Search Results (10,427)

Background/Objectives: Dyslipidemia is increasingly linked to retinal microvascular changes, yet its impact in pediatric populations remains unclear. Given the retina’s role as a microvascular model, this review evaluates the association between dyslipidemia and retinal vascular alterations in children and adolescents. Methods: We conducted a systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines to evaluate the association between lipid profiles, body composition, and retinal vascular parameters in individuals younger than 19 years. Four eligible studies were found. Results: Triglyceride (TG) levels, total cholesterol (TC) levels, low-density lipoprotein cholesterol (LDL-C), and apolipoprotein B (apoB) levels were associated with smaller retinal arteriole diameters (CRAE), whereas there was no consistent association between venular diameter (CRVE) and lipid levels. In addition, families with familial hypercholesterolemia (FH) had lower capillary densities and larger foveal avascular zone areas detected by optical coherence tomography angiography (OCT-A) compared to control subjects. The presence of both obesity and dyslipidemia resulted in greater degrees of arteriolar narrowing. Conclusions: These findings suggest that adverse metabolic profiles in childhood may be linked to early microvascular alterations. However, the limited number of heterogeneous studies highlights the need for larger longitudinal investigations. Full article

Background: Chronic myeloid leukemia (CML) is a rare disease in children and adolescents. Discrepancies have been reported regarding the outcomes of adolescents, most of whom have been studied with younger or older patients not separately. Methods: The International Registry of Pediatric CML (I-CML-Ped Study) retrospectively and prospectively enrolled 614 patients less than 18 years old. Data from adolescents (15–18 years) with CML in chronic phase (CML-CP) were analyzed and compared to data from children less than 15 years old enrolled during the same period. Results: In total, 132 out of 144 adolescents presented with CML-CP: palpable spleen was reported in 67%, and the median leukocyte count was 181 G/L [interquartile range, 70–327]. Responses to treatment and outcome were analyzed in 124 adolescents with imatinib as first-line treatment: the cumulative incidence of major molecular responses (MMR) at months 12 and 36 was 33.4% (95% confidence interval CI, 24.9–41.9) and 79.8% (95% CI, 71.8–87.7), respectively. With a median follow-up of 4 years (95% CI: 3.5–4.9), 49 (40%) of these 124 patients were switched to another treatment, 11 (9%) patients progressed to the advanced phase, and the five-year overall survival rate was 95.2% (95% CI, 90.8–99.9%). We did not find significant statistical differences between these adolescents and younger children receiving imatinib in terms of response (complete cytogenetic response, MMR) and outcome (progression-free survival, overall survival). Conclusions: Response to treatment and outcomes in adolescents with CML-CP in the tyrosine kinase inhibitor era are satisfying without statistically significant difference from results observed in younger children. Full article

The coexistence of systemic sclerosis and sarcoidosis is very rare. Both are systemic autoimmune diseases with lung involvement but different pathogenesis. In contrast to findings of mid- to upper-lobe interstitial lung disease (ILD) that may occur with hilar lymphadenopathy in sarcoidosis, the most common lung manifestation of systemic sclerosis is lower-lobe ILD, which is typically characterized by a non-specific interstitial pneumonia pattern. This distinction in lung involvement between the two diseases is crucial due to the need for different therapeutic approaches. We present a series of three overlap cases: two with sarcoidosis onset before the diagnosis of systemic sclerosis and another with systemic sclerosis onset before the diagnosis of sarcoidosis. Three cases of concomitant sarcoidosis and systemic sclerosis are reviewed, including the pathophysiology of each disease and the shared pathways leading to the development of both conditions. Systemic sclerosis–sarcoidosis overlap is a high-risk phenotype. Early recognition and a personalized, aggressive therapeutic approach are essential to alter the natural course of these two converging fibrotic and granulomatous processes. Full article

Background and Clinical Significance: Vestibular drop attacks are a rare but disabling manifestation of Ménière’s disease. This study aimed to demonstrate the value of multimodal audiovestibular assessment in documenting vestibular deficit after intratympanic gentamicin therapy. Case presentation: A 57-year-old woman with refractory Tumarkin crises underwent serial audiological and vestibular testing before and after intratympanic gentamicin treatment. Post-treatment testing demonstrated right-sided vestibular hypofunction with caloric areflexia, reduced vestibulo-ocular reflex gain, corrective saccades on video head impulse testing, and absent cervical vestibular-evoked myogenic potentials. Hearing thresholds showed transient deterioration with near-baseline recovery during follow-up. Vestibular drop attacks resolved completely. Conclusions: Multimodal audiovestibular assessment provides objective documentation of treatment-induced vestibular hypofunction after intratympanic gentamicin therapy in refractory Ménière’s disease. Full article

Background: Pycnodysostosis is a rare autosomal recessive skeletal disorder caused by biallelic pathogenic variants in CTSK, which encodes cathepsin K, a lysosomal cysteine protease required for osteoclast-mediated degradation of bone matrix. Case Report: We describe a girl with short stature, skeletal deformities, osteosclerosis, craniofacial features, clavicular dysplasia, and radiological evidence of fractures. Clinical exome sequencing identified two heterozygous CTSK variants, c.85T > C (p.Trp29Arg) and c.679A>T (p.Ile227Phe), both currently classified as variants of uncertain significance. Segregation analysis showed that the variants were inherited in trans. Computational modeling and in silico prediction tools supported a possible deleterious effect on cathepsin K structure or function. Serum cathepsin K was higher in the patient than in two age-matched controls; this result is reported as an exploratory observation only. Increased serum cathepsin K may reflect altered expression, secretion, clearance, or accumulation of dysfunctional protein, but cannot be interpreted as proof of compensatory upregulation. Conclusions: The patient’s clinical and radiographic features, the biallelic trans configuration of the CTSK variants, their rarity in population databases, and computational predictions support p.Trp29Arg and p.Ile227Phe as strong candidate disease-associated variants. Functional studies are required to confirm their effect on cathepsin K expression, maturation, and enzymatic activity. Full article

Background and Clinical Significance: Tumefactive Multiple Sclerosis (TMS) represents a rare and diagnostically challenging form of demyelinating disease characterized by large space-occupying lesions that can closely mimic intracranial neoplasms, abscesses, and other inflammatory or vascular conditions. Case Presentation: The case highlights the overlapping radiologic features that frequently lead to diagnostic uncertainty and underscores the importance of careful interpretation of multimodal imaging and ancillary studies. Overall a comprehensive multidisciplinary evaluation is essential to reduce the risk of misdiagnosis and avoid unnecessary invasive interventions. Conclusions: This review summarizes current evidence regarding the diagnostic approach, imaging characteristics, and therapeutic strategies for tumefactive demyelinating lesions. Additionally, we present a clinical case that illustrates the diagnostic complexity of this entity, in which neuroimaging findings and cerebrospinal fluid analysis supported a demyelinating rather than neoplastic process. Full article

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

Cancer therapies have significantly improved survival but are frequently limited by cancer therapy-related cardiovascular toxicity (CTR-CVT). Cardiovascular imaging plays a central role in baseline risk stratification, surveillance during therapy and long-term follow-up. Transthoracic echocardiography (TTE) remains the first-line imaging modality; however, conventional parameters such as left ventricular ejection fraction (LVEF) often fail to detect early myocardial injury. Myocardial deformation imaging, particularly global longitudinal strain (GLS), has emerged as a sensitive marker of subclinical dysfunction across multiple cardiotoxic phenotypes. Cardiac magnetic resonance (CMR) further enhances diagnostic accuracy through tissue characterization techniques, enabling the detection of myocardial edema, inflammation, and fibrosis before overt functional decline. Different anticancer therapies induce distinct pathophysiological mechanisms of injury, each associated with characteristic imaging patterns. Emerging imaging biomarkers and multimodality approaches may improve early detection, the spatial characterization of myocardial injury and individualized surveillance strategies. Pediatric patients represent a uniquely vulnerable population due to their myocardial immaturity, altered pharmacokinetics and prolonged post-treatment life expectancy, resulting in a higher cumulative lifetime cardiovascular risk. In conclusion, a mechanism-based multimodality imaging approach integrating echocardiography, CMR and emerging data-driven technologies is essential to optimize early detection, risk stratification and long-term cardiovascular outcomes in both adult and pediatric cardio-oncology populations. Full article

Background/Objectives: Tezepelumab targets thymic stromal lymphopoietin and has broad efficacy in severe asthma, yet real-world evidence on patient-reported trigger burden remains limited. We assessed 12-month outcomes after tezepelumab, focusing on clinical remission, biomarkers, and trigger profiling as complementary dimensions of response. Methods: In this multicenter longitudinal real-world observational cohort based on routine clinical follow-up and Severe Asthma Network in Italy (SANI) registry data, 43 adults with severe asthma treated with tezepelumab at four Italian SANI reference centers were evaluated at baseline and, when available, after 1, 3, 6, and 12 months. Outcomes included exacerbations, lung function, type 2 biomarkers, the Asthma Control Test, SNOT-22, trigger categories, Asthma Trigger Inventory (ATI) scores, and SANI-defined clinical remission. Results: Among 22 patients with 12-month follow-up data, mean annualized exacerbations decreased from 4.30 ± 2.77 to 0.36 ± 0.49 (p < 0.001), and 14/22 (63.6%) were exacerbation-free. Asthma control improved, whereas FEV1 remained stable. FeNO and blood eosinophils decreased at selected time points. The number of reported trigger categories was lower at 6 months (p < 0.001), and physical exertion, smoke, irritants, and infection-related ATI domains improved longitudinally. Complete clinical remission was achieved in 5/22 patients (22.7%). Conclusions: Tezepelumab was associated with reduced exacerbations, improved asthma control, and lower patient-reported trigger burden. Structured trigger profiling may provide an exploratory patient-centered dimension for assessing treatment response in severe asthma. 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: 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 and Clinical Significance: 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