Search Results (1,354)

Photodynamic therapy (PDT) is a minimally invasive therapeutic modality based on the interaction between a photosensitizer (PS), light, and molecular oxygen to generate reactive oxygen species (ROS) capable of inducing localized cytotoxicity. Natural products provide a chemically diverse source of photosensitizers, including curcumin, hypericin, hypocrellin, chlorin derivatives, alkaloids, flavonoids, anthraquinones, and other photoactive scaffolds. However, their translational development remains limited by poor solubility, aggregation, instability, variable purity, limited tissue penetration, suboptimal pharmacokinetics, and insufficient formulation readiness. In parallel, artificial intelligence (AI), including machine learning (ML), deep learning (DL), quantitative structure–activity relationship (QSAR) and quantitative structure–property relationship (QSPR) modeling, radiomics, and predictive analytics, is increasingly being applied to photosensitizer discovery, molecular property prediction, nanoformulation optimization, treatment planning, and precision PDT. This critical review evaluates the intersection between AI, natural photosensitizers, nanopharmaceutical development, and PDT, with emphasis on methodological strengths, current limitations, and translational priorities. A PRISMA 2020-inspired search strategy identified 27 studies for qualitative synthesis, comprising 11 review articles and 16 original investigations, while additional seminal references were used for historical and mechanistic contextualization. The analysis indicates that current AI applications in PDT are concentrated around molecular property prediction, QSAR/QSPR modeling, phototoxicity assessment, radiomics, image-guided therapy, and treatment-response prediction, whereas AI-guided exploration of natural photosensitizer chemical space and AI-assisted nanoformulation design remain comparatively underdeveloped. Key barriers include heterogeneous datasets, limited natural-product representation in predictive models, insufficient external validation, weak integration between formulation variables and photodynamic outcomes, and limited consideration of manufacturing and regulatory requirements. This review proposes an integrated AI-enabled translational framework connecting natural-product chemical diversity, photochemical prediction, nanocarrier optimization, precision PDT validation, and clinical implementation. Full article

Dental caries is one of the most prevalent chronic diseases affecting older adults and remains an important, underrecognized contributor to pain, impaired nutrition, systemic illness, and reduced quality of life. Older adults access medical care more often than dental care, positioning non-dental clinicians to identify risk, initiate prevention, and facilitate timely referral. A narrative review of English-language literature was conducted using PubMed and Google Scholar. Search terms included “dental caries,” “root caries,” and “older adults.” Sources included original studies, clinical guidelines, consensus statements, and high-quality reviews, with an emphasis on relevance to older adults and applicability to non-dental clinicians. Dental caries in older adults commonly presents as root and recurrent decay and isstrongly associated with xerostomia, polypharmacy, chronic disease, functional impairment, cognitive decline, and limited access to dental care. The literature supports fluoride-based prevention, management of salivary dysfunction, dietary counseling, minimally invasive therapies such as silver diamine fluoride, and interprofessional care models. Non-dental providers play a critical role in screening, risk assessment, preventive counseling, symptom triage, and referral. Integrating oral health into routine medical care is an essential and achievable strategy to reduce morbidity and improve health outcomes in older adults. Full article

Cholangiocarcinoma (CCA) is an aggressive malignancy associated with malignant biliary obstruction and it has poor overall survival. Most patients present with unresectable disease which limits curative treatment options and highlights the need for effective palliative therapies. Endobiliary radiofrequency ablation (RFA) has emerged as a minimally invasive technique aimed at reducing intraductal tumor burden, improving biliary drainage, and potentially prolonging survival. Recently, multiple randomized controlled trials, retrospective studies, and meta-analyses have evaluated the role of endobiliary RFA in patients with CCA, with mixed results. Available evidence suggests that RFA may provide a survival benefit in selected patients. However, its effects on stent patency and quality of life remain inconsistent across studies. Current data also demonstrate an overall acceptable safety profile. In this review, we summarize the procedural techniques, currently available evidence, adverse events, patient selection considerations, guideline recommendations, and future directions regarding the use of endobiliary RFA in CCA. Full article

Circulating tumor DNA (ctDNA) has emerged as a promising minimally invasive biomarker in multiple myeloma (MM), providing dynamic insight into tumor burden, clonal evolution and molecular heterogeneity. Unlike conventional bone marrow-based diagnostics, ctDNA analysis offers a systemic approach to disease assessment and may better reflect spatially heterogeneous and extramedullary disease. Recent advances in highly sensitive molecular techniques, including digital droplet polymerase chain reaction and next-generation sequencing, have improved the feasibility of ctDNA detection and longitudinal disease monitoring in MM. Increasing evidence demonstrates substantial concordance between ctDNA and bone marrow genomic profiles, while also highlighting the ability of ctDNA to identify resistant subclones, molecular relapse and genomic evolution during therapy. ctDNA has shown potential clinical utility in molecular profiling, therapeutic monitoring and minimal residual disease assessment. ctDNA may become increasingly relevant in the era of novel immunotherapies, including chimeric antigen receptor T-cell therapy and bispecific antibodies. Despite these promising applications, several biological and technical limitations still restrict routine clinical implementation, including low ctDNA concentration in patients with minimal disease burden and lack of methodological standardization. Overall, ctDNA represents a rapidly evolving tool with significant potential to improve personalized disease monitoring and therapeutic strategies in MM. Full article

Background/Objectives: Orthodontic mini-implants have become an essential source of temporary skeletal anchorage because of their versatility, minimal invasiveness, and reduced dependence on patient compliance. However, their clinical success relies on maintaining adequate primary and secondary stability throughout orthodontic treatment. Photobiomodulation (PBM) with diode lasers has been proposed as a non-invasive adjunctive therapy capable of enhancing bone healing and remodeling, thereby improving mini-implant stability. Despite encouraging findings, the available evidence remains limited and heterogeneous. The objective was to systematically evaluate the effect of diode laser photobiomodulation on the stability of orthodontic mini-implants. Methods: A systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The search was conducted in the PubMed, EBSCO, Scopus, and ScienceDirect databases to identify randomized clinical trials published in the last 10 years. Five randomized controlled trials involving 89 participants and 178 orthodontic mini-implants fulfilled the eligibility criteria. Mini-implant stability was assessed using objective methods, including resonance frequency analysis (ISQ) and Periotest values, while one study also evaluated insertion and removal torque. The methodological quality of the included studies was assessed using the Cochrane Risk of Bias 2 (RoB 2) tool, and the certainty of the evidence was evaluated using the GRADE approach. Results: Three of the five included studies reported improvements in orthodontic mini-implant stability following diode laser photobiomodulation, whereas two studies found no significant differences compared with the control group. Considerable heterogeneity was identified regarding laser wavelength (618–940 nm), irradiation protocols, energy parameters, timing of force application, and stability assessment methods. Most studies presented a low risk of bias, although some concerns remained regarding allocation concealment and blinding. According to the GRADE assessment, the overall certainty of the evidence was considered moderate, mainly because of inconsistency across studies and methodological heterogeneity. Conclusions: Current evidence suggests that diode laser photobiomodulation may improve the stability of orthodontic mini-implants. Nevertheless, the small number of randomized clinical trials and the substantial variability in PBM protocols and outcome assessment methods preclude definitive clinical recommendations. Future well-designed randomized controlled trials using standardized irradiation parameters and uniform stability assessment methods are required to establish evidence-based clinical protocols. Full article

Background and Objectives: Endoscopic ultrasound-guided radiofrequency ablation (EUS-RFA) is an emerging minimally invasive therapeutic option for pancreatic and selected extra-pancreatic lesions. However, its clinical adoption is limited by heterogeneous indications, non-standardized techniques, and variable quality of evidence. This systematic review assessed the published literature on EUS-RFA and classified available evidence according to the Oxford Centre for Evidence-Based Medicine levels of evidence. Materials and Methods: A systematic search was performed to identify peer-reviewed studies reporting clinical or translational data on EUS-RFA. Studies were grouped by indication, including pancreatic insulinoma, non-functioning pancreatic neuroendocrine neoplasms, branch-duct intraductal papillary mucinous neoplasms and other pancreatic cystic neoplasms, pancreatic ductal adenocarcinoma, pancreatic metastases, adrenal adenoma, and miscellaneous indications. Each study was categorized according to Oxford level of evidence based on study design. Results: Thirty-seven records were included in the final evidence map, comprising 36 clinical studies classifiable according to Oxford levels of evidence and one translational record not classifiable as clinical therapeutic evidence. Among the 36 clinically classifiable studies, one provided Level 1b evidence, consisting of a randomized trial evaluating EUS-guided celiac ganglion RFA for pancreatic cancer-related pain palliation, and three provided Level 2b evidence, including non-randomized comparative cohorts in pancreatic insulinoma and unresectable pancreatic ductal adenocarcinoma. Most clinically classifiable studies were Level 4 evidence (32/36), mainly uncontrolled prospective or retrospective cohorts and case series. One preclinical/translational study was not classifiable within clinical therapeutic evidence levels. Pancreatic insulinoma was the most evidence-supported tumor-ablation indication, with comparative data suggesting efficacy comparable to surgery and a more favorable safety profile. For non-functioning pancreatic neuroendocrine neoplasms, branch-duct IPMN, renal cell carcinoma pancreatic metastases, and adrenal adenomas, available data suggest feasibility and encouraging short-term outcomes but remain predominantly non-comparative. In pancreatic ductal adenocarcinoma, EUS-RFA remains investigational as an adjunct to systemic therapy. Conclusions: EUS-RFA is a promising therapeutic platform, but evidence remains highly indication-dependent and dominated by low-level observational studies. Standardized protocols, indication-specific outcomes, prospective registries, and comparative trials are needed. Full article

Background/Objectives: Recurrent temporomandibular joint dislocation is associated with repeated dislocation episodes, pain, impaired jaw function, and psychosocial burden. Injectable intra- and periarticular therapies have been proposed as minimally invasive methods of improving joint stability, but the available evidence is heterogeneous and frequently involves adjunctive procedures. This mapping review aimed to characterize injectable treatments whose effects could be assessed independently from simultaneous non-injectable interventions. Methods: PubMed (MEDLINE), Europe PMC, and BASE were searched from inception to 7 April 2026. Reference lists of included studies and relevant reviews were also screened. Studies reporting clinical outcomes of injectable intra- or periarticular treatments for recurrent mandibular dislocation were eligible when the effect of the injectable component could be evaluated independently. Study selection, data charting, and critical appraisal were performed using predefined methods. Results: Five primary clinical studies and eight secondary mapping or reference-checking sources were included. The primary studies evaluated autologous blood injection, dextrose prolotherapy, and sodium morrhuate or other sclerosing-agent injections. Most studies reported reductions in recurrent dislocation or subluxation and improvements in joint stability. Some also reported improvements in maximal mouth opening, clicking, pain, or other clinical outcomes. However, the evidence was limited by small sample sizes, heterogeneous protocols, variable injection sites, and limited comparative data. Conclusions: The available literature on injectable therapies for recurrent mandibular dislocation is limited and heterogeneous. Although included studies generally reported favorable outcomes, the evidence does not permit conclusions regarding the comparative effectiveness or superiority of any specific injectable modality. Full article

The left atrial appendage is well recognized as the site of thrombus formation in patients with atrial fibrillation. However, in patients who are either unsuitable for long-term oral anticoagulation or in whom this therapy is inefficient, left atrial occlusion has emerged as a mechanical strategy option to diminish stroke risk. Minimally invasive percutaneous and standalone surgical thoracoscopic techniques are appearing as viable options for left atrial appendage exclusion, each with distinct procedural risk profiles and characteristics, as well as evidence from trials or registers. We suggest that the choice between percutaneous and thoracoscopic left atrial appendage occlusion should be individualized, ideally within the multidisciplinary heart team, considering left atrial appendage anatomy, patient bleeding and thromboembolic risk profile, comorbidities, prior cardiac interventions, and institutional expertise and resources. We aim to present in this review the value of multimodality imaging in patient selection for minimally invasive left atrial appendage occlusion to minimize the possibility of complications, and to compare technical advancements and indications for percutaneous and standalone thoracoscopic left atrial appendage occlusion. Full article

Glioblastoma (GBM) is the most common and aggressive primary brain tumor, characterized by poor prognosis and a median survival of 12–18 months despite standard therapies such as surgery, radiation, and temozolomide chemotherapy. Its high cellular heterogeneity, along with complex mechanisms of therapy resistance, presents significant challenges for effective treatment. Conventional systemic chemotherapy is limited by the blood–brain barrier (BBB), systemic toxicity, and insufficient drug penetration into the tumor microenvironment. Emerging therapeutic strategies aim to overcome these barriers through novel chemotherapeutic agents, targeted therapies, immunotherapies, and smart drug delivery systems. Endovascular drug delivery, particularly super-selective intra-arterial cerebral infusion (SSIACI), offers a minimally invasive approach to directly target the tumor vasculature, potentially increasing drug concentration at the tumor site while reducing systemic exposure. Complementary techniques, such as MR-guided focused ultrasound, hyperosmotic disruption, and nanoparticle-based carriers, are being explored to enhance BBB penetration and retention of therapeutics within the tumor. Ongoing clinical trials and translational studies provide insights into optimizing these approaches, with future directions focused on precision medicine, biomarker-driven patient selection, and combination therapies. Integrating endovascular strategies with innovative chemotherapies and immunotherapies may transform GBM management, but further research is required to establish their efficacy and safety in clinical practice. Full article

Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of aggressive non-Hodgkin lymphoma and is characterized by pronounced molecular heterogeneity that is not always fully captured by standard histopathological assessment. Circulating tumor DNA (ctDNA) is increasingly regarded as a promising liquid-biopsy biomarker that enables non-invasive molecular tumor profiling, assessment of tumor burden, dynamic monitoring of treatment response, and detection of measurable/minimal residual disease (MRD). Modern analytical platforms, ranging from PCR-based assays to next-generation sequencing approaches, including CAPP-Seq and PhasED-Seq, have substantially expanded the possibilities of molecular monitoring in DLBCL. This review summarizes current data on the biological characteristics of ctDNA, contemporary methods for its analysis, concordance between ctDNA and tumor-tissue mutational profiles, and the clinical significance of baseline ctDNA levels, early molecular response, post-treatment MRD status, and molecular surveillance during remission. Special attention is given to ctDNA monitoring in patients receiving novel immunotherapies, including CAR-T cell therapy, bispecific antibodies, and antibody–drug conjugates. Emerging multi-omic approaches integrating genomic, epigenomic, and fragmentomic data are discussed as promising future directions. Key limitations of clinical implementation include insufficient standardization of preanalytical and analytical workflows, the confounding effect of clonal hematopoiesis of indeterminate potential, variability across technological platforms, and the lack of completed prospective randomized interventional studies demonstrating improved outcomes when therapy is modified according to ctDNA status. Overall, ctDNA is currently a highly informative prognostic biomarker in DLBCL; however, its full implementation as a predictive tool for treatment selection requires further harmonization, prospective validation, and confirmation in interventional clinical trials. Full article

Background/Objectives: Schlemm canal-based minimally invasive glaucoma surgery (MIGS) can be combined with cataract surgery, but topical glaucoma therapy alone is not a sufficient indication for adding MIGS. This review addresses when cataract surgery alone may be sufficient, when combined cataract surgery and MIGS may be appropriate, and when filtration surgery should be considered. Methods: This narrative review used a targeted PubMed/MEDLINE search of English-language literature published from January 2000 to May 2026 to support source identification and reference selection. The review focused on cataract surgery combined with Schlemm canal- or trabecular meshwork-targeted MIGS, including stent-based Schlemm canal procedures and trabeculotomy/goniotomy-based procedures, medication burden, ocular surface disease, refractive and visual outcomes, corneal endothelial safety, complications, angle visibility, guideline-based decision-making, and patient selection. Final references were selected according to clinical relevance to cataract-surgeon decision-making and evidence priority, with emphasis on guidelines, systematic reviews or meta-analyses, randomized or prospective comparative studies, pivotal or long-term studies, large real-world or post-market studies, and clinically informative safety, refractive, endothelial, imaging, or complication-related studies. Results: Stent-based Schlemm canal procedures and trabeculotomy/goniotomy-based procedures can provide additional IOP and medication reduction compared with cataract surgery alone in selected eyes with mild-to-moderate open-angle glaucoma. Stent-based procedures generally have a lower hyphema risk, whereas trabeculotomy/goniotomy-based procedures may provide comparable or greater IOP reduction in selected eyes but are associated with more frequent hyphema. In normal-tension glaucoma or low-baseline-IOP eyes, the expected benefit is often medication reduction or modest IOP lowering rather than reliable achievement of very low target IOP. Available refractive evidence remains limited and procedure-specific, but suggests that major refractive instability is uncommon in appropriately selected eyes. Conclusions: The decision to combine Schlemm canal-based MIGS with cataract surgery should be goal-directed rather than based solely on the presence of topical therapy. Practical selection should integrate glaucoma subtype, disease stage, baseline and target IOP, expected phacoemulsification-only IOP reduction, medication burden, ocular surface status, adherence, angle visibility, endothelial reserve, refractive objectives, and future filtration surgery options. Full article

Background/Objectives: Thoracoscopic esophagectomy is an accepted minimally invasive approach for resectable esophageal and esophagogastric junction cancer in Japan. Whether robot-assisted minimally invasive esophagectomy (RAMIE) improves short- and long-term outcomes compared with video-assisted thoracoscopic esophagectomy (VATS) remains clinically relevant. Methods: We retrospectively reviewed patients who underwent VATS or RAMIE between January 2017 and April 2026. Patients who underwent open esophagectomy, non-gastric conduit reconstruction, or staged operation were excluded. Propensity score matching (PSM) was performed using age, sex, body mass index, histology, tumor location, clinical stage, preoperative therapy, extent of lymph node dissection, abdominal approach, and reconstruction route. Long-term outcomes were explored in a PSM cohort limited to patients treated between January 2017 and December 2023. Results: The main cohort included 369 patients (VATS, n = 186; RAMIE, n = 183). Overall complications of Clavien–Dindo (CD) grade ≥ II were comparable between VATS and RAMIE (32.8% vs. 32.8%, p = 0.999), whereas RLNP CD ≥ I (9.7% vs. 3.8%, p = 0.025) and RLNP CD ≥ II (3.8% vs. 0.5%, p = 0.034) were less frequent after RAMIE. PSM yielded 128 matched pairs; RLNP remained less frequent after RAMIE (CD ≥ I, 10.9% vs. 3.1%, p = 0.015; CD ≥ II, 4.7% vs. 0%, p = 0.013), while other short-term outcomes were comparable. In the survival PSM cohort (79 pairs), 3-year overall survival (66.0% vs. 73.4%, p = 0.203) and recurrence-free survival (62.3% vs. 59.3%, p = 0.651) did not differ significantly between VATS and RAMIE. Conclusions: RAMIE showed comparable short-term safety to VATS and was associated with lower RLNP after adjustment for clinicopathological, treatment-related, and surgical factors. Exploratory long-term analysis was limited by cohort size and follow-up duration but suggested that RAMIE did not compromise oncologic outcomes. Full article

Postoperative pleural effusion (PE) is a common finding after endoscopic-assisted, minimally invasive coronary bypass surgery (Endo-CAB). This study evaluated its postoperative course, defined a threshold for clinically significant PE, and identified associated risk factors. Between May 2021 and January 2026, 727 patients were retrospectively analyzed. A total of 3141 postoperative chest X-rays obtained during hospitalization and follow-up were reviewed to quantify PE. Clinically significant PE was defined as ≥25% on radiographic assessment. Baseline characteristics and postoperative outcomes were analyzed, and logistic regression was used to identify independent risk factors. All patients received oral diuretics for two weeks after discharge as standard protocol. PE occurred in 86.1% of patients, typically developing within the first two postoperative days, with a median maximum of 13% [5–21%]. By the third postoperative week, PE had resolved to 0% [0–0%] in most cases. Adjustment of diuretic therapy was required in 18.3%, while 5.1% underwent thoracocentesis. Clinically significant PE occurred in 15.4% and was associated with longer hospital stay and increased blood transfusion rates. Independent risk factors included age, body mass index, continuation of dual antiplatelet therapy, and blood transfusion. Overall, PE is frequent but usually self-limiting after Endo-CAB. Full article

Background: Gastric and gastroesophageal junction adenocarcinomas remain major causes of cancer- related mortality worldwide. Although perioperative chemotherapy, HER2-directed therapy, Claudin-18.2 (CLDN18.2)-targeted treatment, immune checkpoint inhibition, and anti-angiogenic therapy have improved outcomes in selected patients, clinically actionable targets are absent, heterogeneous, or lost in many high-grade, diffuse, poorly cohesive, signet-ring-cell micropapillary, hepatoid, and sarcomatoid carcinomas. Additional histopathology-assessable biomarkers that can support both molecular imaging and targeted therapy are of considerable clinical interest. Methods: Integrin αvβ6 is an epithelial-specific adhesion receptor that is minimally expressed in most normal adult tissues but becomes markedly upregulated during epithelial carcinogenesis, tissue remodeling, invasion, and activation of transforming growth factor-β signaling. This retrospective histopathological and immunohistochemical study evaluated integrin αvβ6 expression by immunohistochemistry in 53 formalin-fixed paraffin-embedded diagnostic specimens of untreated primary gastric or gastroesophageal junction adenocarcinoma. Tumors were classified according to the WHO Classification of Tumors of the Digestive System, 5th edition. Membranous integrin αvβ6 staining intensity and the percentage of positive tumor cells were recorded, and an H-score was calculated. Expression patterns were compared descriptively with histological subtype, differentiation grade, HER2 status, and CLDN18.2 expression. Results: Integrin αvβ6 immunoreactivity was detected in 49 of 53 tumors (92.5%), the clinically more relevant moderate to strong expression (H-score > 100) was present in 27 of 53 cases (50.9%), and strong expression was present in 13 of 53 cases (24.5%). Expression was not confined to conventional intestinal-type tumors; among carcinomas containing a signet-ring-cell component, 14 of 16 assessable cases (87.5%) showed integrin αvβ6 positivity, with 8 of 16 (50.0%) showing moderate to strong staining. By comparison, HER2 positivity was identified in 4 of 53 cases (7.5%; 4 of 52 assessable cases, 7.7%), and clinically relevant CLDN18.2 positivity, defined as moderate-to-strong membranous staining in at least 75% of tumor cells, was present in 7 of 38 assessable cases (18.4%). Conclusions: Integrin αvβ6 is frequently expressed in gastric and gastroesophageal junction adenocarcinoma, with moderate to strong expression in approximately half of all cases and in half of signet ring cell-containing tumors, including aggressive histological subtypes that often lack established therapeutic targets. The precise H-Score threshold for theranostic eligibility remains to be determined. The findings support integrin αvβ6 as a promising biomarker for histopathology-based screening, PET-based whole-body target assessment, and future targeted radionuclide therapy. Integration of immunohistochemistry and integrin αvβ6- targeted PET imaging will be essential to validate integrin αvβ6 as a candidate biomarker and to optimize radionuclide selection in gastric cancer, particularly with moderate to strong expression. Full article

Postoperative complications following colorectal surgery—including anastomotic leak (AL), surgical site infection (SSI), perioperative haemorrhage and colovesical fistula—represent major causes of patient morbidity and mortality, prolonged hospitalisation, and healthcare expenditure. This review summarises contemporary evidence across two key domains of complication management—prevention and diagnosis—applied to four major complications (AL, SSI, perioperative haemorrhage, and colovesical fistula), drawn from a comprehensive literature review of recent randomised controlled trials, systematic reviews, meta-analyses, and prospective cohort studies. Preventive strategies discussed include optimisation of surgical techniques (minimally invasive and robotic approaches, indocyanine green perfusion assessment, self-expanding metal stent bridge-to-surgery, and negative pressure wound therapy), modification of patient factors where possible (obesity, anaemia, malnutrition, and immunosuppression), and system-level interventions including Enhanced Recovery After Surgery (ERAS) protocols, perioperative beta-blockade, prehabilitation, and structured quality improvement bundles. Diagnostic strategies have evolved to incorporate biomarker surveillance (CRP and procalcitonin), drain fluid pH analysis, CT imaging (including angiography), endoscopy, and novel digital health tools including wearable monitoring and mobile health applications. Reducing the risk of postoperative complications should involve a multidisciplinary, protocolised approach combining intraoperative technique optimisation with structured perioperative care bundles and close post-discharge surveillance, and centralisation to specialist colorectal surgical units. Full article