Search Results (4,891)

Background: Photothermal therapy (PTT), a highly efficient and controllable method with minimal drug resistance, transforms near-infrared (NIR) radiation into heat. This process exerts antibacterial effects, aids in tissue repair, and promotes healing. Methods: Our study presented a novel kind of composite wound dressing that incorporated adhesive conductive hydrogel combined with piezoelectric film for NIR-responsive applications. The inherent adhesiveness of the hydrogel ensured robust anchoring of the piezoelectric film to both hydrogel matrix and wound site. Its conductivity enabled synergistic endogenous electrical stimulation with the piezoelectric film, while also serving as therapeutic layer to augment hemostasis, analgesia, and antibacterial activity. Results: The hydrogel’s capacity for moisture retention and exudate absorption sustained optimal wound environment, thereby supporting debridement and recovery. Furthermore, the piezoelectric film possessed excellent photothermal properties and transferred heat to the hydrogel through heat conduction to enhance antibacterial activity and promote wound healing. The in vitro and ins vivo experiments confirmed that the composite dressing exhibited strong promotion effect on wound healing under NIR irradiation. Conclusions: In summary, our research provided a new strategy for developing advanced piezoelectric biomaterials with great clinical potential for wound healing. Full article

Background: Intestinal acute radiation syndrome (IARS) represents a life-threatening component of acute radiation syndrome with limited effective countermeasures. Understanding molecular determinants governing intestinal epithelial resilience to ionizing radiation is critical for developing radiation toxicity mitigation strategies. Objectives: This study investigates the role of PIKfyve, a phosphoinositide kinase essential for endolysosomal homeostasis, in modulating radiation-induced intestinal toxicity. Methods: We utilized an inducible intestinal epithelial-specific PIKfyve-knockout mouse model (PIKfyve cKO) subjected to 10 Gy abdominal irradiation. Intestinal toxicity was assessed through histopathology, barrier permeability (FD4 assay), apoptosis markers, and transcriptomic profiling. Small intestinal organoids were employed for mechanistic validation. Results: PIKfyve deletion alone did not perturb normal gut architecture but precipitated severe post-irradiation toxicity, including villous atrophy, crypt hypoplasia, and massive crypt-cell apoptosis. Barrier dysfunction was evidenced by elevated serum FD4 and heightened systemic pro-inflammatory cytokines, culminating in markedly increased mortality. Transcriptomic analysis revealed potentiated DNA-damage signaling and amplified inflammatory cascades in PIKfyve-deficient intestines. Conclusions: These findings identify PIKfyve as a critical guardian of intestinal epithelial integrity against radiation toxicity. Given emerging PIKfyve inhibitors in cancer therapy, our results raise important safety considerations for clinical radiotherapy and position PIKfyve as a potential target for radiation toxicity mitigation. Full article

Fanconi anemia (FA) is a rare inherited disorder associated with impaired DNA repair, characterized by congenital anomalies, bone marrow failure, and a significantly increased risk of developing malignancies, particularly squamous cell carcinoma (SCC) of the head and neck. Treatment options for advanced SCC in FA are limited due to hypersensitivity to DNA-damaging agents. This article presents a unique case of SCC that developed in a 17-year-old patient with FA caused by a homozygous mutation in the FANCA gene. At the age of 10, he received a bone marrow transplant from a compatible related donor. Conditioning therapy included busulfan, thymoglobulin, and fludarabine, while graft-versus-host disease (GvHD) prophylaxis was administered with rituximab, methotrexate, and cyclosporine A. Nevertheless, he developed chronic cutaneous GVHD, which was treated for four years with ruxolitinib and tacrolimus, achieving only partial control. During this period, locally advanced cutaneous SCC (T3N0M0, stage III) manifested on the face. Surgery, radiation therapy, and immunotherapy with pembrolizumab led only to an initial partial response. This first pediatric case of immunotherapy for SCC in FA highlights the challenges of treating this rare patient group. Nevertheless, combining radiation therapy with immunotherapy may represent a possible option for disease control. Full article

Spinal infections in general, and infectious spondylodiscitis in particular, are increasingly diagnosed in the Western world, in recent decades. This rise in incidence is associated with an ageing population and with an increased availability of accurate diagnostic modalities. Even so, due to the non-specific nature of clinical manifestations, and of the implicated blood and serum markers, there is a risk of underdiagnosis or misdiagnosis of the disease in its initial stages. Ionizing radiation methods, such as plain radiography (X-ray) and computed tomography (CT), are also not reliable in the early stages of the diseases, and the golden standard of imagistic diagnosis, magnetic resonance imaging (MRI), is not always available or requested. Still, MRI remains the most reliable method in most cases where there is a need for differential diagnosis with other pathologies, namely Andersson lesions, destructive spondyloarthropathy, erosive osteochondritis, micro-crystalline spondylitis, Modic 1 lesion, Charcot spinal arthropathy, osteoporotic fractures, SAPHO syndrome with spinal involvement, and Schmorl’s nodes. Infectious spondylodiscitis is caused by bacteria, and, less frequently, by fungi. Rare cases of parasitic causes have also been reported in the literature. Infectious spondylodiscitis of bacterial causes may be pyogenic, more frequently caused by Staphylococcus spp. or Streptococcus spp., or granulomatous, usually caused by Mycobacterium tuberculosis complex (MTBC) or from classical brucellosis. In all these cases, therapy may be conservative, with antibiotics, or surgical, when the former fails or in patients with significant spinal instability or other neurological manifestations. There are various surgical approaches, each with its own drawbacks, and usually used according to the preference of the attending physician. Even in cases of surgical treatment, antibiotic administration is prolonged, and it is important for a proper scheme to be selected based on antimicrobial susceptibility testing. However, given that in many cases, the causative agent cannot be identified, empirical treatment must be initiated. Finally, newer approaches, including the incorporation of antimicrobial substances, may offer better solutions for improving treatment and rehabilitation outcomes. Full article

Background/Objectives: Stage III non-small cell lung cancer (NSCLC) is a heterogeneous and clinically challenging disease. Despite therapeutic advances, decisions regarding resectability and treatment sequencing remain complex. Multidisciplinary discussion (MDD) is increasingly recognized as key to personalized, evidence-based care. Methods: The “Integrate 6.0” conference gathered approximately 90 lung cancer specialists, including oncologists, thoracic surgeons, and radiation oncologists, divided into mixed groups simulating multidisciplinary team (MDT) meetings. Groups reviewed complex clinical cases, supported by facilitators providing concise, evidence-based updates. A pre-event survey explored MDT structure and dynamics across institutions. Results: The survey highlighted considerable variability in MDT composition and practices. Most participants had significant involvement in thoracic oncology. Discussions revealed higher consensus in straightforward cases, while complex stage III scenarios—especially with driver mutations or bulky nodal disease—required more nuanced, collaborative decision making. Key topics included neoadjuvant chemoimmunotherapy, surgery in borderline resectable cases, and managing immune-related toxicities. Conclusions: “Integrate 6.0” effectively connected theoretical knowledge with real-world practice through interactive, multidisciplinary dialogue. It underscored the vital role of MDD in managing complex stage III NSCLC and the need for adaptable treatment strategies. Future conferences should assess MDD’s impact on outcomes and expand participation to include molecular pathologists and geriatricians. Full article

Objectives: To exploratorily evaluate the potential of baseline dedicated breast PET (D-PET) for noninvasive prediction of pathological complete response (pCR) to neoadjuvant chemotherapy (NAC) in HER2-positive (HER2+) breast cancer, and to investigate a fusion strategy integrating conventional radiomics and deep learning features. Methods: We developed a multi-representation framework with radiomics based on data-driven high-/low-uptake metabolic subregions and deep learning trained on standardized 3D tumor volumes, and intratumoral heterogeneity (ITH) was quantified on the largest slice as an additional comparator. The outputs of these pathways were subsequently integrated through feature-level and decision-level fusion. Model performance was evaluated using the area under the receiver operating characteristic curve (AUC), and interpretability analyses were applied to identify image regions and features contributing to predictions. Results: In a HER2-positive breast cancer cohort (n = 147) with baseline D-PET, deep learning (3D ResNet, AUC = 0.79) and radiomics (logistic regression, AUC = 0.78) achieved comparable performance on the primary test set, whereas the ITH model showed limited value (AUC = 0.61). Fusion further improved discrimination on test set 1, with an AUC of 0.83 for decision-level fusion and 0.84 for feature-level fusion. On test set 2, decision-level fusion achieved the highest AUC (0.84), and feature-level fusion maintained stable performance (AUC = 0.80). Conclusions: In this exploratory study, baseline D-PET showed promising performance for noninvasive prediction of NAC response in HER2+ breast cancer. The fusion of deep learning and radiomics yielded improvements over single-representation models, highlighting the potential role of D-PET models as decision-support tools. Full article

Appendicular soft tissue sarcoma (aSTS) is a group of highly heterogeneous tumors of mesenchymal origin for which standard care usually includes surgical resection with or without radiation therapy. The main goal of surgical treatment in aSTS is to achieve wide tumor resection with negative margins while promoting the best function possible for the affected limb. Orthoplastic surgery represents the concept of a multidisciplinary approach comprising a synergistic collaboration between orthopedic and plastic surgeons. The development of this philosophy allows us to push forward the concept of limb salvage surgery for sarcomas, even when dealing with extremely complex cases. Reconstruction techniques integrated with orthoplastic principles range from simple to highly complex surgeries. Vascularized auto- or allo-graft tissue transfers illustrate how far reconstruction options can go, allowing for repair of large soft tissue defects or even restoration of muscle function in key anatomic segments after oncological resection. The reported experience with orthoplastic philosophy in aSTS suggests that it is a feasible and reproducible strategy that can achieve limb salvage rates above 90%, optimal oncologic local control characterized by more than 95% of wide margin resection, and improved functional and esthetic results. Most patients with aSTS treated under orthoplastic principles present good-to-excellent postoperative Musculoskeletal Oncology Society (MSTS) scores, confirming the advantages of this comprehensive approach. While there is significant experience with the orthoplastic approach for trauma cases, the road still needs to be paved for musculoskeletal oncologic reconstruction. Nonetheless, the results are promising and could inspire a wider adoption of structured orthoplastic protocols for sarcoma patient care. Herein, the authors explore the current practice regarding the application of collaborative orthoplastic approaches for the management of appendicular soft tissue sarcomas, reporting on outcomes and elaborating on future trends. Full article

Background/Objectives: Magnetic resonance imaging (MRI) provides a non-invasive means for a comprehensive assessment of the effect of radiation therapy (RT) on heart function. This study aims to determine RT induced cardiotoxicity in thoracic cancer patients using cardiac MRI. Methods: Cardiac MRI was performed at baseline and at six months post-treatment in patients undergoing standard-of-care RT for lung or esophageal cancers at a single institution. Parameters included regional myocardial strain in the longitudinal, circumferential, and radial directions as well as myocardium T1, T2, and extracellular-volume (ECV) maps. Cardiac segmental doses were extracted from the RT planning scans. The relationship between changes in segmental MRI parameters at six months and segmental heart RT dose were investigated. Results: Twelve patients underwent baseline MRI and four completed the follow-up MRI. Five of the segmental strain parameters showed notable changes between baseline and six-month follow-up. Increased doses in the heart base and apex were associated with moderate-to-large and mild deteriorations, respectively, in strain for all regions. Increased doses in the mid-ventricular regions were associated with improved strain in all regions. The segmental analysis revealed that myocardial regions nurtured by the left coronary artery are more negatively affected by radiation compared to those nurtured by the right coronary artery. Conclusions: Alterations in regional tissue and strain parameters on MRI vary according to local myocardial RT dose, suggesting there may be heterogeneity of radiation sensitivity for the heart substructures and regions. Changes in segmental strain parameters may reflect post-RT cardiac remodeling, but larger confirmatory studies are required. Full article

Background: Emerging evidence suggests that antiviral treatment targeting human cytomegalovirus (HCMV) may improve outcomes in patients with glioblastoma (GBM). In this study, we analyzed serological data from the placebo-controlled VIGAS1 trial (Eudra number 2006-002022-29), which assessed the effect of valganciclovir (VGCV) on GBM progression in 42 patients, for impact of VGCV in preventing HCMV reactivation. Methods: VIGAS1 patients had undergone radical surgery and were randomized to receive either VGCV (n = 22) or placebo (n = 20) alongside standard radiochemotherapy. Blood was prospectively collected at baseline and 3-, 12- and 24-week follow-up visits. GBM cell lines and a cytomegalovirus-infected murine brain cancer model were used to validate the clinical findings. Results: Over the 24-week study period, we found that HCMV reactivation, as inferred from IgM seropositivity, occurred in 58.3% of patients in the placebo group, whereas this was completely prevented in the VGCV-treated group except for one patient with no treatment compliance (p = 0.0005). HCMV reactivation was linked to early recurrence. IgG-positive patients treated with VGCV showed a significantly longer time to progression (TTP) than those receiving placebo (6.7 vs. 3.7 months, p = 0.0408). We found a significant association between higher steroid doses and enhanced reactivation in the placebo group. In vitro and murine studies confirmed that corticosteroids, combined with radiation therapy, enhanced cytomegalovirus reactivation, which was mitigated by antiviral treatment. Conclusions: These findings suggest that preventing HCMV reactivation with antiviral therapy may improve patient outcomes, especially in HCMV-seropositive GBM patients, and further support the hypothesis that HCMV is a tumor-promoting virus. Full article

The use of proton beam therapy (PBT), as a more precision-targeted radiotherapy technique, is increasing in the treatment of head and neck squamous cell carcinoma (HNSCC). PBT benefits from the precise delivery of the radiation dose to the tumour via the Bragg peak. However, challenges still remain in the treatment of HNSCC with radiotherapy, particularly with tumour radioresistance and recurrence, requiring strategies leading to radiosensitisation. There are added complexities with the use of PBT given the increase in linear energy transfer (LET) at and around the Bragg peak, which can cause an altered cellular response compared to low-LET radiation. Nevertheless, targeting the cellular DNA damage response is considered an important strategy to enhance tumour cell killing caused by radiotherapy. Therefore, using specific inhibitors against the protein kinases ataxia telangiectasia mutated (ATM), ataxia telangiectasia and Rad3-related (ATR) and the DNA-dependent protein kinase catalytic subunit (DNA-Pkcs), we investigated their impact in radiosensitising HPV-negative HNSCC cells to PBT of increasing LET. We demonstrate that inhibitors against ATR (AZD6738), and particularly ATM (AZD1390) and DNA-Pkcs (AZD7648), could significantly decrease clonogenic survival of HNSCC cell lines following PBT at both low and relatively high LET (~2 keV/µm and ~8 keV/µm, respectively). We confirmed that the inhibitors in combination with PBT led to DSB persistence through neutral comet assays and monitoring γH2AX/53BP1 foci. We also show that this strategy can enhance the sensitivity of patient-derived organoids of HNSCC to PBT of both low and high LET, highlighting this as a strategy which should be exploited further. Full article

Background/Objectives: The selection of neoadjuvant therapy for patients with non-metastatic pancreatic adenocarcinoma remains challenging. Methods: We performed a single-institution, retrospective analysis of 79 patients who underwent resection of their pancreatic adenocarcinoma after receiving neoadjuvant therapy. Clinical and pathologic data were collected. Tumor fibrosis was quantified using Masson’s trichrome staining, tumor-infiltrating lymphocytes (TIL) were evaluated by an AI-based analysis of whole-slide H&E images, and immune cell populations were quantified by multiplex immunohistochemistry. Correlation analyses were performed between neoadjuvant treatment regimen, tumor regression, immune phenotypes, and survival. Results: All patients received chemotherapy, 77% FOLFIRINOX and 23% Gemcitabine/nab-paclitaxel (Abraxane). Eighteen percent of patients went on to receive radiation. Tumor regression grade (TRG) correlated with the neoadjuvant regimen. A reduction in tumor markers and the baseline neutrophil-to-lymphocyte ratio (NLR) correlated with overall survival. Among patients with an NLR > 3.3, FOLFIRINOX conferred a survival benefit over Gemcitabine/nab-paclitaxel, and radiation trended towards improved survival. Radiation was associated with increased fibrosis and reduced infiltration of CD8⁺ and regulatory T cells (Tregs). Increased Tregs and PDL1⁺ stromal cells were associated with poor response to neoadjuvant therapy, and NLR > 3.3 correlated with increased Treg infiltration. Conclusions: Our data suggest that patients with a high baseline NLR may benefit from intensified neoadjuvant therapy with FOLFIRINOX and radiation. Combination immunotherapy targeting Tregs and the PD1/PDL1 axis may further improve outcomes. Full article

Primary cutaneous anaplastic large cell lymphoma (pcALCL) is a type of cutaneous T-cell lymphoma (CTCL) classified as a CD30+ lymphoproliferative disorder along with lymphomatoid papulosis. Although it is the second most common subtype of CTCL after mycosis fungoides/Sézary syndrome, it remains rare, with an incidence of fewer than 0.5 cases per million person-years. Despite its histologic similarity to systemic anaplastic large cell lymphoma, pcALCL follows a largely indolent course with excellent outcomes, with disease-specific survival rates of 86–95% in contemporary series. This narrative review summarizes the clinical presentation, diagnostic evaluation, and management of pcALCL based on a semi-structured literature search, with emphasis on prospective studies and clinically relevant retrospective data. Diagnosis remains challenging due to overlap with other CD30-positive lymphoproliferative disorders and reactive conditions, requiring careful clinicopathologic correlation and exclusion of systemic disease. While regional lymph node involvement may be present, available evidence suggests it does not significantly impact prognosis, highlighting the importance of avoiding overtreatment. Management strategies are guided by disease extent, with strong evidence supporting skin-directed therapies, particularly radiation, for localized disease. For multifocal or relapsed disease, brentuximab vedotin demonstrates the most robust prospective data and has reshaped the treatment landscape; however, alternative systemic therapies, including methotrexate and retinoids, remain relevant in selected patients. Overall, current management is supported largely by non-randomized data, and key gaps remain in risk stratification, optimal sequencing of therapies, and management of uncommon aggressive variants. Full article

Background/Objectives: Primary spinal sarcomas, encompassing both bone and soft tissue histotypes, demand individualized reconstruction due to heterogeneous tumor biology, anatomic complexity, and host environments compromised by radiation, systemic therapy, or prior surgery. This narrative review reframes post-resection spinal reconstruction through a precision-medicine lens. Methods: A structured literature review was performed using PubMed and Scopus, targeting articles published between 2000 and 2026. Searches encompassed spinal sarcoma reconstruction, radiation and fusion, biologic reconstruction, and emerging technologies. Results: Tumor grade, radiation exposure, and systemic therapy timing emerge as multiplicative determinants of reconstructive environment quality, with drug-class-specific perioperative effects warranting stratified management. Vascularized bone grafts achieve reliable fusion in compromised hosts where avascular constructs fail. A precision-oriented reconstructive ladder is proposed as a conceptual, hypothesis-generating framework to guide strategy selection. Hybrid PSI-VBG constructs may further expand reconstructive possibilities. The evidence base remains largely composed of small, retrospective series. Conclusions: Individualized strategies anchored in tumor biology and host environment are the cornerstone of durable spinal sarcoma reconstructions. The proposed framework requires prospective, multi-institutional validation. Standardized outcome definitions, prospective registries, and histotype-stratified analyses are needed to advance the field. Full article

Recent studies have reported skin microbiome dysbiosis in patients with photodermatoses, featuring enriched Staphylococcus aureus colonization and decreased microbiome diversity. We propose that ultraviolet radiation (UVR), along with atypical antimicrobial peptides, may exert selective pressure on the skin microbiome, while cytokine dysregulation and a reduction in commensal bacteria amplify microbial dysbiosis. Dysbiotic microorganisms further release pathogen-associated patterns and virulence factors, and activate tissue-resident memory T cells, which collectively contribute to local inflammation. These mechanisms establish the skin microbiome as a potential target for early intervention. Potential therapeutic strategies may include antibiotics, phototherapy, bleach baths, phage therapy, and microbiota-based therapies. This review integrates current findings from microbial ecology, molecular biology, and host immunology to outline a conceptual framework linking UVR exposure, microbiome alterations, and cutaneous immune responses, while emphasizing the current limitations and evidence gaps in this field. Full article

Background: The management of localized prostate cancer (PCa) suffers from the dilemma between the overtreatment associated with radical surgery and the uncertainty of active surveillance, highlighting a significant therapeutic gap specifically for intermediate-risk patients and selected low-risk patients. Focal therapy (FT) emerges as an advanced technological solution to balance rigorous oncological control with anatomical and functional preservation. Methods: A narrative review of the literature was conducted to analyze the physical principles underlying various ablative energies (thermal, cryogenic, and non-thermal) as well as radiation-based focal approaches. The review examines the oncological rationale of targeted ablation, recent innovations in imaging, and the expanding clinical scenarios for FT application. Results: Evidence supports the oncological rationale of “Index Lesion” ablation as a targeted curative strategy for clinically significant disease, rather than merely a palliative one. The review highlights the emerging concept of “pushing the disease” and demonstrates the valuable role of salvage focal therapy in the setting of radio-recurrent carcinoma. Furthermore, recent innovations in multiparametric magnetic resonance imaging (mpMRI) and fusion systems have significantly refined patient selection, rendering this minimally invasive approach highly targeted. Conclusions: The current barrier to the universal adoption of focal therapy is the lack of a standardized consensus on the definitions of therapeutic failure and the inadequacy of traditional PSA-based criteria. However, evidence suggests that FT represents a promising, organ-sparing alternative for carefully selected patients with localized PCa, though long-term comparative data are still required. Full article