Chimeric antigen receptor T-cell (CAR-T) therapy has emerged as a transformative immunotherapy, which achieves remarkable success in hematological malignancies. However, broader application of CAR-T therapy is hindered by multiple challenges, including limited efficacy in solid tumors, antigen escape, severe toxicities, and complex, costly manufacturing. Recent studies have emerged that nanotechnology offers innovative solutions to overcome barriers. In this review, we summarized how nanotechnology enhances CAR-T therapy across six dimensions: CAR design, transfection, expansion, modification, monitoring, and combination with other therapies. We discussed the applications of various nanomaterials to improve CAR-T cell function, including lipid nanoparticles, nanogels, and nanobodies. Specifically, we recapitulate that nanotechnology facilitates the generation of CAR-T cells in vivo, enables spatiotemporal control of T cells, remodels the immunosuppressive microenvironment in solid tumors, and enables dual-targeting strategies to mitigate antigen escape. Finally, we outlined the clinical application of nanotechnology in hematological malignancies and solid tumors, as well as non-malignant senescence and autoimmune diseases. Collectively, we believe the integration of nanotechnology enhances the safety and efficacy and broadens therapeutic scope, which will open a new era of precision medicine.

Prolactinomas are the most common functioning pituitary adenomas and can present with a broad spectrum of manifestations. As pituitary adenomas grow insidiously and often result in nonspecific symptoms, diagnostic delay is common. The duration of symptoms first reported by the patient to diagnosis can vary greatly, from patients being diagnosed within one year to over 40 years after symptom onset. Early detection of pituitary adenomas is essential to avoid the accumulation of both hyperprolactinemia and mass effect manifestations, such as visual field loss, infertility, and fatigue among others. Worsening of such manifestations in prolactinomas specifically has an inevitable impact on physical and mental health, comorbid conditions, and quality of life (QOL). Here, we review the literature regarding the prevalence, pathophysiology, and clinical evaluation of presenting manifestations of prolactinomas, discuss contributory factors to diagnostic delay and methods to facilitate earlier identification.

Economic autologous tissue transfer focuses on the efficient use of a patient's own tissues to achieve optimal reconstruction while minimizing donor-site morbidity. Lower limb defects, often resulting from trauma, tumors, or chronic illnesses, present significant challenges in reconstructive surgery due to the need for reliable, functional, and aesthetically acceptable outcomes. This technical note describes the use of the Kiss flap technique to address a chronic tibial bone exposure at the junction of the middle and distal thirds of the leg. Two local perforator-based rotation flaps were harvested and rearranged side by side to achieve defect coverage, utilizing a Doppler pen for precise perforator localization. Postoperative vascularization was confirmed using indocyanine green imaging. The patient achieved complete healing without skin necrosis, with aesthetic improvements including natural hair growth that concealed the scar. The bulkiness of the flap ensured functional outcomes, such as the ability to wear standard clothing comfortably. Compared to traditional options like muscle or free flaps, the Kiss flap offers a reliable, less invasive alternative, particularly in scarred or compromised areas. This case highlights the versatility of the Kiss flap in reconstructive surgery, demonstrating its ability to combine functional and aesthetic outcomes. The integration of advanced vascular mapping and imaging techniques further enhances its precision and reliability, making it a valuable option for lower limb reconstruction.

Thrombocytosis is defined by guidelines as a platelet count of 450 × 103/μL or greater. It most often results from secondary causes and should resolve with treatment of the underlying condition. Primary thrombocytosis in adults is most commonly due to myeloproliferative neoplasms, including essential thrombocythemia. Thrombocytosis may be identified incidentally in asymptomatic patients or when performing blood tests to investigate symptoms or signs that could indicate microvascular conditions (eg, headaches, paresthesia, erythromelalgia), splenomegaly, thrombosis, and hemorrhage, which are presenting features of essential thrombocythemia. A repeat complete blood cell count with differential and peripheral blood smear should be performed to confirm persistent thrombocytosis and assess other blood cell lines for findings suggestive of myeloproliferative neoplasms. Additional testing, including C-reactive protein levels and iron studies with ferritin levels, should be performed based on history and examination findings. If essential thrombocythemia is suspected in patients with persistent thrombocytosis without an identified cause, testing for Janus kinase 2 gene sequence variations should be performed and, if negative, testing for calreticulin and myeloproliferative leukemia gene sequence variations; a bone marrow biopsy should also be performed. The revised International Prognostic Score of Thrombosis for Essential Thrombocythemia should be calculated to stratify thrombosis risk and guide management, including when to use low-dose aspirin and cytoreductive therapy. Cardiovascular risk factors should also be addressed. Hydroxyurea is the first-line agent in cytoreductive therapy. No treatments have been shown to increase survival or prevent progression to myelofibrosis or leukemia in patients with essential thrombocythemia.

This study investigated (pre)clinically the biodistribution of the tri-specific Humabody® CB307, composed of three heavy variable domains (VHs) targeting prostate-specific membrane antigen (PSMA), CD137, and human serum albumin (HSA). CB307 internalization was assessed in PSMA- and CD137-positive tumor and T-cells. In xenograft mouse models bearing PSMA-positive and PSMA-negative tumors biodistribution of 99mTc-PSMA-targeting VHs bound/unbound to mouse serum albumin (MSA) and full-length 99mTc-PSMA monoclonal antibody J591 was assessed by SPECT. Five patients with PSMA-positive metastatic castration-resistant prostate cancer (mCRPC) underwent baseline 18F-PSMA-PET scans to define PSMA-positive lesions, followed by 89Zr-CB307 (37 MBq/5 mg) administration and escalating doses of unlabeled CB307, up to 100 mg. PET was performed at multiple time points. Spherical VOIs were manually drawn around tumors and organs to calculate standardized uptake values (SUVs). Additionally, tumor biopsies were assessed for PSMA expression and autoradiography. CB307 internalized into PSMA- and CD137-positive cells. PSMA-VH x MSA exhibited superior xenograft penetration than unbound PSMA-VH and full-length PSMA-directed antibodies. In patients, no 89Zr-CB307-related adverse events occurred. In the three patients receiving the highest protein dose (5 mg 89Zr-CB307 with 100 mg unlabeled CB307), the geometric mean 89Zr-CB307-SUVmax in all 18F-PSMA-positive lesions increased from 3.53 (day 2) to 4.12 (day 7). Highest uptake was observed in the liver (SUVmean 13.06 ± 2.68 (day 7)), with no significant uptake in the spleen, normal lymph nodes, bone marrow, or salivary glands. Tumor biopsies confirmed radioactivity. 89Zr-CB307 selectively accumulated in PSMA-positive tumor lesions without specific uptake in PSMA-positive-normal or lymphoid tissues in patients with mCRPC.

Peripheral T-cell lymphomas (PTCLs) are heterogeneous neoplasms with poor prognosis and marked geographic variation. Data from Taiwan remain limited. We conducted a 15-year retrospective cohort study of 249 patients diagnosed with PTCL at two major centers in southern Taiwan between 2010 and 2024 to characterize regional epidemiology, real-world treatment patterns, and survival outcomes. The cohort demonstrated subtype distribution typical of East Asia, with nodal T follicular helper cell lymphoma, angioimmunoblastic type (22%), extranodal NK/T-cell lymphoma (21%), and PTCL-NOS (15%) predominating. Most patients presented with high-risk features: 71% Stage III-IV disease, 47% bone marrow involvement, and 64% elevated LDH. Median overall survival was 17.6 months, and event-free survival was 6.4 months. Multivariable analysis identified ECOG performance status ≥ 2, elevated LDH, > 1 extranodal site, and age ≥ 60 years as four independent adverse prognostic factors. Frontline hematopoietic stem cell transplantation (HSCT) showed no significant improvement in outcomes; however, salvage chemotherapy followed by HSCT provided prolonged survival after relapse, with median survival after relapse not reached, compared with 6.1 months with salvage chemotherapy alone. These findings underscore PTCL's persistently poor outcomes and the essential role of salvage HSCT in durable survival. Addressing biological complexity and improving therapeutic strategies remain critical for advancing care. Trial Registration: The authors have confirmed clinical trial registration is not needed for this submission.

NELL-1 (NEL-like protein 1) is a multifunctional secreted glycoprotein that has been implicated in a variety of biological processes, including skeletal development, immune regulation, and tumorigenesis. Despite its significance, the regulatory mechanisms of NELL-1 across different tissues, the diversity of its signaling pathways, and its context-dependent roles in disease are not fully elucidated. This gap in understanding hinders the systematic development and clinical translation of potential applications. Current research suggests that NELL-1 influences skeletal development and regeneration through pathways such as Wnt/β-catenin, MAPK, and Runx3-Indian hedgehog (Ihh). Additionally, it plays crucial roles in conditions such as membranous nephropathy, various tumors, and neurodevelopmental disorders. The distinct isoforms of NELL-1, such as NELL-1570 and NELL-1-ΔE, exhibit specific functional properties and hold significant therapeutic promise, particularly in bone regeneration and tumor suppression. This review aims to provide a comprehensive analysis of the molecular mechanisms of NELL-1 in osteogenesis, chondrogenesis, immune regulation, and tumor suppression. It also explores various strategies to enhance its stability and targeting, including PEG modification and nanoparticle delivery systems. In conclusion, NELL-1 represents a key molecule with multi-tissue, multi-disease regulatory potential, and its value in both basic research and clinical translation is increasingly prominent. Future research should focus on its tissue-specific mechanisms, isoform functional optimization, and the development of safe and effective delivery systems to advance its applications in precision medicine.

Osteochondromas are the most common benign bone tumors, but pelvic involvement is rare. We present a case of an iliac osteochondroma manifesting with atypical hip pain, adding to the limited literature on pelvic osteochondromas and highlighting the diagnostic and management challenges of such cases in an athletic population. A 28-year-old male presented with progressive right greater trochanteric area pain, predominantly nocturnal and exacerbated by running and football but absent during cycling. Physical examination and ultrasound revealed no abnormalities. CT and MRI revealed a pedunculated osseous mass arising from the anterosuperior ilium with cortical and medullary continuity, consistent with osteochondroma. MRI demonstrated a thin cartilage cap (< 2 cm) and local irritation of the iliopsoas. Analgesic therapy, sacroiliac joint injection, and physiotherapy failed to provide relief. After discussion in a multidisciplinary oncology board, the patient underwent en bloc excision. Prognosis was considered favorable given the absence of aggressive imaging features. This case emphasizes that nocturnal hip pain and activity-dependent symptom modulation in a recreational athlete are atypical for the far more common musculotendinous causes of hip pain and should prompt clinicians to consider underlying osseous pathology. Further, it illustrates the importance of multimodality imaging in osteochondromas for accurate characterization and supports the role of multidisciplinary tumor boards in guiding management of rare benign bone tumors.

Meningioma arises from arachnoid cap cells and is a common intracranial neoplasm; however, primary extracranial meningioma is rare, accounting for only 1%-2% of cases and is therefore frequently misdiagnosed. We report a case of primary extracranial meningioma arising in the temporal region without intracranial or dural involvement. A 66-year-old woman presented with a slowly enlarging mass in the left temporal region for approximately 10 years, without pain or limitation of mouth opening. Computed tomography revealed a 2.1× 2.7× 4.6 cm mass between the temporalis muscle and the skull, with no intracranial extension. Fine-needle aspiration suggested a spindle-cell neoplasm, and complete excision was performed via a coronal scalp incision for diagnosis and treatment. Histopathologic and immunohistochemical examination confirmed a World Health Organization grade II extracranial meningioma. The patient recovered without complications. Postoperative magnetic resonance imaging showed no residual tumor, and adjuvant radiotherapy was not administered. Surveillance imaging every 6 months demonstrated no recurrence over 3.5 years. This case highlights the importance of including extracranial meningioma in the differential diagnosis of temporal masses and supports complete excision as effective management. A brief literature review is included.