Search Results (7,537)

Traditional Mediterranean grapevine landraces represent irreplaceable reservoirs of adaptive diversity, yet many regional germplasm pools remain poorly characterized, limiting conservation strategies and climate-resilient breeding. This study presents the first comparative genetic assessment of 154 local Vitis accessions from three historically interconnected but genomically underrepresented Mediterranean regions: Greece, Morocco, and Slovenia. Using 12 highly polymorphic nuclear SSR markers, we detected substantial genetic diversity (168 alleles; mean heterozygosity He = 0.881) with distinct regional signatures. Moroccan accessions exhibited the highest allelic richness and 11 private alleles, reflecting diverse agroecological adaptation. Slovenian germplasm formed a cohesive, genetically stable cluster with high effective allele numbers. Greek accessions exhibited the highest observed heterozygosity and 14 private alleles, consistent with the Aegean’s role as a major diversification hotspot. Despite >90% of variance occurring within individuals, AMOVA and pairwise FST (0.050–0.061) revealed low to moderate but significant geographic differentiation. Multivariate analyses (PCA, UPGMA) and Bayesian clustering (sNMF, K = 3) consistently resolved three regional genetic groups with varying admixture levels, consistent with a mosaic domestication model, as previously proposed for the Mediterranean basin, shaped by recurrent introductions, wild introgression, and region-specific selection. Our results show that peripheral Mediterranean germplasm harbors meaningful, regionally distinctive, substantial, non-redundant diversity not fully represented in surveys focused on climate adaptation, disease resistance breeding, and long-term genetic resource conservation. These findings challenge simplistic diffusion models and emphasize the strategic importance of geographically comprehensive sampling in grapevine conservation programs. Full article

Background/Objectives: Non-small cell lung cancer (NSCLC) remains associated with high mortality, frequent late-stage diagnosis, biological heterogeneity, and recurrence after treatment. Although molecular and immunohistochemical biomarkers have transformed treatment selection, there remains a need for accessible, repeatable, and clinically practical circulating biomarkers that may support prognosis and post-treatment monitoring. This review discusses prolactin (PRL) as a candidate supplementary biomarker in NSCLC, with particular emphasis on its biological rationale, potential prognostic relevance, and possible role in personalized risk stratification after systemic therapy. Methods: This narrative review summarizes current evidence on established biomarkers in NSCLC, the physiology and regulation of PRL, PRL/PRLR signaling in cancer biology, mechanisms of PRL dysregulation in lung cancer, and available clinical observations concerning PRL alterations in NSCLC. Particular attention is given to the distinction between prognostic and predictive biomarkers, longitudinal monitoring, pituitary involvement, immune checkpoint inhibitor-related endocrine effects, and biological, pharmacological, and analytical confounders affecting PRL interpretation. Results: Current evidence suggests that PRL may be biologically relevant in NSCLC through its involvement in pathways related to cell proliferation, survival, angiogenesis, invasion, epithelial–mesenchymal transition, immune modulation, and possible therapy resistance. Clinical observations indicate that altered PRL levels may occur in advanced disease, pituitary involvement, systemic inflammation, stress, or during anticancer and supportive treatment. However, PRL lacks cancer specificity and is influenced by multiple confounders, including circadian rhythm, stress, endocrine disorders, macroprolactin, cachexia, medications, and assay variability. Available clinical data remain limited and are largely derived from small studies or case-based evidence. Conclusions: PRL should not currently be considered a standalone diagnostic, predictive, or treatment-selective biomarker in NSCLC. Its most realistic potential role is as a supplementary circulating marker within multimarker prognostic and monitoring models. Prospective validation with standardized sampling, assay procedures, and confounder adjustment is required before clinical implementation. Full article

Background and Objectives: To evaluate the concordance and relative performance of the 2023 American College of Rheumatology (ACR)/European Alliance of Associations for Rheumatology (EULAR) classification criteria compared with the revised Sapporo (2006) criteria and to identify potential risk factors for recurrent thrombosis among patients classified as antiphospholipid syndrome (APS) according to the 2023 criteria. Materials and Methods: This retrospective cohort study included 82 patients with documented antiphospholipid antibody (aPL) positivity between October 2022 and August 2024. The revised Sapporo criteria were used as the comparator classification system to evaluate the concordance and relative performance of the 2023 ACR/EULAR criteria. Secondary analyses were restricted to patients fulfilling the 2023 criteria (n = 55), in whom clinical characteristics and potential risk factors for recurrent thrombosis were evaluated. Results: Of the 82 aPL-positive patients, 9 fulfilled only the revised Sapporo criteria, 1 fulfilled only the 2023 criteria, 54 met both criteria sets, and 18 met neither. Using the revised Sapporo criteria as the comparator, the 2023 criteria demonstrated a relative sensitivity of 85.7% and relative specificity of 95.0%. Positive and negative agreement rates were 98.2% and 66.7%, respectively. Among patients classified as APS according to the 2023 criteria, disease duration was significantly longer in patients with recurrent thrombosis in univariate analysis (p = 0.028); however, this association did not remain significant after multivariable adjustment. Conclusions: The 2023 ACR/EULAR criteria demonstrated higher relative specificity but lower relative sensitivity compared with the revised Sapporo criteria. No independent predictor of recurrent thrombosis was identified after multivariable adjustment, although the limited number of outcome events may have reduced statistical power. However, most recurrent thrombotic events occurred in patients with subtherapeutic INR levels, suggesting the importance of careful anticoagulation management in patients with APS. Full article

Objective: Pediatric intestinal pseudo-obstruction (PIPO) is a rare, severe, and heterogeneous gastrointestinal motility disorder associated with intestinal failure, recurrent hospitalizations, and significant morbidity and mortality. This study aimed to evaluate the clinical features, management strategies, and long-term outcomes of children diagnosed with PIPO at a tertiary referral center. Methods: This retrospective single-center study included pediatric patients diagnosed with PIPO between 2011 and 2025. Diagnosis was established according to ESPGHAN consensus criteria. Demographic characteristics, clinical presentation, genetic findings, nutritional support, surgical interventions, intestinal transplantation, and long-term outcomes were retrospectively reviewed. Results: A total of 32 patients with PIPO were included, of whom 56.2% were female and 43.7% had early-onset disease. Genetic testing was performed in 22 of 32 patients; clinically significant variants were identified in 16 (50% of the total cohort), most commonly ACTG2 mutations. Prior abdominal surgery before referral was present in 84.3% of patients. During follow-up, 56% remained parenteral nutrition dependent, five patients underwent intestinal transplantation, and the overall mortality rate was 21.8%. Conclusions: PIPO is a highly heterogeneous disorder associated with substantial morbidity, prolonged nutritional support requirements, repeated surgical interventions, and significant mortality. Early diagnosis, genetic evaluation, multidisciplinary management, and timely referral to specialized intestinal failure and transplantation centres are likely to support more individualised management and may help prevent avoidable complications in affected children. Full article

Membranous nephropathy (MN) and minimal change disease (MCD) are the most common causes of nephrotic syndrome following hematopoietic stem cell transplantation (HSCT), a complication conventionally attributed to chronic graft-versus-host disease (GVHD). Paraneoplastic MCD is well described in lymphoid malignancies but is rarely reported in myeloid neoplasms. We report two cases of biopsy-confirmed MCD presenting as the initial manifestation of acute myeloid leukemia (AML) relapse following allogeneic HSCT. Both patients were White men in their sixties with relapsed/refractory AML who developed nephrotic-range proteinuria and acute kidney injury after matched unrelated donor HSCT without histologic evidence of GVHD. Renal biopsies confirmed MCD in both cases. Corticosteroid therapy was ineffective in halting renal deterioration; renal function improved only after initiation of leukemia-directed therapy, with one patient achieving dialysis independence. These cases highlight a rare paraneoplastic presentation of AML relapse. Nephrotic syndrome due to MCD may signal post-HSCT leukemia recurrence, and evaluation for AML relapse warrants consideration in steroid-refractory cases or those without concurrent GVHD. In such cases, control of the underlying malignancy, rather than escalation of immunosuppression, may be central to renal recovery. Full article

Purpose/Objective: To evaluate the safety and failure patterns of consolidative hypofractionated thoracic radiotherapy (RT) following induction chemoimmunotherapy in patients with unresectable locally advanced non-small cell lung cancer (LA-NSCLC). Materials/Methods: This retrospective study included 34 patients treated between 2019 and 2025. All patients received induction chemoimmunotherapy followed by consolidative hypofractionated RT based on multidisciplinary tumor board recommendations. The primary endpoint was local recurrence (LR); secondary endpoints were regional recurrence (RR), distant metastasis (DM), overall survival (OS), progression-free survival (PFS), and treatment-related toxicity. Results: Median age was 64 years, and median PD-L1 expression was 20%. Most patients had stage III disease; squamous cell carcinoma (56%) and adenocarcinoma (38%) were the predominant histologies. The most common systemic regimen was carboplatin/paclitaxel plus nivolumab, with a median of four induction cycles. Post-induction response was complete in 21%, partial in 62%, stable in 12%, and progressive in 6%. Median RT dose was 52.5 Gy in 15 fractions, and maintenance immunotherapy was administered in 79%. At a median follow-up of 16.7 months, using cumulative incidence functions with death treated as a competing event, the 1- and 2-year cumulative incidences of local failure were 6.9% and 14.7%, respectively. The corresponding cumulative incidences of regional failure were 10.2% and 18.8%, while distant metastasis incidences were 15.9% and 39.2%. No isolated local or regional recurrences occurred. One- and two-year OS rates were 86% and 81%, and corresponding PFS rates were 76% and 54%. No grade 4–5 RT-related toxicity occurred; one grade 5 immune-related pneumonitis was observed. Conclusions: Consolidative hypofractionated RT following chemoimmunotherapy appears feasible and associated with favorable outcomes, supporting further prospective investigation. Full article

Background: High-grade endometrial stromal sarcoma (HGESS) is a rare and aggressive uterine mesenchymal tumor with a significant potential for recurrence and metastasis. Advances in molecular pathology have identified recurrent gene fusions involving the neurotrophic tyrosine receptor kinase (NTRK) genes, which are crucial for tumorigenesis. The identification of NTRK fusions has significant therapeutic implications, as targeted therapies such as Larotrectinib, a selective tyrosine receptor kinase (TRK) inhibitor, have demonstrated remarkable efficacy in NTRK fusion-positive tumors across various tumor histologies. Case Presentation: This report depicts the case of a 42-year-old woman with HGESS harboring an NTRK fusion diagnosed by histopathology and immunohistochemistry after undergoing a vaginal myomectomy. She subsequently underwent a robotic total hysterectomy, bilateral salpingo-oophorectomy, and bilateral lymph node dissection. Following a four-year disease-free interval, HGESS relapsed. The patient received three cycles of gemcitabine plus docetaxel. Subsequent CT imaging indicated progression of the pelvic mass. Molecular testing identified an NTRK fusion. Accordingly, larotrectinib was initiated in the setting of progressive disease. After three months, imaging demonstrated a significant decrease in the pelvic mass and near-complete radiographic resolution of the pulmonary nodules. The patient remained on larotrectinib, with January 2024 imaging showing no evidence of recurrence. Conclusions: The case presented highlights a personalized approach based on molecular profiling, and the successful use of larotrectinib, a TRK inhibitor, after the identification of an NTRK fusion-positive HGESS, emphasizing the importance of molecular diagnostics and targeted therapy in managing this rare malignancy. Full article

Renal cell carcinoma (RCC) is a biologically heterogeneous malignancy characterized by variable clinical behavior and diverse molecular phenotypes. Although immune checkpoint inhibitors and targeted therapies have transformed the treatment landscape of advanced RCC, clinically validated biomarkers capable of improving risk stratification, therapeutic-decision making and disease monitoring remain lacking. Kidney injury molecule-1 (KIM-1), also known as hepatitis A virus cellular receptor-1 (HAVCR1) or T-cell immunoglobulin and mucin domain-containing protein-1 (TIM-1), has emerged as a biologically compelling investigational biomarker e because of its close relationship to proximal tubular epithelial injury and renal carcinogenesis. KIM-1 is a transmembrane glycoprotein minimally expressed in normal kidney tissue but markedly upregulated in dedifferentiated proximal tubular epithelial cells following injury, and in clear cell RCC, where its extracellular domain can be shed into plasma and urine. Beyond its role as a marker of tubular injury, KIM-1 participates in immune regulation, phagocytosis, inflammatory signaling and tissue remodeling, supporting its potential relevance to tumor biology. Clinical studies have demonstrated associations between elevated circulating KIM-1 levels and RCC diagnosis, recurrence risk, and survival outcomes, particularly in localized and postoperative disease settings. KIM-1 has additionally been investigated as a therapeutic target through antibody–drug conjugate approaches. Despite promising translational data, important limitations yet remain. Current evidence is predominantly prognostic rather than predictive, and substantial analytical and biological challenges continue to limit implementation. Assay standardization, clinically meaningful cutoffs, specimen selection, timing of sampling, and confounding by chronic kidney disease or nonmalignant renal injury remain incompletely resolved. Furthermore, evidence supporting incremental value beyond established clinicopathologic models remains limited. This review critically evaluates the biological rationale, analytical considerations and clinical evidence supporting KIM-1 in RCC. Particular emphasis is placed on distinguishing prognostic, predictive, pharmacodynamic, and therapeutic applications, as well as defining the evidentiary gaps that must be addressed before clinical implementation. Current evidence is derived predominantly from retrospective and exploratory analyses, and important limitations remain regarding assay standardization, biological specificity, chronic kidney disease-related confounding, and prospective validation. The review concludes with a summary of the evolving landscape of KIM-1-directed biomarker strategies in RCC, which may ultimately contribute to improved biologic risk stratification and biomarker-driven clinical investigation in RCC. Full article

Ultraviolet (UV) light exposure is a recognised risk factor for dermal haemangiosarcoma (HSA) in dogs and dermal squamous cell carcinoma (SCC) in dogs and cats. These tumours cause substantial local disease and often require repeated surgery due to recurrence or de novo lesions, creating a notable welfare and financial burden. Research on preventing harmful UV exposure in pets is still in its infancy, particularly in relation to the safety of UV filters used in sunscreens. This review summarises the current evidence on UV-induced carcinogenesis, strategies to reduce UV exposure, and the safety of sunscreen ingredients in dogs and cats. UV light is strongly implicated in a range of dermatoses, from actinic keratosis to dermal HSA and SCC in dogs and cats, and the risk is likely higher in Australian pets. Indoor confinement during peak UV periods, shade, and sun-protective clothing can reduce exposure, with sunscreen an additional strategy. Sunscreen is relevant because UV-associated cancers typically develop in sparsely haired or hairless regions such as the nose and ventrum, making these areas suitable for targeted sunscreen application. Sunscreens containing non-nanoparticle zinc oxide appear safe for dogs and cats when ingestion is prevented or minimised, whereas the safety of organic UV filters remains unclear due to limited safety data in both humans and animals. Non-nanoparticle titanium dioxide is a possible alternative to zinc oxide and organic filters, but there is currently little information on its safety when ingested by dogs and cats. Overall, the available evidence supports sunscreen as a necessary component of UV-reduction strategies in pets, but substantial research is needed to determine the safety profiles of different UV filters and to establish evidence-based guidelines for their safe use. Full article

Background: The management of diabetic foot disease and knee osteoarthritis (OA) with smart orthotics holds significant importance during the early stages of these conditions, given their potential consequences, including functional impairment, chronic pain, and economic burden. Real-time monitoring of plantar foot pressure enables early detection of abnormal force distribution and gait biomechanics, allowing for the redirection of forces away from affected ulcers or arthritic joints. This is the first systematic review to synthesise clinical evidence for smart orthotics technology with real-time plantar pressure sensor biofeedback across both diabetic foot ulcer prevention and knee osteoarthritis management simultaneously. A search of the PROSPERO register confirmed no existing registration covers this specific combination. Objectives: To examine the clinical evidence for the use of standard and smart orthotics in the prevention and management of diabetic foot ulcers (DFUs) and knee OA, and to evaluate their impact on plantar pressure redistribution, ulcer recurrence, pain, biomechanics, and economic burden. Eligibility criteria: Studies published in English involving human adult participants (≥18 years) with a clinical diagnosis of diabetes mellitus (at risk of DFU or with peripheral neuropathy) or knee OA, where the intervention involved any orthotic device or smart/intelligent insole with clinical outcomes reported, were included. Studies on healthy individuals only, those not reporting participant age, and non-weight-bearing protocols not differentiated from weight-bearing were excluded. Information sources: Five databases were searched: CINAHL (EBSCO Information Services, Ipswich, MA, USA), PubMed Advanced (National Library of Medicine, Bethesda, MD, USA), Wiley Online Library (John Wiley & Sons, Hoboken, NJ, USA), Cochrane Library (Cochrane Collaboration, London, UK), and Google Scholar (Google LLC, Mountain View, CA, USA). Searches were completed in May 2026. Methods: We conducted a comprehensive literature review. This review was structured and reported with reference to the PRISMA 2020 statement (Preferred Reporting Items for Systematic Reviews and Meta-Analysis; University of Ottawa, Ottawa, ON, Canada) to guide transparency of reporting. It does not constitute a full Cochrane-style systematic review; risk of bias assessment was applied to key included studies and GRADE (Grading of Recommendations Assessment, Development and Evaluation; McMaster University, Hamilton, ON, Canada) certainty ratings were applied informally and narratively rather than as formal per-outcome evidence profiles. Five databases were searched yielding 92,637 records. After removal of 398 duplicates by Rayyan, 92,239 records remained. A subsequent automated keyword-based relevance filter applied within Rayyan (Rayyan AI, Doha, Qatar), prior to human screening, excluded 84,572 records that did not contain any terms related to orthotics, diabetic foot, or knee osteoarthritis, yielding 7667 records for human title/abstract screening. A narrative synthesis approach was adopted owing to the heterogeneity of study designs and outcome measures across included studies, which precluded meta-analysis. This review was not prospectively registered. A complete list of all 78 included studies, including those not individually discussed in the results and discussion. Results: The available clinical studies report promising findings for orthotics and smart orthotics in pain reduction, ulcer prevention, and potential reduction in economic burden, though conclusions are limited by small sample sizes, heterogeneity, and predominantly open-label designs. Recent research found that orthotics can be used to alter the gait pattern that influences knee OA by reducing excessive force on the affected joint. A randomised controlled trial demonstrated an 80% relative risk reduction in DFU recurrence (RR = 0.20; 95% CI: 0.06–0.79; p = 0.022), with absolute event rates of 6.3% in the intervention group versus 30.8% in controls (ARR = 24.5%); a second trial reported a 71% reduction in ulcer incidence over 18 months; and a third randomised controlled trial demonstrated statistically significant plantar pressure reduction (p < 0.01) in patients with diabetic neuropathy. Conclusions: The available evidence suggests that orthotics may be associated with improved pressure redistribution, reduced ulcer incidence, and benefit in the management of knee OA. Although the number of studies directly comparing smart orthotics with standard orthotics remains limited, the limited comparative studies suggested that smart orthotics showed promising results in reducing ulcer incidence, providing the patient with real-time feedback to offload via their electronic devices. These findings, while preliminary, highlight the potential of smart orthotic technology as an adjunct to standard orthotic care in reducing the overall burden of diabetic foot disease and knee osteoarthritis. Limitations: The primary methodological limitation of this review is the open-label design of all included smart orthotic trials, which precludes participant blinding and introduces performance bias. However, this limitation is structural and inherent to the wearable technology field—analogous to surgical trials—and is substantially mitigated by the use of objective primary outcome measures (plantar pressure and ulcer recurrence) across the three included RCTs, the consistency of effect direction across independent RCTs conducted in different countries, and a narrative sensitivity analysis confirming robustness of findings (Risk of Bias Across Studies Section). Formal per-outcome GRADE evidence profiles were not produced; overall certainty of evidence was assessed narratively with reference to GRADE domains and is judged to be low to moderate for smart orthotics in DFU prevention and low for knee OA management, consistent with the Level 2–3 evidence base and open-label study designs. Future adequately powered, multi-site RCTs with standardised outcome reporting, minimum 24-month follow-up, and integrated health economic modelling are the highest priority to extend these preliminary findings. Registration: This review was not prospectively registered. Full article

Background: Pericardial involvement is the most common cardiac manifestation of systemic lupus erythematosus (SLE), ranging from mild effusion to recurrent pericarditis and cardiac tamponade. The influence of antiphospholipid syndrome (APS) on lupus-related pericardial disease remains unclear. Methods: A systematic review was conducted in accordance with PRISMA 2020 guidelines and registered in PROSPERO. PubMed, Web of Science, Scopus, and the Cochrane Library were searched from inception to January 2026 for observational studies evaluating pericardial manifestations in adult SLE patients. APS/aPL status was considered a potential modifying factor when reported. Results: Seven observational studies were included. Pericardial involvement ranged from acute and recurrent pericarditis to large effusions and cardiac tamponade. Across studies, it was consistently associated with higher disease activity and markers of immune activation. Recurrent pericarditis emerged as a clinically relevant phenotype linked to more severe disease and worse outcomes. Cardiac tamponade, although rare, was associated with significant morbidity and mortality. APS/aPL-related data were heterogeneous and inconsistently reported across studies. No consistent APS-specific association with pericardial disease could be established, although APS or aPL-related findings were occasionally reported in selected severe or clinically complex presentations. Conclusions: Pericardial involvement in SLE reflects systemic inflammatory burden and spans a broad clinical spectrum. Current evidence regarding APS remains limited and heterogeneous, although APS may contribute to disease complexity in selected severe presentations. Importantly, isolated aPL positivity should not be interpreted as equivalent to formally classified APS. Prospective studies with standardized definitions and systematic assessment of APS are needed. Full article

Background: Non-colorectal cancer liver metastases (NCRLMs) represent a therapeutically challenging condition with poorly defined locoregional treatment options. This study evaluates the safety, oncological efficacy, and survival outcomes of microwave ablation (MWA) for NCRLMs in a large single-centre series. Methods: Retrospective analysis of patients undergoing MWA for NCRLM between January 2010 and December 2024 at a high-volume hepatobiliary centre. Endpoints were safety, efficacy, textbook outcome (TO) achievement, and overall survival (OS). Results: A total of 138 patients underwent 172 MWA procedures across eight primary tumour categories via a video-assisted (n = 110, 64%) or percutaneous (n = 62, 36%) approach. Major complications (Clavien–Dindo ≥ 3) occurred in 1.8% of procedures, with a median hospital stay of 2 days and a 90-day mortality of 1.7%. The median follow-up was 24.9 (10.3, 55.8) months. Complete response (CR) was achieved in 77% of procedures and TO in 54%, with incomplete response as the main driver of TO failure. The 5-year OS varied by histology, from 100% (GIST) and 80.0% (GEP-NET) to 44.7% (breast) and 0% (pancreatic adenocarcinoma). The video-assisted ablation was associated with superior OS compared to the percutaneous one (5-year OS 54.4% vs. 26.0%, p = 0.00025). In the multivariable analysis, the percutaneous approach (HR 2.44), ECOG PS ≥ 2 (HR 6.06) and a higher tumour burden score (HR 1.09) independently predicted worse OS, whereas the histological group was not independently associated with OS. Repeat MWA was the most frequent treatment for first hepatic recurrence, and 50% of patients reached no evidence of disease (NED) at last follow-up. Conclusions: MWA is a safe and repeatable locoregional treatment for NCRLMs, with outcomes shaped by tumour biology, disease burden, patient fitness and procedural approach. The high rate of liver-dominant recurrence treated with repeat MWA, combined with a final NED rate of 50%, supports MWA as a platform for iterative locoregional disease control in selected patients. Full article

Aim: Inflammatory myofibroblastic tumor (IMT) is a rare mesenchymal neoplasm with few reported mandibular cases. This review aims to describe the clinical characteristics, surgical management and outcomes of 13 mandibular IMT cases, and to introduce the Jaw in a Day (JIAD) approach as a novel surgical option. Methods: PubMed, Web of Science and Embase were searched systematically. From an initial pool of 261 articles, 13 studies met the inclusion criteria and were reviewed. Results: Thirteen mandibular IMT cases were identified in the literature. A new case is also presented: a 15-year-old female treated with surgical excision using the JIAD approach. At 12-month follow-up, oral function was restored with no disease recurrence. Discussion: Mandibular IMT is exceedingly rare. The JIAD approach offers immediate reconstruction with satisfactory functional outcomes, as supported by both the current case and the reviewed literature. Conclusions: The JIAD surgical approach may represent an effective management strategy for mandibular IMT. Further cases are needed to validate this approach and establish standardized treatment protocols. Full article

Autophagy-associated readouts in localized prostate cancer cannot be interpreted based on LC3, p62/SQSTM1, or LC3 puncta alone. In line with the concept of autophagy as a stress-response system, this review proposes a flux-aware, organelle-centered framework for assigning biological meaning to autophagy-related changes under disease-relevant stress. The framework integrates oxidative burden, lysosomal competence, selective autophagy, mitophagy, ferritinophagy, p62/SQSTM1-NRF2 signaling, ferroptosis-aware controls, and disease-stage context to distinguish four interpretive states: homeostatic quality control, adaptive tumor survival, blocked clearance, and stress-overload vulnerability. Flavonoid-associated responses are used as stress-test examples because they expose recurrent limitations in the field, including supraphysiologic exposures, limited metabolite realism, static-marker inflation, and insufficient assessment of lysosomal function. However, the framework is not restricted to dietary compounds; it applies to metabolic, pharmacological, inflammatory, androgen-related, radiation-associated, or therapy-induced perturbations in which autophagy-associated markers are altered without resolution of flux or organelle function. By linking autophagosome formation, cargo turnover, lysosomal acidification, redox buffering, and phenotype-level endpoints, this review defines a practical evidence hierarchy for interpreting autophagy in localized prostate cancer and for prioritizing translational vulnerabilities arising from organelle crosstalk. This contribution is primarily conceptual and is operationalized methodologically through flux-based evaluation criteria and translationally through disease-window-specific study-design recommendations. Full article

Background and Clinical Significance: The Coronary Sinus Reducer (CSR) is a percutaneous therapeutic option for patients with refractory angina who are unsuitable for further myocardial revascularization. The procedure has a generally favorable safety profile, with a low rate of reported procedural complications. To our knowledge, major atrioventricular (AV) conduction disturbances during CSR implantation have not been previously described. This case highlights a rare but clinically relevant intraprocedural complication; Case Presentation: A 71-year-old man with multivessel coronary artery disease and previous coronary artery bypass grafting was referred for CSR implantation because of refractory angina despite optimal medical therapy and lack of further revascularization options. The procedure was performed via a right jugular venous approach. Baseline electrocardiography showed right bundle branch block and findings consistent with previous inferior myocardial infarction, without definite criteria for left anterior fascicular block. During coronary sinus cannulation, the patient developed transient complete AV block, resulting in an approximately 8–10-second ventricular pause without a stable ventricular escape rhythm. The conduction disturbance resolved after catheter withdrawal and repositioning. Given the severity of the event, a temporary transvenous pacemaker was inserted via the right femoral vein, allowing safe completion of CSR implantation. At three-month follow-up, angina had improved from Canadian Cardiovascular Society class III to class I, and no recurrent advanced AV block was documented; Conclusions: Transient complete AV block may occur during CSR implantation, particularly during coronary sinus manipulation and possibly in patients with pre-existing conduction disease. Careful catheter handling, prompt recognition of conduction disturbances, and immediate availability of temporary pacing support should be considered in selected high-risk patients undergoing CSR implantation. Full article