Search Results (11,575)

Erdheim–Chester Disease (ECD) constitutes a rare and clinically heterogeneous non-Langerhans cell histiocytosis, characterized by the systemic infiltration of tissues by foamy, lipid-laden histiocytes. These cells typically exhibit an immunophenotypic profile positive for CD68 and negative for CD1a. The disease’s multifaceted presentation, which can span from isolated bone lesions to fulminant multi-organ failure, frequently results in considerable diagnostic delay. In this case-based review, we describe the case of a 58-year-old who presented with a primary complaint of exertional dyspnoea and fatigue. The initial diagnostic evaluation revealed a hemodynamically significant circumferential pericardial effusion and imaging findings suggestive of aortitis. Clinical presentation of ECD depends on the organs and tissues involved, and may range from bone pain to neurological symptoms, endocrine dysfunction, and cardiac involvement. Cardiovascular involvement occurs in at least 40% of ECD patients, although it is frequently underdiagnosed. Cardiac ECD is heterogeneous and may mimic many alternative aetiologies. The infiltration of the right atrioventricular sulcus, right atrial walls, or interatrial septum is one of the most typical cardiac manifestations of ECD. Recognition of pseudo-tumour intra-atrial mass, pericardial involvement, as well as the circumferential encasement of the entire aorta, the so-called coated aorta, are other frequent findings. Diagnosis often requires a multimodal approach, in particular when cardiac symptoms represent the onset of clinical manifestation of ECD. The combined use of computed tomography, fluorodeoxyglucose positron emission tomography, dedicated cardiac and abdominal magnetic resonance imaging, and X-ray of long bones can collectively reveal a constellation of findings diagnostic of ECD. Full article

Fibroblast growth factor receptor 2 (FGFR2) inhibitors such as pemigatinib are targeted therapies for cholangiocarcinoma with FGFR2 alterations. While generally well tolerated, they are associated with unique adverse events. Calciphylaxis, a potentially fatal vascular calcification disorder, is a rare complication. We present a 43-year-old woman with metastatic intrahepatic cholangiocarcinoma harboring an FGFR2 fusion who developed calciphylaxis after seven months of pemigatinib therapy. Despite drug discontinuation, antibiotics, and multidisciplinary supportive care, she deteriorated rapidly and died from sepsis and advanced disease. Histopathological analysis confirmed dermal and vascular calcifications consistent with calciphylaxis. This case highlights the importance of early recognition of cutaneous lesions in patients on FGFR inhibitors. Prompt cessation of therapy, management of metabolic derangements, and consideration of sodium thiosulfate may be lifesaving. Full article

Background/Objectives: Mucinous adenocarcinoma (MAC) is a rare and clinically problematic subtype of rectal cancer, tending to present at an advanced stage and to respond poorly to neoadjuvant therapy. The consistently worse prognosis than that of not-otherwise-specified adenocarcinoma (NOS-AC) is not fully understood, potentially owing to intrinsically more aggressive biology or specific immune evasion mechanisms. We used the IMMUNOREACT multicentre cohort, with external validation in TCGA, to investigate the clinical and immunological features of rectal MAC in detail. Methods: Two hundred patients with rectal adenocarcinoma (16 MAC, 184 NOS-AC) from the IMMUNOREACT 1 (NCT04915326) and IMMUNOREACT 2 (NCT04917263) prospective cohorts were included. To account for the imbalance in baseline characteristics, propensity score matching (PSM) was performed on age, sex, neoadjuvant treatment and TNM stage. The immune microenvironment was characterised using immunohistochemistry (CD3, CD4, CD8, CD8β, Tbet, FoxP3, PD-L1, MSH6, PMS2, CD80), flow cytometry and NanoString PanCancer IO 360™ transcriptomics of adjacent healthy mucosa. Findings were externally validated against TCGA rectal and colon adenocarcinoma datasets. Results: MAC presented at significantly more advanced stage than NOS-AC across all TNM parameters: higher T stage (p = 0.006), N stage (p < 0.001), M stage (p = 0.039) and overall TNM stage (p < 0.001). In the unmatched cohort, MAC was associated with worse overall survival (HR 2.53; 95% CI 1.03–6.23; p = 0.043) and disease-free survival (HR 2.86; 95% CI 1.25–6.55; p = 0.013), but both differences became non-significant after PSM. MAC patients had higher haemoglobin after adjusting for confounders (mean difference [MD] 1.26 g/dL, 95% CI 0.30–2.31, p = 0.012), consistent with a hypothesis of reduced chronic rectal bleeding as a possible mechanism for late presentation. Transcriptomically, MAC showed suppression of HLA class II antigen presentation genes (HLA-DQA1, HLA-DQB1, HLA-DRB1) and myeloid activation genes (S100A8/A9/A12) in adjacent healthy mucosa. Loss of MMR proteins MSH6 and PMS2 in histologically normal mucosa was significantly more frequent in MAC. These findings were replicated in the TCGA cohort, which also showed lower tumour mutational burden and a distinct mucin-associated transcriptomic profile in MAC. Conclusions: The worse outcomes of rectal MAC appear to be driven largely by late-stage presentation, possibly owing to later diagnosis. MAC nonetheless carries a distinct immune phenotype, detectable even in histologically normal surrounding mucosa, that likely contributes to its treatment resistance. These observations provide a basis for developing histotype-specific approaches to both early detection and treatment in this uncommon but clinically challenging tumour subtype. Full article

Background: Hydatid disease, caused primarily by Echinococcus granulosus, remains a significant public health challenge in endemic regions. While hepatic (80–85%) and pulmonary (15–20%) involvements are common, multi-organ dissemination involving rare sites such as the pericardium, diaphragm, and mediastinum occurs in less than 0.1–2% of cases. Case presentation: We present a rare case of a 26-year-old male, a farmer for 10 years, with occupational exposure to dogs and horses, with a personal history of multiple surgically treated abdominal cysts in 2016, admitted after abdominal computed tomography revealed liver cysts greater than 5 cm, as well as mediastinal and diaphragmatic cysts. Histopathological examination of the surgically resected hepatic cyst material confirmed echinococcosis. Serology was also positive for echinococcosis. Echocardiography revealed a pericardial cyst, posterior to the left atrium. Under these circumstances, antiparasitic treatment was initiated by an infectious disease specialist, followed by surgical treatment of the abdominal cysts, confirming the final diagnosis of hydatid disease, and subsequently, surgical treatment of the thoracic hydatid cysts was performed. The postoperative course was complicated by bronchial superinfection with Stenotrophomonas maltophilia, identified from bronchial aspirate culture after extended incubation and managed with trimethoprim–sulfamethoxazole. Conclusions: This case underscores the necessity of lifelong surveillance in hydatid disease, the potential role of postoperative antiparasitic therapy in preventing long-term recurrence, and the vital role of a multidisciplinary team in managing complex, disseminated relapses. Full article

Introduction: The Melody transcatheter pulmonary valve (TPV) was the first percutaneous bioprosthetic valve approved for transcatheter pulmonary valve implantation (TPVI). We report our single-centre experience with Melody TPV implantation in patients with congenital heart disease (CHD). Methods: This retrospective observational single-centre study included all patients evaluated in the catheterization laboratory for Melody TPV implantation. Early outcomes included procedural failure, life-threatening adverse events, and mortality. Long-term outcomes assessed during follow-up included infective endocarditis, transcatheter reintervention, and surgical reintervention. Results: Between 2015 and 2025, 50 consecutive patients were evaluated for TPVI with the Melody TPV at our institution. In four patients (8%), the procedure was aborted because of coronary artery compression detected during balloon interrogation of the right ventricular outflow tract (RVOT). One patient (2%) died of septic shock following acute pulmonary oedema in the immediate post-procedural period. The remaining 45 patients (90%) underwent successful Melody TPV implantation and were discharged from hospital. In six patients, the Melody TPV was implanted off-label: in the tricuspid position (n = 2) and in small conduits (<16 mm) (n = 4). Mean follow-up duration was 5.8 ± 3.6 years. One patient was lost to follow-up. Among the remaining 44 patients, seven (15.9%; 2.7% per patient-year) developed infective endocarditis, seven (15.9%; 2.7% per patient-year) underwent transcatheter reintervention (six balloon dilatations of the Melody valve and one valve-in-valve implantation), and four (9.1%; 1.5% per patient-year) required surgical replacement of the Melody TPV. Conclusions: Transcatheter implantation of the Melody TPV is an effective treatment for RVOT dysfunction. At mid-term follow-up, the majority of implanted Melody valves demonstrated satisfactory function, and only a minority of patients required surgical valve replacement. Full article

Introduction: Pregnancy in women with end-stage kidney disease (ESKD) remains rare and high-risk, despite advancements in dialysis and supportive care. Using a nationwide database in South Korea, this study examined the maternal and neonatal outcomes among women undergoing maintenance hemodialysis, with a particular focus on dialysis modality and treatment patterns. Methods: This population-based retrospective cohort study utilized data from the Korean National Health Insurance Service database. The study included all live births between 1 January 2014 and 31 December 2022, linked to mothers who underwent hemodialysis at least twice per week during pregnancy. Results: Between 2014 and 2022, in the Republic of Korea, 31 live births were recorded among 29 women undergoing hemodialysis. The mean maternal age at delivery was 36.1 ± 4.94 years, and most patients had significant comorbidities, including hypertension (79.3%), and diabetes mellitus (48.3%). Cesarean section was the predominant mode of delivery (75.9%). Pregnancy-related complications included preterm delivery (48.4%), preeclampsia (16.1%), and gestational diabetes (16.1%). A total of 16.1% of the neonates had atrial septal defects. During the peripartum period, 93.1% of deliveries occurred at tertiary care centers, and trimester-wise escalation in dialysis frequency was observed. Conclusions: This study provided real-world data on pregnancy-related outcomes among women with ESKD undergoing maintenance dialysis in Korea. Given the rarity of this clinical condition, our findings may serve as a valuable reference for the management of pregnant women with ESKD. Full article

Background: Thyroid cancer is increasing, particularly the differentiated type, with decreasing incidence of the anaplastic type. Anaplastic thyroid carcinoma (ATC) is a rare, aggressive, and often lethal form. It frequently presents with metastatic disease, regional and systemic, with common distant metastasis to the lung, bone, brain, and adrenal, and rarely to other places. Case presentation: A 74-year-old Arab male presented with symptomatic anemia and melena and was admitted for investigation of the cause. The patient was found to have a large retrosternal goiter and gastric tumor. CT scan showed a pedunculated, nonobstructive mass, suggestive of a GIST or leiomyoma. The neck mass presented with compressive symptoms. He underwent a combined neck and abdominal surgical resection based on a multidisciplinary team decision, as prior biopsies were not conclusive. The final pathology report identified similar tumors in the two specimens and suggested an anaplastic thyroid carcinoma as the primary tumor with metastasis to the stomach. Furthermore, the workup, including a PET scan 2 weeks post-surgery, revealed widespread metastases in the bone, lung, and liver, and the treatment was palliative. He was followed up in the outpatient clinic for 4 and a half months post-operatively. The patient developed sepsis and cardiopulmonary arrest and died. Conclusions: ATC can metastasize to many places in the body, including the stomach (as shown in our case), which can cause significant upper gastrointestinal bleeding and anemia. Metastatic ATC carries a poor prognosis; thus, physicians need to keep a high index of suspicion in approaching similar cases. A multidisciplinary approach for the management is of utmost importance for appropriate treatment. This disease’s pathology, behavior, and targeted new treatment modalities must be explored further. Full article

Analysis of freely moving Drosophila captures complex movement behaviors. However, previous experiments have been limited by the inability to distinguish between falls and downward jumps (downjumps). Here, individual flies moving freely in a culture vial were recorded using a single 58 fps video camera. Upward jumps were readily identified by positive movement in the vertical direction. Several statistical and machine learning methods were used to distinguish between falls and downjumps, including Principal Component Analysis (PCA), K-Means Clustering, Uniform Manifold Approximation and Projection (UMAP), Hierarchical Density-Based Spatial Clustering with Applications to Noise (HDBSCAN) and Shapley Additive Explanations (SHAP). Falls were abundant and characterized by an initial velocity consistent with simple acceleration due to gravity. Downjumps were more rare, and were characterized by a greater initial velocity, indicating active propulsion by the fly. Aged flies took longer to resume movement after a fall, suggesting possible negative effects of falls. Falls in young w[1118]-strain flies exhibited mid-event velocities that were lower than expected, indicating some compensatory behavior that was reduced in aged flies. These methods should facilitate future studies of the effects of aging and neurodegenerative disease models on locomotor behaviors and falls, including the testing of potential interventions. Full article

Cardiac rehabilitation (CR) is strongly recommended in secondary cardiovascular prevention; indeed, in patients after cardiac surgery or with coronary artery disease or heart failure, this intervention is recommended to decrease mortality, morbidity, and disability, and to improve quality of life and cardiorespiratory fitness. Moreover, each step of the cardiovascular continuum denotes a potential risk factor for the progression of cognitive frailty; this interaction is highly prevalent, affecting approximately one-third of all patients in cardiology settings. For these reasons, CR should consider the patient’s cognitive domain; however, cognitive assessment is still rarely integrated into standard CR protocols. Therefore, this comprehensive review presents current evidence and recent updates on the interaction between CR and cognitive impairment, focusing on physiological mechanisms, core components, benefits, and strategies for implementing CR in patients with cognitive frailty to optimize recovery and prognosis. Full article

Background: Rare diseases are associated with chronic progression, functional impairment, and complex care needs, requiring long-term and coordinated rehabilitation. Physical and Rehabilitation Medicine (PRM) plays a key role in maintaining functional capacity and improving quality of life; however, access to rehabilitation services remains uneven across regions. Aim: This study aims to assess the regional structural availability of PRM services across Bulgaria and to identify territorial differences in the organizational profile of rehabilitation services that may influence the potential availability of rehabilitation care for patients with rare diseases. Methods: A descriptive cross-sectional study was conducted using publicly available aggregated data from the NHIF and the National Statistical Institute as of 31 December 2024. Structural indicators included the number of outpatient and inpatient PRM healthcare facilities and PRM specialists, standardized per 100,000 population, as well as the outpatient-to-inpatient facility ratio (OFs/IFs). Hierarchical cluster analysis (Ward’s method, Euclidean distance) was applied as an exploratory tool to identify similarities in regional service availability profiles. Results: Substantial regional differences in the structural availability of PRM services were identified. Outpatient facilities ranged from 4.46 to 6.74 per 100,000 population, while inpatient facilities ranged from 2.30 to 3.42 per 100,000 population. The OFs/IFs ratio varied between 1.30 and 2.26, indicating different organizational profiles of PRM service provision. Exploratory hierarchical clustering suggested two broad regional service profiles: one characterized by a relatively balanced distribution of outpatient and inpatient structures and another characterized by a predominance of outpatient-oriented rehabilitation services. Conclusion: The findings reveal substantial regional differences in the organization of PRM services in Bulgaria. Regions with a predominance of outpatient structures may demonstrate different capacities for delivering comprehensive rehabilitation services, particularly for patients with complex long-term needs, including rare diseases. The results highlight the need for targeted regional planning, improved integration of rehabilitation services, and policy measures aimed at ensuring equitable access to care. Full article

Background: Hypertrophic olivary degeneration (HOD) is a rare neurological condition resulting from trans-synaptic degeneration of the inferior olivary nucleus (ION) following disruption of the dentato-rubro-olivary pathway, also known as the Guillain–Mollaret triangle (GMT). Although the clinical and radiologic features of HOD have been previously described, the precise temporal correlation between clinical symptom onset and manifestations on magnetic resonance imaging (MRI) remains difficult to establish, and the factors contributing to accelerated disease progression are poorly understood. Case Presentation: A 43-year-old male presented with intracerebral hemorrhage involving the left midbrain, bilateral pons, and cerebellum. Serial MRI was prospectively performed starting four weeks post-hemorrhage, at which time no signal abnormalities were detected in the ION. However, at 9 weeks, T2 hyperintensity first emerged in the bilateral ION. Approximately 2 weeks after this finding, the patient developed characteristic palatal and lingual tremors, accompanied by a dissociated vertical pendular nystagmus that was predominantly monocular (right eye). In addition, severe dysphagia was also noted, with videofluoroscopic swallowing study (VFSS) showing aspiration across all diets. A subsequent MRI obtained at 13 weeks post-insult (two weeks after tremor onset) revealed newly developed bilateral ION hypertrophy, with the maximal diameter increasing from a 5 mm baseline to 7 mm. Follow-up MRI at 17 weeks post-hemorrhage revealed further progression with increased hypertrophy and signal intensity. Dysphagia persisted throughout the clinical course, ultimately necessitating percutaneous endoscopic gastrostomy (PEG) tube insertion. Conclusions:This case provides rare, longitudinal documentation of the clinico-radiologic progression of HOD, facilitated by a pre-insult baseline MRI and prospective serial imaging. Our findings provide a detailed timeline of the transition from signal abnormality to hypertrophy in correlation with clinical symptom emergence. Full article

Background/Objectives: Krebs von den Lungen-6 (KL-6) is a mucin-like glycoprotein that is elevated in a variety of lung diseases and used as a diagnostic and prognostic biomarker in people with cystic fibrosis (pwCF). Single nucleotide polymorphisms (SNPs) in mucin-1 (MUC1) influence KL-6 serum concentration. This study investigated the relationship between serum KL-6 concentrations in pwCF and a MUC1 SNP and its longitudinal dynamics. Methods: The study included pwCF (n = 174) and healthy controls (n = 30). In pwCF, 365 samples were collected for longitudinal analyses; KL-6 levels were measured and the MUC1 SNP rs4072037 was genotyped in pwCF and controls. Cross-sectional and longitudinal associations between KL-6, genotype, and clinical parameters, such as infectious exacerbation, body mass index, inflammatory values and lung function, were analyzed using linear mixed-effects models. Results: Serum KL-6 was significantly elevated in pwCF compared with controls (458 ± 357 vs. 283 ± 103 U/mL; p < 0.001). Homozygous G/G carriers exhibited higher baseline KL-6 than A/A carriers (627 ± 673 vs. 397 ± 148 U/mL; p < 0.001), while heterozygous individuals showed intermediate levels. Longitudinally, the MUC1 SNP and interindividual differences in vital capacity (ppFVC) primarily determined baseline KL-6 levels, explaining 52.5% of variance. Short-term intraindividual fluctuations were largely driven by infectious exacerbations independent of genotype, accounting for ~10% of within-subject variance. Conclusions: PwCF generally showed elevated serum KL-6 levels and reflected both stable interindividual differences, mainly driven by the MUC1 SNP and ppFVC. Dynamic intraindividualchanges were associated with infectious exacerbations. Given the influence of MUC1 polymorphisms (e.g., rs4072037) on KL-6 concentration, personalized interpretation based on the genotype status may be informative in pwCF. Full article

Ataxia–Telangiectasia (A-T) is a rare neurodegenerative multisystem disease caused by mutations in the A-T Mutated (ATM) gene resulting in cerebellar ataxia, immunodeficiency and an increased cancer risk. Copper and zinc play important roles in similar cellular processes as the ATM protein, such as cell growth, apoptosis, and oxidative stress. This study aimed to explore copper and zinc levels in individuals with A-T since imbalances in these trace elements may contribute to the clinical features commonly seen in A-T and therefore be a target for novel therapies; furthermore we aimed to assess the potential role of copper and zinc as disease biomarkers. In this retrospective cohort study, plasma copper and zinc levels were collected from 37 individuals with A-T and compared with age-related reference values. The results showed lower zinc levels in pediatric individuals with classic A-T, but no differences in copper levels. In adults, copper levels were lower in classic A-T, but not in variant A-T. These findings suggest that copper and zinc metabolisms are dysregulated in A-T, but since mixed model analysis showed minimal changes over time, copper and zinc do not appear to be reliable biomarkers for disease progression. Full article

Understanding the spatial proteomic landscape of human tumors is essential for dissecting cellular heterogeneity and microenvironmental interactions in cancer biology. Traditional bulk proteomic approaches, however, obscure spatial information and average out signals from distinct cell populations. Here, we present a detailed and reproducible micro-quantitative protocol for spatially resolved proteomic analysis of specific cellular subpopulations isolated from immunohistochemistry (IHC)-labeled formalin-fixed paraffin-embedded (FFPE) tissue sections using laser microdissection (LMD). By combining IHC staining to visually define phenotypically distinct cells within preserved tissue architecture and precise LMD capture, approximately 6000 target cells can be isolated per sample for downstream proteomic quantification. Despite the ultra-low input, optimized lysis and digestion steps ensure consistent peptide recovery and highly reproducible label-free LC–MS/MS data across replicates. Integrating immunohistochemistry staining-guided spatial sampling with ultrasensitive quantitative proteomics, this workflow enables reliable cell-type-specific profiling directly within human tumor tissues. The protocol bridges histopathology and proteomics, offering a practical framework for translational research exploring spatial protein signatures and tumor microenvironmental heterogeneity. Full article

Background—Generalized pustular psoriasis (GPP) is a rare and severe inflammatory skin disorder—and evidence regarding relative impact of treatments thereof is currently scant. Objective—We aimed to systematically review and narratively synthesize comparative interventional therapies for GPP and secondarily explore their relative effectiveness through exploratory network meta-analyses (NMAs). Methods—Comprehensive searches were performed in PubMed and EMBASE to identify comparative interventional studies that investigated the impact of biologics in GPP. Bayesian NMAs were conducted only for exploratory analyses. Results—Eleven studies met our inclusion criteria and data from 4 of the 11 were used for NMAs. Methodological heterogeneity was evident; the various biologics demonstrated effectiveness in treating GPP. Inhibitors of interleukin (IL)-36 (e.g., spesolimab) resulted in rapid pustular clearance within one week and sustained reductions in flare occurrence. Inhibitors targeting IL-17, IL-23, TNF, and IL-12/23 also demonstrated high response rates, durable disease control, and improvements in quality of life among diverse patient populations. Results from our exploratory NMAs revealed patterns of relative effectiveness with IL-17 and IL-36 inhibitors that are consistent with the existing literature. However, methodological limitations across the four studies deterred us from making conclusive inferences. Conclusions—Biologic therapies provide significant clinical benefit in patients with GPP. Our narrative syntheses highlight the need for future quantitative syntheses. Full article