumors in visceral organs, and the visceral tumors were small. In conclusion, our study suggests that the DNA-binding domain of Meq plays an essential role in transformation (tumor incidence), while the transcriptional regulatory domain of Meq influences the distribution and size of MDV-induced tumors. Full article

Among the most concerning threats impacting global forest ecosystems is the pinewood nematode (Bursaphelenchus xylophilus (Steiner and Buhrer, 1934) Nickle, 1970), the causal agent of pine wilt disease. In Europe, effective management of this pest requires comprehensive regulatory and monitoring strategies, including the annual collection of thousands of wood samples from symptomatic trees and their surroundings, inspection of wood packaging materials like pallets, and the trapping of the insect vector, Monochamus spp., through national networks. Insects and wood samples are sent to official laboratories, where the latter are sometimes incubated at 25 °C for 15 days, aiming to maximize the probability of the detection of the nematode. This study expected to elucidate the effect of the wood incubation process on the detection of B. xylophilus by analyzing wood samples from pallets and green wood obtained from pine stands, both harbouring nematodes in adult and juvenile stages. Additionally, the investigation sought to assess how the presence of fungi, which serve as a food source for the nematodes, enables B. xylophilus to persist in treated pallet wood that is colonized by these fungi. The results indicated that the incubation period is unnecessary for detecting B. xylophilus in pallets, except when the wood is heavily colonized by fungi providing suitable nutrition for the nematodes, although such occurrences are expected to be rare. Furthermore, this study found no significant differences in population growth between the two stages of the nematode’s life cycle. This suggests that second-stage juveniles present in wood samples, despite not undergoing sexual differentiation, do not hinder the reproductive capacity of B. xylophilus. The risk of a potential infestation in treated pallet wood is unlikely if the treatment has been performed correctly, and the incubation does not contribute to increasing the probability of detecting the PWN. Conversely, for samples obtained from trees, the incubation period significantly enhances nematode detection. Full article

Background/Objectives: Uterine carcinosarcoma (UCS) refers to a rare high-grade aggressive epithelial non-endometrioid endometrial carcinoma, with tumour cells demonstrating epithelial–mesenchymal metaplastic transition and composed of both carcinomatous epithelial and sarcomatous (homologous or heterologous) components. Methods: The aim of this study was to evaluate the epidemiology, management approach, outcomes and survival patterns of patients with UCS. Seventy-seven cases of UCS treated with primary surgery in a single tertiary centre underwent retrospective cohort analysis across a ten-year period. Observational data on clinicopathological variables and treatment pathways were reviewed and independent risk factors for relapse and mortality were analysed. Results: The 5-year disease-free and overall survival rates were 52.10% and 46.6%, respectively. Cervical stromal involvement was independently related to disease-free survival (HR = 6.26; 95%CI 1.82–21.59; p = 0.004) and overall survival (HR = 3.64; 95%CI 1.42–9.38; p = 0.007), whilst sarcomatous component type was independently related to recurrence only (HR = 3.62; 95%CI 1.38–9.51; p = 0.009) after adjusting for other pathological and treatment variables. No significant difference in recurrence or mortality was found when comparing the performance of pelvic lymph node dissection (p = 0.803 and p = 0.192 respectively) or the administration of adjuvant treatment (p = 0.546 and p = 0.627 respectively). Conclusions: Whilst our data suggests an encouraging similarity in overall survival rates compared with the literature, UCS continues to represent significant treatment challenges—with a paucity of guidelines available. Data regarding molecular analysis was not systemically available in our cohort, the more recent introduction of which (alongside the revision of endometrial cancer staging) will undoubtedly provide UCS patients with improved therapeutic options in the future. Full article

Background: Madelung’s disease is a rare lipid metabolic disorder characterized by diffuse and symmetrical adipose tissue deposits in the subcutaneous fascial spaces, presenting with multiple painless masses throughout the body. The disease is more common in middle-aged adults with a history of chronic alcohol consumption. Case Report: This article reports a case of Madelung’s disease from Romania in a 67-year-old man admitted to our department for multiple adipose masses located in the neck and upper back. MRI examination of the head and neck revealed symmetrical and non-encapsulated fat deposition. Surgical intervention was performed to resect the adipose masses. The article also discusses the etiology, clinical manifestations, diagnosis, and surgical treatment of large adipose lesions. Conclusions: This case report provides insights for the diagnosis and treatment of Madelung’s syndrome. Full article

Introduction: Primary colorectal lymphoma (PCL) is a very rare disease with limited information regarding its macroscopic features. This retrospective descriptive study aims to identify the macroscopic characteristics of PCL and explore treatment trends and outcomes with respect to histopathologic subtypes. Methods: This IRB-approved study from a large academic medical center identified 66 patients with colorectal lymphoma from 1998 to 2022 from a tumor registry. Thirty-four patients met the inclusion criteria of having PCL with available endoscopic data. The macroscopic features of each lesion were identified. Treatment trends and outcomes were examined at the patient level. Data were described using frequency and percentages for categorical characteristics and the median and interquatile range (IQR) for continuous outcomes. Results: A total of 77 PCL lesions were identified. Most were identified on screening or surveillance colonoscopies or colonoscopies performed after abnormal imaging (61.8%). Diffuse large B cell lymphoma (DLBCL) had the highest prevalence (N = 24), followed by follicular lymphoma (n = 21), mantle cell (n = 16), mucosa-associated lymphoid tissue (MALT) (n = 14), then Burkitt’s (n = 2). More mantle cell (93.8%) and follicular (90.5%) lymphomas were sessile. More MALT lymphomas were ulcerated (71.4%). A higher proportion of follicular (76.2%) and mantle cell (71.4%) lymphomas were diminutive (≤5 mm). More MALT (78.6%), DLBCL (75.0%), and Burkitt’s (100%) were large (≥20 mm). More lesions were found in the sigmoid colon (26.0%), followed by the rectum (22.1%), transverse colon (18.2%), cecum (18.2%), descending colon (10.4%), and ascending colon (5.2%). Overall, most underwent immunotherapy (61.3%) and did not have radiation therapy (81.3%), endoscopic resection (75.0%), and surgery (68.8%). Patients with DLBCL demonstrated higher rates of chemotherapy (70.6%), immunotherapy (87.5%), and remission after intervention (52.9%). Conclusions: Primary colorectal lymphomas display distinct macroscopic features and appear in different locations depending on the histopathologic subtype. Most cases are identified at early stages on screening colonoscopies and demonstrate a 75% two-year survival rate. Full article

Purpose: To present the current state of knowledge and our diagnosed patients with congenital stationary night blindness. Material and methods: Data from the PubMed database on CSNB and the presentation of patients with complete and incomplete forms of this condition. Patients underwent routine ophthalmologic examination, optical coherence tomography, and full-field elecroretinogram (ERG-ISCEV), ON-OFF ERG. Results: CSNB is a group of rare, non-progressive retinal diseases characterized by impaired night vision from birth, reduced visual acuity, myopia, nystagmus, and strabismus. Color vision and fundus imaging are most often normal. CSNB is mainly inherited autosomal recessively. Eighteen genes with more than 360 pathogenic variants have been detected in this condition. The effect of gene mutations is to damage the function of rods (Riggs type) and bipolar cells of the retina (Schubert–Bornstein type). The key diagnostic test in CSNB is ERG. In diagnosed cases of complete CSNB the following types have been registered: rod ERG absent, rod–cone response negative (ON bipolar cell defect), and photopic ERG enlarged a-wave. In incomplete CSNB-rod ERG-subnormal, rod-cone response-negative (bipolar cell defect ON, OFF), photopic ERG-subnormal with a double peak in the flicker fusion frequency. Knowledge of the phenotypic changes associated with various gene pathogenic variants is still very limited, hindering the ability to correctly diagnose a patient based on clinical examination and additional ophthalmologic tests. However, some phenotypic features found in our cases were consistent with pathogenic variants previously described in the literature and helped to make a diagnosis that was proven by genetic testing. Conclusions: Congenital stationary night blindness should be considered in the diagnosis of retinal diseases manifesting with impaired night vision. A correct diagnosis is especially important for the patients, as it is nonprogressive, unlike other diseases that should be considered in the differential diagnoses. Full article