Our knowledge of water bonding on metal surfaces is ruled by the coexistence of covalent and electrostatic nature in water-metal interactions, which leads to the well-known, preferred flat geometry on transition metal surfaces. Using density functional theory (DFT) calculations, herein we have shown that this picture has to be modified for water bonding on Sc(0001), Y(0001), and La(0001), where upright water orientation has been surprisingly found to preferentially coexist with the flat geometry on the rare-earth metal surfaces. Our investigations have proved that both water orientations on the rare-earth metal surfaces originate from unique bonding mechanisms that do not exist in water adsorption on any late transition metal surfaces. In this unique bonding picture, covalent components are evidently absent in the water-metal interactions, which are overwhelmingly dominated by the first-order quantum electrostatics featured by two nearly separated potential wells in the water-metal bonds and by the second-order quantum electrostatics featured by alternating charge depletion and accumulation regions in interference. The new picture not only advances our understanding of how water makes bonds with earlier transition metal surfaces but also lays a physical basis for improving catalytic performance of the rare-earth-metal-based green catalysts for clean energy.
Pulmonary sarcomatoid carcinoma (PSC) is a rare and highly aggressive form of non-small cell lung cancer. Rectal metastasis of PSC is an extremely rare condition. We herein report a rare case of PSC accompanied by rectal metastasis detected by 18F-FDG PET/CT. This case highlights the diagnostic value of 18F-FDG PET/CT in detecting uncommon metastatic sites in PSC.
Reimbursement decisions for orphan drugs are complex, as conventional cost-effectiveness frameworks may not fully capture broader societal values. To investigate public preferences regarding the inclusion of rare disease drugs in China's Basic Medical Insurance (BMI) using a multi-center discrete choice experiment. From July to September 2024, a face-to-face, filed-based discrete choice experiment (DCE) was conducted across four regions in China. Using non probability sampling technique which is known as Quota sampling, participants evaluated drug profiles varying in six attributes. Mixed logit model and latent class model were used for analysis. Relative importance, willingness to pay (WTP), scenario analysis and preference heterogeneity were estimated. Of the 761 respondents retained after initial data cleaning, 622 passed the internal consistency check and were included in the final analysis. Most participants were urban residents (62.7%), employed (66.6%), and covered by urban and rural resident basic medical insurance (BMI) (57.7%). The general public preferred including orphan drugs in BMI coverage when treatments provided greater health gains, targeted diseases with moderate untreated life expectancy, and lacked existing reimbursed alternatives. In contrast, poorer untreated quality of life and larger increases in BMI financing reduced utility. Health gains were the most important, followed by increases in BMI financing, untreated quality of life, existing BMI coverage, and untreated life expectancy. Annual WTP was ¥1.225 per capita for quality-adjusted life years (QALY) gains (0.01-4), with lower WTP observed among respondents facing poorer untreated quality of life. Scenario analysis showed that 78.5% would support reimbursement for drugs providing maximal health gains (0.01-4). Preference heterogeneity was observed across age, sex, education, household income, insurance type, and urban-rural residence. Latent class analysis identified two subgroups. The "life-saving group" (23%) showed strong preferences for greater disease severity and larger health gains, whereas the "pragmatist group" (77%) demonstrated relatively flatter preferences and negative utility associated with declining untreated life expectancy. While health gains drive preferences, the public also values equity, disease severity and affordability. Policymakers must integrate these multidimensional social values to ensure legitimacy and fairness in allocating finite resources for rare diseases. Members of the public were involved in the development of the DCE. In the attribute development phase, members of the public participated in a pilot study to help ensure the clarity and comprehensibility of attribute descriptions and levels. And their feedback informed revisions to the questionnaire. In the main study, members of the public participated as respondents, providing data on societal preferences for orphan drug reimbursement.
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Intussusception is the telescoping of one bowel segment into another, causing obstruction and ischemia. It is uncommon in adults and is most often associated with an underlying neoplasm. Colonic involvement is less frequent, and arteriovenous malformations (AVMs) represent an unusual etiology, with no previously reported fatal rectosigmoid cases to our knowledge. We describe the case of a 41-year-old man with a medical history of tuberculosis and gastrointestinal disease who suddenly developed severe abdominal pain at home. His condition rapidly deteriorated, and he was transported to the emergency department, where he arrived in cardiac arrest. External examination revealed no signs of trauma. Autopsy showed bilateral pleural effusion and markedly emphysematous lungs. Abdominal examination revealed peritoneal effusion, diffuse bowel wall thickening, and hemorrhagic intraluminal content. A colo-recto-sigmoid intussusception causing near-complete obstruction was identified, with a firm intraluminal mass acting as the lead point. Histopathologic analysis demonstrated a vascular lesion composed of arteries, veins, and capillaries associated with neural hyperplasia, favoring a vascular malformation with AVM-like features. No malignancy was found. This case describes a fatal rectosigmoid intussusception associated with a colonic vascular lesion showing AVM-like features and underscores the importance of considering vascular lesions as potential lead points in adult intussusception.
Spontaneous rupture of primary liver tumors is a well-recognized and potentially life-threatening complication of hepatocellular carcinoma, whereas rupture of metastatic liver tumors is rare. We report the case of a 60-year-old woman with spontaneous rupture of liver metastasis from a mucosal melanoma, a rare subtype of malignant melanoma. Intraperitoneal bleeding was controlled by transcatheter arterial embolization, and liver tumor biopsy confirmed metastatic melanoma. The maxillary sinus was identified as the primary site. Based on the clinical course, the liver metastases appeared over a short period and progressed rapidly. In addition, contrast-enhanced computed tomography (CT) performed immediately before rupture showed overall poor but heterogeneous enhancement of the ruptured tumor, with a tortuous dilated intratumoral vessel penetrating the lesion. Three-dimensional CT angiography reconstructed from this CT dataset demonstrated that the penetrating vessel represented a tumor-feeding artery, which was morphologically more consistent with a pre-existing hepatic vessel altered by tumor progression than with a newly formed tumor neovessel. Although rare, rupture of metastatic liver tumors may be associated with rapid tumor growth. Importantly, a tortuous dilated intratumoral vessel identified on pre-rupture CT may represent an imaging feature associated with tumor fragility and impending rupture.
A rare congenital nasopharyngeal hairy polyp was incidentally identified during an attempted adenoidectomy in a 15-month-old female. The patient presented with snoring and intermittent apnea concerning for upper airway obstruction. Magnetic resonance imaging (MRI) revealed a 2.5-cm partially enhancing nasopharyngeal mass along the soft palate, likely originating near the left nasopharyngeal wall or Eustachian tube orifice. The lesion was excised transorally without complications. Histopathological analysis confirmed a benign hairy polyp composed of mature adipose tissue, skeletal muscle, and cartilage, lined by keratinized squamous epithelium with underlying adnexa including pilosebaceous units. Postoperatively, the patient's symptoms resolved. Interval postoperative MRI surveillance is planned for 6 months. This case highlights the importance of considering rare congenital lesions within the differential diagnosis of pediatric obstructive sleep symptoms. Early recognition and diagnosis can lead to appropriate surgical planning and better outcomes for these patients.
Excess iodine from iodinated contrast media (ICM) can lead to thyroid dysfunction. Children, especially neonates and premature infants, may be more vulnerable due to their immature thyroid physiology. A systematic review was conducted using Embase, Medline (PubMed), Cochrane, Web of Science, and Scopus. Inclusion criteria were studies in children ≤18 years receiving ICM and that reported effects on thyroid function. Exclusion criteria included topical iodine exposure, prenatal administration, and irrelevant endpoints. Case reports, reviews and abstracts were also excluded. Most studies reported temporary thyroid function disturbances following ICM in children, particularly subclinical hypothyroidism. Overt hypothyroidism was rare and occurred mainly in neonates and high-risk groups. In certain studies, up to 25% of neonates showed TSH abnormalities, with a subset requiring levothyroxine treatment. Although even more rare, some studies also reported cases of thyrotoxicosis after ICM. ICM exposure can lead to thyroid dysfunction in children, especially in neonates, preterm infants, and those with risk factors. Risk-based screening and monitoring are recommended to allow timely detection and treatment.
To alert clinicians to the risk of severe hypercalcemia arising from the ATRA-azole interaction and to highlight a rare diagnostic pitfall involving a false-positive cerebrospinal fluid (CSF) (1,3)-β-D-glucan (BDG) result. Concurrent use of all-trans retinoic acid (ATRA) and azole antifungals poses a risk of severe hypercalcemia in pediatric acute promyelocytic leukemia (APL). We performed a retrospective clinical and laboratory review of two 10-year-old patients with APL who developed drug-induced toxicity during induction therapy. Both patients developed severe hypercalcemia induced by ATRA combined with fluconazole or voriconazole, presenting with intractable vomiting and headache. Notably, one case was confounded by an elevated CSF (1,3)-β-D-glucan level (a false-positive laboratory artifact), which mimicked fungal meningitis and delayed the correct diagnosis. Clinicians must remain vigilant for ATRA-associated hypercalcemia during azole co-administration. Recognizing diagnostic mimics and implementing routine calcium monitoring are crucial to prevent misdiagnosis and severe toxicity.
Immunodeficiency, centromeric instability, facial anomalies (ICF) syndrome is a rare autosomal recessive disorder characterized by immunodeficiency, centromeric instability, and facial dysmorphism. We report four Chinese pediatric patients with ICF syndrome diagnosed between 2018 and 2021. All patients presented with recurrent infections due to hypogammaglobulinemia. Whole-exome sequencing identified four novel mutations: CDCA7 c.695delC (p. Val233Ter), HELLS c.560T>G (p.L187W), ZBTB24 compound heterozygous (c.1228_1229delinsC and c.649_652del), and ZBTB24 homozygous (c.1208A>G, p.H403R). To our knowledge, this is the first report of CDCA7 p. Val233Ter and HELLS p.L187W mutations globally. These findings expand the mutational spectrum of ICF syndrome.
A dual imaging pattern of hyperattenuation on non-enhanced computed tomography and hypointensity on T2-weighted imaging is frequently encountered in various lesions. In the present review, we aimed to explore this imaging combination across a spectrum of abdominal and pelvic lesions to clarify its clinical implications.This pattern is commonly observed in lesions rich in fibrous or smooth muscle components, making it more frequently encountered in benign entities, including fat-poor angiomyolipomas, uterine leiomyomas, and tumors with predominant fibrous stroma. However, similar imaging findings may also be encountered in rare high-cellularity malignancies, selected systemic diseases, and lesions containing melanin, metal deposition, or thyroid tissue. Although not specific to a single disease, this imaging pattern offers valuable diagnostic clues for lesion characterization. When contrast-enhanced imaging is unavailable or contraindicated, combining non-enhanced computed tomography and T2-weighted imaging findings may help narrow the differential diagnosis. Despite its general association with benign lesions, this imaging phenotype requires careful exclusion of important pathologic mimics. Overall, integration with clinical information and other imaging findings remains essential for accurate interpretation.
Visual impairment due to optic chiasm compression is a frequent complication of pituitary macroadenomas and substantially impacts quality of life. Reported postoperative visual field (VF) results after endoscopic endonasal transsphenoidal surgery (EETS) vary across series. We performed a single-arm meta-analysis to quantify postoperative VF outcomes after EETS for pituitary macroadenomas. PubMed/MEDLINE, Scopus, and Web of Science were searched in accordance with PRISMA through September 2025. Eligible studies were prospective or retrospective clinical series of pituitary macroadenomas (≥ 5 patients) undergoing EETS with extractable postoperative VF outcomes. Pooled proportions for VF improvement, normalization, stability, deterioration, and cerebrospinal fluid (CSF) leak were calculated using random-effects models with Freeman-Tukey double-arcsine transformation. Heterogeneity was assessed using I2 and prediction intervals were reported. Twenty nine studies involving 2,943 patients met criteria. Across studies, the combined rate of postoperative VF improvement was 79% (95% CI: 73-84%), while normalization was achieved in 41% (95% CI: 29-53%). VFs remained unchanged in 19% (95% CI: 14-25%) of patients, and deterioration following surgery was infrequent (1%; 95% CI: 0-1%). The pooled postoperative CSF leak rate was 7% (95% CI: 4-10%). In pooled single-arm data, EETS for pituitary macroadenomas is associated with high rates of VF improvement and rare postoperative deterioration. Because VF testing and follow-up were heterogeneous across studies, these pooled results should be interpreted as benchmark outcome rates rather than standardized recovery "patterns." Standardized VF reporting is needed to enable stronger prognostic and time-course analyses.
Nemaline myopathy type 6 (NEM6) is a rare neuromuscular disorder caused by pathogenic variants in the Kelch repeat and BTB domain-containing 13 (KBTBD13) gene. Patients experience muscle weakness, excessive fatigue, and impaired muscle relaxation that affect their daily activities related to abnormal protein aggregation in muscle cells and a predominance of slow-twitch myofibers, and no specific therapies are available. Here, we studied a clinically relevant Kbtbd13:p.Arg408Cys knockin mouse model to elucidate the molecular changes driving disease pathogenesis through measurements of muscle contractility, single myofiber assays, super-resolution microscopy, and x-ray diffraction. Kbtbd13:p.Arg408Cys knockin mice closely phenocopied human NEM6 pathology at the morphological, functional, and transcriptional levels, with the p.Arg408Cys variant causing mislocalization of KBTBD13 in the muscle sarcomere, associated with disease onset between 1 and 3 months of age, plateauing by 9 months, and with little progression at 18 months. As a potential therapeutic approach, we knocked down Kbtbd13 using short hairpin RNA against Kbtbd13 delivered intramuscularly via an adeno-associated virus 9 vector at either the prephenotype (1-month-old) or peak-phenotype (3- or 7-month-old) stages. A single treatment at the prephenotype stage prevented the development of impaired relaxation kinetics, nemaline rod aggregation, and slow-twitch myofiber predominance at 3 months of age. A single treatment at 3 months of age, after onset of disease, restored muscle morphology, contractility, and muscle-relaxation kinetics over 6 months. These data provide insights into NEM6 pathogenesis and suggest that Kbtbd13 knockdown might be a promising therapeutic strategy for patients with NEM6.
Aneurysmal bone cyst (ABC) is a benign but locally aggressive osteolytic lesion that predominantly affects children and adolescents. Foot involvement is uncommon, with metatarsal lesions representing a rare subset. Reconstruction of the first metatarsal is particularly demanding due to its critical biomechanical role in forefoot load transmission and push-off during gait. A 17-year-old male presented with right forefoot pain after trauma and was found to have a pathological fracture through an expansile lytic lesion of the first metatarsal. Initial conservative management was followed by clinical deterioration. Imaging revealed a 30 × 47 × 30 mm multiloculated lesion with fluid-fluid levels. Biopsy confirmed aneurysmal bone cyst. The patient underwent en bloc resection and reconstruction using an ipsilateral fibular strut autograft. Fixation was achieved using a joint-preserving dual plate construct assisted by a distal mini-fragment plate. At 9 months, the patient demonstrated radiographic union, preservation of first-ray alignment, and no recurrence. Functional outcome improved significantly, with the AOFAS score increasing from 39% preoperatively to 90% postoperatively. Fibular strut graft reconstruction for metatarsal ABC is established in the literature. This case highlights a fixation refinement using mini-fragment-assisted dual plating to enhance distal fixation while preserving the first metatarsophalangeal joint. This technique may represent a viable option in selected cases.
Establishing causality in nutritional science is difficult. Human diets are complex, and individuals vary substantially in how they respond to dietary exposures. The nutrition literature mostly relies on observational studies, which are vulnerable to confounding and measurement error. Twin-based randomized controlled trials (RCTs), especially the co-twin control design, offer a compelling methodological solution to many of these challenges. This design enables researchers to distinguish genetic from environmental influences on health outcomes. The present scoping review was conducted to systematically map twin RCTs in nutrition science, evaluate their methodological approaches, and identify gaps and opportunities for future research. A comprehensive search across clinical trial registries and electronic databases yielded only 13 eligible studies, demonstrating that co-twin randomized dietary interventions remain rare relative to standard study designs using nontwins or twins assigned to the same arm. The interventions used in these eligible RCTs could be classified into four groups: dietary pattern interventions, nutrient- or supplement-based interventions, dietary component modification, and behavioral or multimodal interventions. This limited number of studies may be explained by recruitment challenges and concerns about generalizability. Greater international collaboration, standardized trial protocols, and integration of emerging technologies could expand the utility of twin designs in nutrition science.
We present two cases of Evans syndrome (ES) during durvalumab monotherapy after combination chemotherapy with durvalumab for advanced hilar cholangiocarcinoma. The patients were men aged 71 and 73 years with satisfactory performance status. They received eight cycles of gemcitabine, cisplatin, and durvalumab, followed by durvalumab monotherapy (five and six cycles, respectively) for a total of approximately 11 months. Subsequently, they developed autoimmune hemolytic anemia, characterized by reticulocytosis, indirect hyperbilirubinemia, elevated lactate dehydrogenase levels, and a positive direct Coombs test. Furthermore, their condition met the diagnostic criteria for ES, as they developed concomitant thrombocytopenia with antiplatelet antibodies. Both patients demonstrated hematological recovery with corticosteroid therapy, highlighting the efficacy of immunosuppression in managing this rare hematologic immune-related adverse event. Notably, the onset occurred during maintenance therapy after a prolonged latency of 11 months, underscoring the potential for delayed hematologic immune-related adverse events with programmed death-ligand 1 blockade. Corticosteroids remain the cornerstone of treatment, and high-dose pulse therapy may be necessary in refractory cases. In conclusion, recognition of durvalumab-induced ES is crucial for appropriate management.
Gluteal fat grafting is associated with rare but potentially fatal complications, particularly fat embolism related to inadvertent intramuscular injection. Current safety recommendations emphasize strict subcutaneous fat placement. Intraoperative ultrasound has been proposed as a tool to enhance procedural safety; however, the extent and quality of supporting evidence remains unclear. A scoping review was conducted according to PRISMA-ScR and Joanna Briggs Institute methodology. Six electronic databases were searched from the earliest available records through March 2025. Studies including adult patients undergoing ultrasound-guided gluteal fat grafting were eligible. Nine studies published between 2018 and 2025 met inclusion criteria. Evidence consisted predominantly of observational case series and one systematic review with meta-analysis; no randomized or high-quality comparative studies were identified. Ultrasound was primarily used to guide cannula positioning and confirm subcutaneous fat injection in real time. Verification of the injection plane relied mainly on intraoperative visualization rather than standardized imaging-based confirmation. No cases of fat embolism or procedure-related mortality were reported. Additional procedural benefits were described but were largely qualitative and infrequently assessed using comparative outcome measures. Intraoperative ultrasound appears to be a useful safety adjunct in gluteal fat grafting; however, current evidence is limited and primarily non-comparative. Further comparative studies are required to establish its clinical benefit.
Myxoid epithelioid sarcoma is a rare morphologic variant of epithelioid sarcoma characterized by abundant myxoid stroma and frequent loss of SMARCB1/INI1 expression. Orbital involvement is exceptionally uncommon. We report a case of a SMARCB1-deficient malignant orbital neoplasm with features overlapping myxoid epithelioid sarcoma in a 61-year-old man presenting with visual disturbance. Imaging studies revealed a 2.5-cm medial orbital mass without evidence of another primary lesion. The tumor was excised without prior biopsy. Histologically, the lesion was predominantly composed of abundant myxoid stroma containing scattered atypical epithelioid, signet ring-like, and spindle cells, with focal fascicular proliferation infiltrating skeletal muscle. Immunohistochemically, tumor cells were positive for pan-cytokeratin, EMA, vimentin, and CD34, while negative for S100, ΔNp63 (p40), p63, SS18-SSX, and TLE1. Complete loss of SMARCB1/INI1 expression was observed in tumor cells. The overall findings suggested a SMARCB1-deficient malignant neoplasm showing substantial morphologic and immunophenotypic overlap with myxoid epithelioid sarcoma. This case highlights the diagnostic challenges posed by SMARCB1-deficient tumors arising in unusual anatomical sites and expands the clinicopathological spectrum of myxoid epithelioid sarcoma-like neoplasms involving the orbit.
Pediatric membranous nephropathy (MN) is a rare glomerular disease with limited data available. This single-center study aims to describe risk stratification-based treatment and its outcomes. This retrospective observational study included children younger than 18 years of age with primary MN diagnosed from July, 2021 to December, 2024. KDIGO risk stratification criteria were modified with author consensus for pediatric thresholds, and children were stratified into low, moderate, high and very high risk. Immunosuppressive drugs included calcineurin inhibitors (CNIs), cyclophosphamide (CYC) and rituximab (RTX). Outcomes included complete remission, partial remission, no response, relapse, and decline in kidney function at 12 months and last follow-up, and were summarized across baseline risk categories and initial treatment groups. Time to first complete or partial remission was assessed using Kaplan-Meier analysis and compared using the log-rank test. Thirty-three children were included with a mean age of 11.15 ± 3.16 years, of whom 24 (73%) were males. Baseline risk stratification showed 24 (73%) were in the high-risk category. Initially, CNIs were administered in 17 (51.5%), while CYC and RTX in 5 (15%) and 3 (9%) patients, respectively. Among high-risk patients, non-response was observed in 8 (34%) at 12 months and 4 (17%) at last follow-up. Anti-PLA2R positivity was associated with better outcomes, with higher rates of complete or partial remission (p = 0.03). At last follow-up, 4 (12.1%) children demonstrated decline in kidney function. We describe treatment allocation and short-term outcomes in pediatric MN using a modified risk stratification-based approach. Higher risk categories appeared to have less favorable responses, while anti-PLA2R positivity was associated with better outcomes.
Intraventricular schwannomas are exceptionally rare; fewer than fifty cases have been documented since 1957. We report an adolescent case with massive cystic degeneration and chronic intratumoural haemorrhage, and synthesise the current literature. Clinical, radiological, operative, and histopathological data for a 16-year-old male were collected prospectively. A targeted literature review (1957-2025) was performed. To ensure diagnostic accuracy, imaging characteristics were analysed exclusively in cases with documented CT or MRI findings. A 16-year-old male presented with headache and left-arm tremor. CT/MRI demonstrated a 9.2 cm cystic, haemorrhagic mass in the right lateral ventricle. Gross-total resection was achieved; histology confirmed benign schwannoma (Ki-67 5%). A review of 46 cases (mean age 33.4 years; 63% ≤ 40 years; 65% male) revealed 95.7% had benign histology, and 74% of cases underwent gross-total excision, with no recurrence at a mean follow-up of 32 months. Among them, 42 cases had detailed CT/MRI data available; in this subgroup, 17 (40.5%) showed cystic degeneration, and 13 (31.0%) showed haemorrhage.  Chronic haemorrhage and massive cystic degeneration can obscure the diagnosis of intraventricular schwannoma. Although these features may mimic malignant ventricular neoplasms, identifying specific signs such as haemosiderin deposition may provide critical clues for differential diagnosis. Accurate diagnosis requires clinico-radiological-pathological correlation. Complete microsurgical excision offers an excellent prognosis; however, elevated Ki-67 index warrants vigilant surveillance.