Thymic carcinoma is a rare, aggressive malignancy with limited treatment options. First-line platinum-based chemotherapy yields response rates below 40%, and immune checkpoint inhibitors have shown inconsistent efficacy. Ivonescimab, a programmed cell death protein 1/vascular endothelial growth factor (PD-1/VEGF) bispecific antibody, may enhance antitumor activity through dual blockade.This single-center, phase II trial enrolled patients with stage IVb, treatment-naïve thymic carcinoma. Patients received ivonescimab (20 mg/kg) plus paclitaxel (175 mg/m²) and carboplatin (area under the curve 5) every 3 weeks for four to six cycles, followed by ivonescimab maintenance. The primary endpoint was objective response rate (ORR) . Secondary endpoints included disease control rate (DCR) and safety. Biomarker analyses were exploratory.Between January 2025 and April 2026, seven patients were enrolled (median age 61 years; 71% male; 71% squamous). Five had evaluable tissue next-generation sequencing and six had transcriptomic data. After median follow-up of 6.4 months, the preliminary ORR was 85.7% (6/7; 95% CI 42.1% to 99.6%) and DCR 100%. The 6-month progression-free survival (PFS) and overall survival (OS) rates were both 100% (two and four patients at risk for PFS and OS, respectively). The only PFS event occurred at 15.7 months in a patient who discontinued treatment due to adverse events (AEs). Grade ≥3 treatment-related AEs occurred in 57.1% (mainly neutropenia, 42.9%); grade ≥3 immune-related AEs in 14.3%. No treatment-related deaths occurred. All tumors were microsatellite-stable with low mutational burden. Deep responders (≥50% reduction) showed a lower exploratory myeloid-derived suppressor cell-related gene-expression score (nominal p=0.10, exact Mann-Whitney U test). Baseline blood CD4⁺/CD8⁺ ratio was lower in deep responders and remained stable during treatment, vs an increase in others (nominal p=0.057). Tumorous CXCL1 expression showed an exploratory positive correlation with the CD4⁺/CD8⁺ ratio (R=0.84, nominal p=0.035, n=6).First-line ivonescimab plus paclitaxel-carboplatin showed promising preliminary antitumor activity and manageable safety in advanced thymic carcinoma. The peripheral blood CD4⁺/CD8⁺ ratio showed an exploratory association with depth of response and warrants prospective evaluation in the complete cohort and independent validation.Trial registration numberChiCTR2400094398.

To describe the clinicopathological and immunohistochemical characteristics of adenoid ameloblastoma (AdAM), a rare odontogenic neoplasm recognised as a distinct entity in the 2022 WHO classification, and to highlight the diagnostic challenges associated with its overlapping features.

A retrospective analysis was performed on five cases of AdAM diagnosed between 2021 and 2023 at a tertiary care institution. Clinical presentation, radiographic findings, histopathological features, and immunohistochemical profiles were reviewed and systematically analysed.

All patients presented with painless jaw swelling, with a mean age of 40.8 years and a female-to-male ratio of 4:1. Three lesions involved the posterior mandible and two involved the maxilla. Radiographically, four tumours were radiolucent, whereas one exhibited mixed radiolucent-radiopaque features. Histologically, all cases demonstrated characteristic pseudoductal and cribriform patterns with whorled epithelial formations. Additional findings included clear cells, dentinoid deposition, spindle cell areas, ghost cells, and keratin pearl formation. Immunohistochemically, al tumours were positive for AE1/AE3, CK5/6, CK14, and CK19 and negative for CK7. The Ki-67 proliferation index ranged from 2% to 30%, with low-level p53 expression in all cases. One tumour showed BRAF V600E positivity.

AdAM represents a distinct but diagnostically challenging odontogenic tumour with locally aggressive behaviour and potential for recurrence. Recognition of its characteristic histopathological patterns, supported by immunohistochemical findings, is critical for accurate diagnosis and appropriate therapeutic management.

Aortic body tumours are uncommon heart-base neoplasms in dogs, and intracardiac extension causing clinically significant right atrial obstruction is rarely described.

A 7-year-1-month-old, 15.2-kg, castrated male French Bulldog was evaluated for 2 weeks of lethargy, hyporexia, exercise intolerance, abdominal distension, and polydipsia. Transthoracic echocardiography revealed severe right-sided cardiac enlargement and a heterogeneous right atrial intracavitary mass (3.2 × 3.1 cm) suspected to arise from the heart base, with tricuspid regurgitation (maximal velocity 4.03 m/s). Abdominal ultrasonography showed hepatic venous congestion and marked ascites; fluid was a modified transudate. Medical therapy failed to resolve ascites, and surgical debulking was performed on Day 7 under partial cardiopulmonary bypass. The mass was firmly adherent to the atrial septal aspect and could not be completely excised. Postoperatively, ascites and clinical signs resolved, right-sided cardiac enlargement decreased, and tricuspid regurgitation was no longer detectable; the dog was discharged on Day 14. A recurrent right atrial mass was documented on Day 360 without recurrence of right-sided heart failure. The dog died on Day 390 from pancreatitis-associated biliary obstruction and multiple organ failure. Necropsy confirmed an aortic body tumour with intracardiac extension into the right atrium and pulmonary metastasis with tumour emboli.

Partial cardiopulmonary bypass-assisted palliative debulking may temporarily relieve life-limiting intracardiac obstruction in carefully selected dogs; however, this approach is high-risk and non-curative, and its contribution to long-term survival remains uncertain because postoperative toceranib therapy and the natural behaviour of the tumour may also have influenced the clinical course.

Intracranial mesenchymal tumours with in-frame gene fusions of the FET family of RNA-binding proteins to the cyclic AMP response element-binding protein family of transcription factors are exceptionally rare primary central nervous system neoplasms, with morphological similarities to angiomatoid fibrous histiocytoma. Despite their recent inclusion in the 2021 World Health Organisation classification of tumours of the central nervous system, only a limited number of cases have been reported. We describe two cases of intracranial mesenchymal tumours harbouring fusion of the Ewing sarcoma breakpoint region 1 gene with the activating transcription factor 1 gene, both arising from the falx cerebri. Clinical, radiological, pathological, molecular, and therapeutic findings are detailed. A literature review was performed to contextualize our observations. Case 1 involved a 32-year-old man with a parafalcine lesion initially mimicking meningioma, treated with subtotal resection followed by adjuvant radiotherapy. Case 2 concerned a 69-year-old woman with a similar lesion, managed with gross total resection and radiotherapy. Histopathology in both cases revealed epithelioid morphology within myxoid or fibrous stroma, with desmin, epithelial membrane antigen, and CD99 positivity. Molecular analyses confirmed fusion of the Ewing sarcoma breakpoint region 1 gene with the activating transcription factor 1 gene. After 38 and 30 months of follow-up, respectively, both patients remained recurrence-free. These cases reinforce the recognition of intracranial mesenchymal tumours with gene fusions of the FET family of RNA-binding proteins to the cyclic AMP response element-binding protein family of transcription factors as a distinct entity. Accurate diagnosis requires combined histopathological and molecular evaluation. While gross total resection remains the preferred approach, adjuvant radiotherapy may improve disease control. Larger multicentre studies are needed to refine prognostic factors and therapeutic recommendations.

Stuve-Wiedemann syndrome is a rare autosomal recessive bent-bone dysplasia characterized by dysautonomia and distinctive skeletal abnormalities, most commonly caused by biallelic LIFR variants.

Eleven patients from ten unrelated families with molecularly confirmed Stuve-Wiedemann syndrome were evaluated. Detailed demographic, perinatal, clinical, radiographic, and molecular data were collected. All patients underwent Sanger sequencing of LIFR.

Respiratory problems and episodic hyperthermia were present in all patients, while feeding difficulties, hypotonia, growth failure, developmental delay, craniofacial dysmorphism, oral abnormalities, and ocular involvement were also common. All patients demonstrated long-bone bowing, cortical thickening, and flared metaphyses. A biallelic LIFR variant was identified in all patients, occurring in the homozygous state in nine patients and in the compound heterozygous state in two patients. The recurrent c.2074C>T; p.(Arg692Ter) variant was homozygous in seven patients and compound heterozygous in one patient. Three novel LIFR variants were also identified.

Stuve-Wiedemann syndrome is characterized by a high mortality rate during the first two years of life due to severe dysautonomia, and orthopedic complications worsen progressively with age; therefore, early diagnosis and lifelong multidisciplinary follow-up are essential. Furthermore, the high rate of consanguinity in Türkiye, together with the recurrent p.(Arg692Ter) variant in LIFR identified in multiple unrelated families, supports the possibility of a founder effect and suggests that the frequency of Stuve-Wiedemann syndrome in our population may be higher than expected. Our findings further characterize the previously reported clinical manifestations of Stuve-Wiedemann syndrome while expanding the molecular spectrum through the identification of three novel LIFR variants.

Patients with refractory pancreatic cancer have limited therapeutic option and dismal prognoses. This study aimed to evaluate the efficacy and safety of trifluridine/tipiracil (FTD/TPI) in patients with fluoropyrimidine-refractory pancreatic cancer and their predictive biomarkers.

In this single-arm phase II clinical trial, patients of refractory pancreatic cancer were enrolled and administered with FTD/TPI on days 1-5 and 8-12 of a 28-day cycle. The primary end point was the 16-week progression-free survival (PFS) rate. Secondary end points included median PFS, median overall survival (OS), disease control rate (DCR), and toxicities. Clinical and proteomic biomarkers were assessed before treatment and correlated with PFS and OS.

Between March 2021 and June 2023, a total of 28 patients were enrolled. The median age was 64 years (range, 49-80), and 16 (57.1%) patients were male. All patients (100%) received prior fluoropyrimidine. Twenty-three patients (82.1%) received two or more lines of chemotherapy. After a median follow-up of 4.8 months, the 16-week PFS rate was 35.7% (95% CI, 17.8 to 53.2). The median PFS was 3.3 months (95% CI, 1.8 to 4.8) and the median OS was 4.6 months (95% CI, 3.8 to 5.4). The DCR was 50% (14/28; 95% CI, 30.7 to 69.4). The most common grade 3 or worse adverse events were neutropenia (n = 9, 32.1%) and anemia (n = 4, 14.3%) without new safety signals. Neutrophil-to-lymphocyte ratio (NLR) > 5 and high IL1RL1 level were poor prognostic factors, while high APOA4, MSTN, and LUM levels were associated with better prognoses.

To our knowledge, this is the first prospective study to suggest the potential efficacy and acceptable safety of FTD/TPI in patients with pancreatic cancer refractory to fluoropyrimidine. Further randomized trials are needed to validate these findings. NLR, IL1RL1, APOA4, MSTN, and LUM levels are promising biomarkers that warrant further investigation.

Adrenocortical carcinoma (ACC) is a rare and highly aggressive endocrine malignancy with limited treatment options and poor prognosis. Venous tumor thrombus (VTT) is a common complication associated with ACC progression, yet the cellular and molecular mechanisms driving VTT formation remain largely unknown. We performed integrated single-cell RNA sequencing and spatial transcriptomics on paired samples of primary tumor, VTT tail, and VTT head obtained from one ACC patient, followed by in vitro and in vivo functional validation. Our results identified a distinct CD74⁺ tumor cell subcluster enriched in the VTT head region, and functional assays demonstrated that CD74 significantly enhances ACC cell migration, invasion, and proliferation through activation of the JAK-STAT signaling pathway. Moreover, spatial and ligand-receptor analyses revealed that SPP1⁺ macrophages closely interact with CD74⁺ tumor cells via the SPP1-CD44 axis. Functional experiments confirmed that SPP1 secreted by macrophages potentiates CD74-induced JAK-STAT activation and malignant phenotypes. Collectively, we found that CD74⁺ tumor cells drive ACC progression under the regulation of the SPP1-CD44 signaling pathway in the vicinity of SPP1⁺ macrophages, thereby revealing a novel mechanistic axis with therapeutic potential.

Surgical treatment for pulmonary aspergillosis remains technically demanding because of dense pleural adhesions, chronic inflammation, and the risk of major bleeding. We evaluated temporal changes in patient characteristics, perioperative management, and surgical outcomes over a 30-year period at a single institution.

We retrospectively reviewed 57 consecutive patients who underwent surgery for pulmonary aspergillosis between 1992 and 2023. Patients were divided into an early era (1992-2007, n = 23) and a late era (2008-2023, n = 34). Clinicopathological characteristics, operative variables, perioperative management, and postoperative outcomes were compared.

Hemoptysis or bloody sputum and previous pulmonary tuberculosis were significantly less frequent in the late era. Lobectomy was the most common procedure, while video-assisted thoracoscopic surgery was introduced during the later period. Operative time (350 vs. 250 min, p = 0.016) and median blood loss (750 vs. 178 mL, p = 0.003) were significantly reduced in the late era. However, the incidence of major postoperative complications and overall survival did not differ significantly between the 2 eras.

Surgical management of pulmonary aspergillosis has evolved with improvements in operative efficiency and blood loss while maintaining acceptable perioperative and long-term outcomes. Careful patient selection and multidisciplinary perioperative management remain essential, particularly for patients with chronic pulmonary aspergillosis.

The pathogenesis of relapses in patients with microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA) remains ill defined. We aimed to identify whether there are any differences in the molecular profile between patients with relapsing versus new-onset disease.

Whole blood RNA sequencing in 21 patients with MPA or GPA and 12 age-matched/sex-matched healthy controls was performed; 11 patients had active disease, either newly diagnosed (treatment-naïve, n=6) or relapsed (off-therapy, n=5) and 10 were in remission, either on (n=4) or off (n=6) maintenance therapy. Differential gene expression and functional enrichment analysis were conducted.

Relapsing patients with MPA/GPA exhibited a distinct molecular profile compared with healthy controls, newly diagnosed patients or those in remission. Specifically, patients with a major relapse displayed a unique pattern of 41 neutrophil degranulation-associated genes, encoding neutrophil granular proteins, proteins mediating neutrophil adhesion and chemotaxis and proteins involved in myelopoiesis.

In this well-defined MPA/GPA cohort, we report for the first time a distinct relapse-associated transcriptional signature consistent with enhanced neutrophil activity. Therapies targeting neutrophil activation could represent a novel approach for preventing or treating relapses in MPA/GPA.

Little is known about the clinical outcomes of patients admitted to the intensive care unit (ICU) for severe asthma exacerbation requiring ventilatory support.

Our objectives were (i) to describe the initial presentation, therapeutic management and clinical outcomes of adults admitted to the ICU for asthma exacerbation requiring ventilatory support and (ii) to identify risk factors for a prolonged course and/or fatal outcome.

We conducted a 10-year multicentre (n=21) retrospective study in France. All adult patients with asthma admitted to the ICU for an exacerbation requiring invasive (IMV) and/or non-invasive (NIV) mechanical ventilation were included. The primary endpoint was 'complicated course', a composite criterion of death during the ICU stay and/or the need for IMV for ≥7 days.

From 2010 to 2019, 349 patients were included (women 57%, age 54 (40-65) years). Acute respiratory failure was the primary reason for ICU admission. However, 12% of patients were admitted following a cardiorespiratory arrest. Respiratory tract infections were documented in 36% of patients, with Haemophilus influenzae, Streptococcus pneumoniae and Rhinovirus as the predominant pathogens. Three-quarters of the patients required IMV, with a median duration of 5 (3-12) days. One-third underwent NIV as initial ventilatory support, but NIV failed in 23% of them. In-hospital mortality was 8%. The composite primary endpoint was observed in 34% of patients. Multivariable analysis identified Sepsis-related Organ Failure Assessment score, pH≤7.3 and a documented respiratory tract infection on ICU admission as independent risk factors for a complicated course.

Exacerbation requiring ventilatory support was associated with a substantial burden in adult patients with asthma. Respiratory infection was the predominant suspected triggering factor. Respiratory tract infections were documented in 36% of patients and were independently associated with a prolonged course and/or fatal outcome in the ICU.