Search Results (757)

Systemic sclerosis (SSc) is a disease in which malfunctioning immune cells lead to the formation of autoantibodies that damage blood vessels and body tissues. Fibrosis then develops in the affected organs. Its complex pathogenesis involves multiple immune and stromal cell types, soluble mediators, and dysregulated tissue repair, resulting in heterogeneous clinical manifestations and poor prognosis. Current disease-modifying therapies provide only modest benefits, often slowing but rarely reversing disease progression, and are associated with considerable adverse effects. These limitations have spurred the development of cell-based therapeutic strategies aimed at restoring immune tolerance and promoting tissue repair. In this review, we summarize recent advances in hematopoietic stem cell transplantation, mesenchymal stem cell therapy, and adoptive regulatory T cell transfer and highlight the emerging role of chimeric antigen receptor (CAR)-T cell therapy as a transformative approach for SSc. Collectively, these evolving strategies hold the potential to improve survival, achieve durable remissions, and significantly enhance quality of life for patients with SSc. Full article

Background: Tracheobronchopathia osteochondroplastica (TO) is a rare benign disorder characterized by submucosal cartilaginous and osseous nodules of the tracheobronchial tree, typically sparing the posterior membranous wall. Involvement of the vocal cords is exceedingly rare and may result in critical airway obstruction. The underlying genetic and molecular mechanisms of TO remain largely unexplored. Case presentation: We report a rare case of TO extending from the vocal cords to the bronchi in a 76-year-old man who initially presented with pneumonia and later developed acute respiratory failure due to severe airway narrowing, necessitating emergency tracheostomy. Bronchoscopy and computed tomography revealed diffuse calcified nodules involving the anterior and lateral airway walls, including the subglottic region. Histopathology demonstrated chronic inflammatory cell infiltration with squamous metaplasia. To explore the molecular basis of this condition, whole-genome sequencing (WGS) was performed using peripheral blood samples—the first such application in TO. WGS identified 766 germline mutations (including 27 high-impact variants) and 66 structural variations. Candidate genes were implicated in coagulation and inflammation (KNG1), arachidonic acid metabolism and extracellular matrix remodeling (PLA2G4D), ciliary dysfunction and mineralization (TMEM67), vascular calcification (CDKN2B-AS1), smooth muscle function (MYLK4), abnormal calcification (TRPV2, SPRY2, BAZ1B), fibrotic signaling (AHNAK2), and mucosal barrier integrity (MUC12/MUC19). Notably, despite systemic germline mutations, calcification was restricted to the airway. Conclusions: This case highlights that TO with vocal cord involvement can progress beyond a benign course to cause life-threatening airway obstruction. Integrating clinical, histological, and genomic findings, we propose a novel pathophysiological model in which systemic genetic susceptibility interacts with local immune cell infiltration and fibroblast-driven extracellular matrix remodeling, resulting in airway-restricted dystrophic calcification. This first genomic characterization of TO provides new insights into its pathogenesis and suggests that multi-omics approaches may enable future precision medicine strategies for this rare airway disease. Full article

The aim of the evaluation was to gather information on parents’ experiences and attitudes towards the Irish National Newborn Bloodspot Screening Programme (NNBSP). An interviewer-administered survey was completed by 151 parents whose babies underwent newborn bloodspot screening (NBS) between 2023 and 2025 and for whom the screening result was normal. Results suggest that NBS is highly acceptable to parents, with 100% glad their baby underwent screening. The majority (95%) felt they were provided the information needed to understand the importance of NBS for their baby, and 93% are in favour of screening for more conditions. Positive aspects of NBS reported by parents included the following: blood sampling being undertaken in the home, the sample-taker being very nice and being advised in advance to keep the baby’s heel warm to ease the sampling process. Negative aspects of NBS reported included the following: having to return to the hospital for sampling, the baby becoming distressed, not receiving adequate information and not receiving the screening results. Parents were more likely to report negative experiences if the sample was not taken at home and if the sample was taken by a healthcare professional other than a public health nurse. Parents offered recommendations for improvements to the programme. This study provides important insights into parents’ experiences and attitudes towards NBS in Ireland. Full article

Creutzfeldt–Jakob disease (CJD) is a rare but devastating neurodegenerative disorder characterized by the pathological misfolding of the cellular prion protein (PrP^C) into the pathogenic isoform-scrapie prion protein (PrP^Sc), ultimately leading to fatal outcomes. Cerebrospinal fluid (CSF) biomarkers play a pivotal role in early diagnosis, longitudinal monitoring, and prognostic assessment, thereby enhancing the clinical management of this challenging disease. This review summarizes the established CSF biomarkers, 14-3-3 protein, tau protein (total tau), phosphorylated tau isoforms, α-synuclein, neurofilament light chain (Nfl), S100B, neuron-specific enolase (NSE), and phosphorylated neurofilament heavy chain (pNFH), highlighting typical sensitivity ranges (14-3-3 ~70–85%; RT-QuIC > 90%) and subtype-dependent performance variation. We further dissect limitations related to assay variability, inter-laboratory cut-off inconsistencies, and reduced specificity in non-prion dementias. Looking ahead, we discuss emerging multi-omics discovery, integration of CSF with blood-based biomarkers and imaging signatures, and AI-enabled diagnostic modeling. We propose a three-tier biomarker framework combining Real-Time Quaking-Induced Conversion (RT-QuIC) as a confirmatory assay, tau/NfL/pNFH as injury-severity indicators, and multi-omics-derived signatures for early detection and prognosis stratification. Full article

Subacute sclerosing panencephalitis (SSPE) is a rare, progressive, and fatal neurological disorder caused by persistent measles virus infection. Reliable prognostic biomarkers remain limited. Systemic inflammation has been implicated in the pathogenesis of neuroinfectious diseases, and hematology-derived indices are increasingly recognized as accessible markers of inflammatory burden. This retrospective case–control study was conducted at İnönü University Faculty of Medicine, Malatya, Türkiye, between 2010 and 2025, including 40 pediatric patients with SSPE and 40 age- and sex-matched healthy controls. Demographic and laboratory data were retrieved from institutional records, and disease severity was classified according to Jabbour stages. Compared with controls, patients with SSPE had significantly higher pan-immune inflammation value (PIV: 710.5 [320–1050] vs. 280.0 [150–460], p < 0.001), systemic immune-inflammation index (SII: 640.0 [310–1240] vs. 410.0 [210–720], p = 0.02), and neutrophil-to-lymphocyte ratio (NLR: 2.1 [1.2–3.8] vs. 1.6 [1.0–2.5], p = 0.03), along with lower lymphocyte counts (p = 0.04). Elevated PIVs were strongly associated with advanced Jabbour stages, impaired ambulation, and a higher case-fatality ratio (35%). Multivariate regression identified PIV as an independent predictor of death (OR: 3.25, 95% CI: 1.45–7.28, p = 0.004), and receiver operating characteristic analysis demonstrated superior discriminative accuracy of PIV (AUC = 0.87) compared with other indices. These findings suggest that PIV, a simple and inexpensive biomarker derived from routine blood tests, may provide useful prognostic information in SSPE and aid early risk stratification. Further multicenter, prospective studies are warranted to validate its clinical utility. Full article

Background: Midaortic Syndrome (MAS) is a rare vascular condition characterized by segmental narrowing of the thoracic and abdominal aorta, often involving ostial narrowing of the renal or visceral arteries. While open surgical repair has been the standard treatment, it carries significant morbidity, especially in high-risk patients. Endovascular techniques, including the Chimney approach, provide a minimally invasive alternative to preserve and reestablish both aortic and branch vessel perfusion. This study evaluates the feasibility, safety, and early and midterm outcomes of the Chimney technique used in a cohort of patients with MAS. Methods: Between 2019 and 2025, 9 patients with MAS and branch vessel involvement underwent endovascular repair using the Chimney technique at Brüderklinikum Julia Lanz Hospital in the Mannheim Teaching Hospital of Heidelberg University. Pre-procedural planning was based on computed tomography angiography. Technical success, peri-procedural complications, changes in blood pressure, renal function, and target-vessel stent patency were monitored. Patients were followed over a median of 3 years (range, 0.08–6 years). Results: Nine patients (mean age 77.2 ± 8.7 years; 66.6% female) underwent endovascular repair for midaortic syndrome. All patients were unfit for open surgery. Comorbidities included hypertension (100%), coronary artery disease (100%), and chronic kidney disease (77.7%). Technical success and target-vessel patency were 100%, with no intraoperative deaths, impairment of renal function, or 30-day mortality. One patient (11.1%) developed an access-site hematoma, which was managed conservatively. Median hospital stay was 6 days. During a median 3-year follow-up (range 1 month–6 years), all chimney stents remained patent, patients experienced durable symptom relief, blood pressure improvement, and freedom from reintervention. Conclusions: The Chimney technique offers a safe and effective endovascular option for high-risk patients with Midaortic Syndrome, achieving high technical success, preserved branch-vessel patency, and improvement of symptoms. Larger studies with longer follow-up are warranted to confirm durability and optimize patient selection for this technique. Full article

Background: Postoperative hemorrhage (POH) is a rare yet serious complication of cranial surgery, potentially resulting in extended hospitalization, neurological impairment, or death. Existing predictive models often encompass diverse cranial pathologies, despite differing mechanisms of POH depending on the underlying condition. There is a lack of large-scale investigations focusing exclusively on POH following surgery for intracranial tumors. This study aimed to assess demographic variables—age, sex, and blood type—and pre-existing medical conditions as potential risk factors for POH in this specific context. Methods: A retrospective review was conducted on medical records of 1862 adult patients who underwent primary surgical resection of intracranial tumors. Univariate and multivariate analyses were applied to identify associations between POH and demographic or clinical characteristics. Results: POH, defined as postoperative hematoma necessitating surgical evacuation, was observed in 31 patients (1.7%). Univariate analysis revealed no statistically significant correlation between POH and demographic factors (age, sex) or pre-existing conditions such as hypertension, diabetes mellitus, cardiac disease, or liver dysfunction. Conclusions: The study found no evidence that demographic variables or pre-existing medical conditions independently contribute to the risk of POH following intracranial tumor resection in adults. Full article

Congenital umbilicobiliary fistula is a rare disease reported in humans and dogs. A 2-month-old, intact, male French Bulldog presented with a greenish-yellow discharge dripping from the umbilicus since birth. Complete blood count and serum biochemistry were within normal limits, but serum alkaline phosphatase activity was mildly elevated. A positive contrast cystogram was performed to rule out a patent urachus and confirmed the presence of a vesicourachal diverticula, a type of urachal anomalies. An abdominal ultrasound and computed tomography fistulogram demonstrated a communication between the umbilicus and common bile duct, which suggested an umbilicobiliary fistula. Surgical correction of the umbilicobiliary fistula and vesicourachal diverticula was successfully performed with an uneventful recovery. Histological analysis of the fistulous tract demonstrated a cuboidal/columnar lining epithelium that transitioned to squamous epithelium near the umbilicus. Agenesis of the gallbladder was noted. The application of multiple imaging techniques in the diagnosis and surgical correction of these congenital abnormalities (umbilicobiliary fistula, gallbladder agenesis, and vesicourachal diverticula) was beneficial for treatment planning and outcome. Full article

Hereditary Hemorrhagic Telangiectasia (HHT), also known as Rendu–Osler–Weber syndrome, is a disorder of angiogenesis characterized by mucocutaneous telangiectasias and visceral arteriovenous malformations. This rare autosomal dominant disorder is caused by pathogenic variants in the ENG and ACVRL1 genes, and only 1–3% of case variants occur in SMAD4. HHT clinical manifestations include telangiectasias, epistaxis, and arteriovenous malformations in multiple organ systems. Clinical diagnosis is based on Curaçao Criteria. Here, we describe a pauci-symptomatic 10-year-old girl with an orbital and sinus infectious disease. Her clinical history was unremarkable, except for sporadic, self-limiting epistaxis episodes. She showed finger clubbing and low oxygen saturation levels on pulse oximetry, suggesting a chronic lung disease, and a large lung arteriovenous malformation. She also developed acute neurological symptoms, with evidence of multiple cerebral abscess lesions on MRI. HHT was therefore suspected and confirmed by genetic analysis, which revealed a de novo pathogenic variant in the ENG gene [c.1183G>T p.(Glu395Ter)] found in only 15% of the reads from NGS analysis, performed on peripheral blood lymphocytes, indicating a possible mutational mosaicism. This case outlines that HHT could present with unusual clinical symptoms highlighting the importance of diagnosis using both clinical criteria and genetic test. Full article

Background: Non-arteritic anterior ischemic optic neuropathy (NAION) is a neuroophthalmological disorder characterized by impaired blood flow to the optic nerve head. There is uncertainty about whether, in some cases, NAION may be caused by proximal embolism of the posterior ciliary arteries. Diffusion-weighted magnetic resonance imaging (DWI-MRI) can provide evidence of concurrent cerebral infarction that may indicate a common embolic etiology. Methods: Adults with ophthalmological diagnosis of NAION who underwent cerebral DWI-MRI within 14 days from onset of visual impairment were included in a retrospective cohort study (2013–2021). DWI-MRI images were assessed for presence, location, and type of ischemic stroke by a board-certified neuroradiologist blinded for clinical patient data. Results: Among 122 patients (mean age 64.6 ± 11.9 years), DWI-MRI indicated acute/subacute ischemic stroke in three cases (2.5%), all located within the anterior circulation in the territory of the left middle cerebral artery and ipsilateral to the affected eye in two cases (1.6%). Ischemic stroke location was cortical in one case (0.8%) and subcortical in two cases (1.6%). Acute ischemic stroke indicated by a hyperintense DWI signal and corresponding low ADC was present in one patient (0.8%). Two patients (1.6%) had subacute ischemic stroke (hyperintense DWI signal and normal or elevated ADC signal). Only one NAION patient (0.8%) had acute embolic stroke corresponding to the vascular territory of the affected eye. Conclusions: Concurrent embolic ischemic stroke in NAION is exceedingly rare. Our findings support the prevailing pathophysiological theory of NAION as a non-embolic disease. Full article

Background: Detecting low-frequency mutations is crucial for predicting prognosis and monitoring minimal residual disease (MRD) in acute myeloid leukemia (AML). However, the presence of abundant wild-type sequences hinders the detection of rare mutant alleles. We present a highly sensitive method called ACE (Amplifying–Cleaving–Enriching) to selectively enrich mutant sequences. Methods: ACE includes three steps: (1) initial PCR amplification using biotin-labeled primers, (2) cleavage of wild-type sequences with a specific restriction enzyme, and (3) enrichment of undigested mutant alleles via streptavidin-labeled magnetic beads. Results: Using two rounds of ACE, we achieved over 80,000-fold enrichment of mutant sequences carrying FLT3-TKD, enabling the detection of mutant alleles at levels as low as 0.0001% in AML patient blood samples. Additionally, the ACE method can be adapted to nearly any driver mutation by introducing wild-type-specific restriction sites through PCR with mismatched primers, which has been validated in the IDH1 mutation. Furthermore, the ACE method can be flexibly integrated into conventional detection techniques including Sanger sequencing, quantitative real-time PCR, allele-specific PCR, and even with advanced techniques like droplet digital PCR. Conclusions: ACE significantly enhances the sensitivity of existing techniques for rare mutation detection and holds potential for broad clinical applications. Full article

Danon Disease (DD) is a rare X-linked autophagic vacuolar myopathy caused by pathogenic variants in the lysosome-associated membrane protein 2 (LAMP-2) gene. Alternative splicing of the terminal exon 9 leads to the creation of three different isoforms, each with essential roles in regulating autophagy. DD is characterized by cardiomyopathy, skeletal myopathy, cognitive impairment, and retinal disorders, with cardiac involvement being the primary cause of morbidity and mortality. Muscle biopsy may reveal signs of vacuolar myopathy, but the diagnosis is typically confirmed through sequencing and deletion/duplication analysis of the LAMP-2 gene using peripheral blood. Although few genotype–phenotype correlations have been described, with most being limited to isoform 2B of exon 9, the most significant prognostic indicator remains sex. The disease manifests earlier and with a more severe systemic presentation in males due to their hemizygous status, whereas in females, the typical presentation is late-onset hypertrophic or dilated cardiomyopathy, generally without extracardiac involvement. Cases of severely affected women have been described, potentially due to non-random or defective X-inactivation. The less typical and delayed clinical presentation in females can result in incorrect or missed diagnoses. The aim of this narrative review is to summarize the natural history, diagnostic criteria, management strategies, and recent advancements in the understanding of DD in women. Full article

Background: Evans syndrome is a rare autoimmune disease characterized by immune thrombocytopenia (ITP), autoimmune hemolytic anemia (AIHA), and autoimmune neutropenia, typically triggered by an episode of immune dysregulation or multiple other factors. We present what appears to be the first reported case of Evans syndrome developing in a 66-year-old female following respiratory syncytial virus (RSV) vaccination. Case Presentation: A 66-year-old female presented with a petechial rash on her arms, legs, and face. Laboratory tests revealed a platelet count of 1 × 10⁹/L, significantly lower than her historical baseline of >200 × 10⁹/L. On hospital day 4, her hemoglobin declined from 14.3 g/dL to 9.9 g/dL, with laboratory evidence of hemolysis, including elevated bilirubin, low haptoglobin, and increased lactate dehydrogenase (LDH). Bone marrow biopsy revealed megakaryocytic hyperplasia consistent with ITP, along with a small polyclonal B-cell population lacking CD20 expression. Imaging was unremarkable, showing no interval changes aside from stable pre-existing pulmonary nodules and no lymphadenopathy. These findings supported a diagnosis of Evans syndrome. Initial therapy with dexamethasone and intravenous immunoglobulin (IVIG) for presumed ITP was ineffective. Due to refractory thrombocytopenia, the patient initially received one dose of rituximab, followed by one dose of romiplostim. Subsequently, the patient received rituximab infusions every week at a rate of 375 mg/m² for four doses, as well as prednisone at a dose of 1 mg/kg/day. Within five weeks, her blood count returned to normal. Conclusions: This case raises concern for a potential temporal association between RSV vaccination and the onset of Evans syndrome. It underscores the need for heightened clinical awareness and further investigation into immune-mediated hematologic complications following RSV immunization. Full article

We carried out a comprehensive literature search for publications on the range of vascular events that have been linked to adenomyosis. This covered vascular diseases, blood coagulation disorders, thrombosis, hypercoagulation, stroke (embolic, ischemic, thrombotic, hemorrhagic), cerebrovascular episodes, cerebral infarction, cerebral hemorrhage) and renal disease. This review covers 63 articles. Nineteen articles reported clinical manifestations of intravascular thrombosis in women with adenomyosis. Eleven publications were identified that reported on cerebral involvement and adenomyosis, including cases of ischemic stroke or infarction. Dysregulation primarily seems to occur via local factors leading to altered angiogenesis. Five case reports were identified that reported on various vascular complications attributed to the presence of adenomyosis. The search also identified reports of cerebral complications in women with adenomyosis. Through a secondary search, we identified publications dealing with a possible connection between cardiac complications and renal pathology, which the authors attributed to adenomyosis. Vascular involvement in adenomyosis is documented in rare cases by the presence of endometrial tissue in myometrial vessels both in menstrual and non-menstrual uteri. Women with adenomyosis have a higher platelet count, a shorter thrombin and prothrombin time and an activated partial thromboplastin time. These findings has been applied to attempts to identify therapies for adenomyosis based on targeting the vasculature, but the existence of a link between the two conditions is under question for several reasons: only case reports (or very small series) have been published; all published cases come from one region of the world (the Far East); the published literature does not contain objective proof of a causal relationship between the two pathologies, except for the elevation of some markers. In summary, it is not possible to conclude that the presence of adenomyosis has a pathogenetic role in causing vascular events, first and foremost because available evidence consists mostly of case reports. Full article

Introduction: Cardiac sarcoidosis (CS) is a rare but potentially life-threatening manifestation of systemic sarcoidosis, often leading to arrhythmias, conduction abnormalities, or heart failure. Diagnosis is challenging due to nonspecific symptoms and the need for advanced imaging or biopsy. Case Presentation: We describe a 49-year-old man admitted with severe decompensated heart failure (NYHA IV). He had a history of complete heart block treated with pacemaker implantation and subsequent CRT-D upgrade. On admission, echocardiography revealed biventricular dysfunction with severe mitral and tricuspid regurgitation. Cardiac MRI demonstrated extensive non-ischemic late gadolinium enhancement. Blood cultures grew methicillin-sensitive Staphylococcus aureus (MSSA) and intravenous antibiotics were initiated. Despite diuretics and inotropes, his condition deteriorated. Corticosteroid therapy was started due to high suspicion of sarcoidosis. Endomyocardial biopsy confirmed CS. The patient developed neuropsychiatric complications and, despite urgent listing for heart transplantation, died during hospitalization. Conclusions: This case highlights the diagnostic and therapeutic challenges of CS, the limitations of corticosteroid therapy in advanced disease, and the importance of early recognition with advanced imaging modalities. Full article