Search Results (5,392)

Unc-51-like kinase 3 (ULK3) is a key member of the ULK serine/threonine kinase family. Aberrant ULK3 expression has been increasingly linked to tumorigenesis and malignant progression in multiple cancer types. However, the precise role of ULK3 in tumor initiation and progression remains incompletely understood. Leveraging integrated multi-omics data from The Cancer Genome Atlas (TCGA), the Genotype-Tissue Expression (GTEx) project, and the Clinical Proteomic Tumor Analysis Consortium (CPTAC), we systematically characterized the expression of ULK3 at both the transcript and protein levels across 33 cancer types. We also evaluated genomic alterations, prognostic significance, alternative splicing, pathway enrichment, tumor stemness, immune infiltration, and immunotherapy-related biomarkers. In parallel, we investigated the function of ULK3 in prostate cancer PC-3 cells using cellular localization analysis, wound-healing assays, and MTT assays. We further applied Connectivity Map (CMap) screening and molecular docking to identify candidate ULK3 activators. ULK3 was significantly upregulated in 13 cancer types, including Bladder Urothelial Carcinoma, Breast Invasive Carcinoma, and Lung Adenocarcinoma. In contrast, ULK3 was downregulated in Cholangiocarcinoma and Head and Neck Squamous Cell Carcinoma. High ULK3 expression was associated with poor overall survival in Adrenocortical Carcinoma, Kidney Renal Clear Cell Carcinoma, and Skin Cutaneous Melanoma. Copy number amplification contributed to ULK3 overexpression. A recurrent A206V missense mutation was detected in the protein kinase (Pkinase) domain. Genes co-expressed with ULK3 were enriched in RNA splicing, methylation, oxidative phosphorylation, and energy metabolism. ULK3 expression showed positive correlations with tumor stemness indices and m1A/m5C/m6A RNA modification regulators. From an immunological perspective, high ULK3 expression was associated with lower Immune Score, increased M2 macrophage infiltration, and co-expression of PD-L1, CTLA4, and LAG3 in most cancers. ULK3 expression was also correlated with Tumor Mutational Burden in Kidney Renal Clear Cell Carcinoma and Rectum Adenocarcinoma. In addition, ULK3 expression was associated with Microsatellite Instability in Brain Lower Grade Glioma, Lung Adenocarcinoma, and Uterine Corpus Endometrial Carcinoma. ULK3 overexpression promoted proliferation and migration in PC-3 cells. Cephaeline was screened as a putative ULK3 activator. Overall, ULK3 expression and amplification were associated with poor clinical outcomes, tumor stemness, immunosuppression, and RNA dysregulation. These findings highlight the potential value of ULK3 as a pan-cancer diagnostic and prognostic biomarker and as a predictor of immunotherapy response, particularly in prostate cancer. Full article

Glioblastoma multiforme (GBM), isocitrate dehydrogenase (IDH)-wildtype, is the most aggressive primary malignant tumor of the central nervous system, characterized by poor prognosis and high recurrence rates despite standard multimodal treatment. This study investigates the molecular response of glioblastoma cells to 5-aminolevulinic acid (5-ALA)-based photodynamic therapy (PDT), focusing on gene expression changes associated with apoptosis, ferroptosis, and oxidative stress. Human glioblastoma T98G cells were treated with 5-ALA followed by light irradiation, and gene expression was analyzed using RT-qPCR. PDT induced moderate upregulation of pro-apoptotic genes (BAX, CASP3, FAS) alongside increased expression of the anti-apoptotic gene BCL2, indicating simultaneous activation of cell death and survival pathways. Ferroptosis-related genes showed mixed responses, with slight upregulation of ACSL4 and downregulation of GPX4, suggesting increased susceptibility to lipid peroxidation. The most significant change was observed in GCH1 expression, reflecting activation of oxidative stress response mechanisms. However, none of the observed changes reached statistical significance, likely due to the limited sample size. These findings demonstrate that PDT induces a complex and dual biological response in glioblastoma cells, involving both cytotoxic and adaptive mechanisms. This may limit therapeutic efficacy and contribute to treatment resistance. The results support the rationale for combining PDT with targeted molecular therapies aimed at inhibiting antioxidant defenses and anti-apoptotic pathways. Additionally, personalized therapeutic strategies based on tumor molecular profiles may enhance treatment outcomes. Further studies with larger sample sizes and functional validation are required to confirm these preliminary observations. Full article

Background and Objectives: Extramammary Paget’s Disease (EMPD) of the perineal region is a rare intraepidermal adenocarcinoma requiring wide excision, resulting in extensive defects that are challenging to reconstruct while preserving contour and function. This descriptive case series evaluated a reconstructive selection strategy using pedicled superficial circumflex iliac artery perforator (SCIP) flaps and pedicled anterolateral thigh (ALT) flaps for perineal defects following wide excision of EMPD. Materials and Methods: This retrospective case series reviewed patients with perineal EMPD who underwent wide excision followed by reconstruction using pedicled SCIP flaps or pedicled ALT flaps. Patient demographic and lesion characteristics, operative and flap characteristics, post-reconstruction complications, oncologic outcomes, and satisfaction were analyzed. Results: 15 patients (mean age 63 years, SD 7.3) were included in this case series. Ten patients underwent reconstruction using pedicled SCIP flaps (mean 106 cm², SD 23.3), and five patients with pedicled ALT flaps (mean 245.2 cm², SD 41.2). All flaps survived, but one patient developed limited partial necrosis managed with secondary healing. During a mean follow-up of 17.7 months (SD 1.3), one patient (6.7%) developed recurrence and eventually distant metastasis resulting in death. Among the 14 surviving patients, 13 (92.9%) reported overall satisfaction with cosmetic and functional outcomes assessed using a non-validated ordinal scale. Conclusions: Pedicled SCIP and ALT flap reconstruction provides reliable, well-vascularized tissue coverage for perineal EMPD defects and achieves generally favorable short-term outcomes. The choice between flap types should be tailored to the defect size, location, and patient characteristics. Full article

Background: Urolithiasis is a common condition characterized by a high risk of recurrence, although this risk varies substantially between patients. The present study aimed to quantify incidence, identify determinants, and model recurrence risk between stone composition and recurrence, and to assess the role of selected clinical and behavioral factors in a cohort of patients with confirmed stone clearance. Methods: This retrospective cohort study included adult patients with urolithiasis managed between 2017 and 2021 in a specialized referral center. Only patients with confirmed stone-free status and available follow-up were included. Stone composition was determined using morpho-spectroscopic analysis. Clinical and behavioral variables were collected from medical records. Recurrence was defined as a new stone event during follow-up. Time-to-event analysis was performed using Kaplan–Meier estimates and Cox proportional hazards models. Results: A total of 962 patients were included, with a median follow-up of over three years. During this period, recurrence occurred in approximately one-third of patients. Uric acid stones were associated with a higher risk of recurrence compared with calcium oxalate monohydrate stones, while the effect size was moderate. Previous stone history and low fluid intake were also independently associated with recurrence. Other dietary variables did not retain statistical significance after adjustment. Conclusions: Recurrence in urolithiasis appears to reflect the combined effect of compositional, clinical, and behavioral factors. While certain variables are associated with increased risk, no single determinant fully explains recurrence patterns. These findings support a more individualized approach to risk assessment and follow-up. Full article

Background: Early recurrence following curative-intent hepatectomy for colorectal liver metastases (CRLMs) remains a significant clinical challenge. This study investigates risk factors for recurrence within 6 and 12 months and evaluates the impact of salvage surgery on long-term survival. Methods: We conducted a retrospective cohort study of 109 patients who underwent liver resection for CRLMs between 2013 and 2024. The primary outcome was the identification of predictors for early recurrence using Cox proportional-hazards models. The secondary outcomes focused on overall survival (OS) stratified by the timing of recurrence and subsequent treatment. Results: High tumor burden (>4 metastases) was an independent predictor of recurrence at both 6 months (HR 3.526; p = 0.008) and 12 months (HR 3.115; p = 0.004). Intraoperative blood loss >1000 mL was significantly associated with 6-month recurrence (HR 3.356; p = 0.004) and 12-month recurrence (HR 2.171; p = 0.041). For the 12-month window, independent predictors included AJCC T3/T4 stage (HR 6.513; p = 0.011) and RAS mutation (HR 2.740; p = 0.006). Notably, patients with early recurrence who underwent salvage re-hepatectomy achieved 5-year OS rates that did not statistically differ from those without recurrence (p = 0.907 for <6 months; p = 0.433 for <12 months); however, these subgroup analyses are highly underpowered. Conclusions: High tumor burden (>4 metastases), RAS mutations, significant blood loss (>1000 mL), and primary tumor T3/T4 identify patients at high risk for early recurrence. While aggressive salvage re-hepatectomy is associated with prolonged survival in select patients, the non-significant p-values in our small salvage cohorts cannot be interpreted as evidence of survival equivalence. The observed survival benefits in the salvage cohort are heavily confounded by inherent selection biases, and therefore, the true extent of this ‘rescue’ effect must be interpreted with extreme caution and validated in larger, adequately powered multicenter studies. Full article

MR-guided adaptive radiotherapy (ART) enables daily plan optimization for prostate cancer but is resource-intensive. This study evaluated dosimetric and clinical outcomes following transition from radiation oncologist (RO)-led to radiation therapist (RTT)-led MR-guided ART. All prostate cancer patients treated with MR-guided ART on a 1.5T MR-linac were retrospectively reviewed. Consecutive RO-led (September 2019–November 2021) and RTT-led (April 2022–October 2023) cohorts were compared, excluding the actual transition period. Toxicities (CTCAE v5.0), dose–volume metrics from daily adapted plans, target volume variation, and biochemical recurrence-free survival (BRFS) were analyzed. A total of 166 patients were included (78 RO-led, 88 RTT-led; median follow-up 40 and 35 months). Dosimetric differences between the cohorts were statistically small (<1%). Rates of G2+ GI adverse events were similar across all timepoints. An increase in on-treatment GU events was observed in the RTT-led cohort (G2+ 27% vs. 9%, G3 incidence n = 2 vs. n = 0), likely reflecting higher baseline urinary dysfunction; no post-treatment differences persisted. Early biochemical outcomes were comparable, with 36-month BRFS of 93.5% (RO-led) and 95.0% (RTT-led). RTT-led MR-guided ART achieved comparable dosimetric quality and early biochemical outcomes to RO-led workflows with adverse advents that resolved in the long term. With structured training and a mature practice setting, RTT-led ART represents a scalable model to support future adaptive radiotherapy practice. Full article

Burkitt lymphoma (BL) is an aggressive B-cell lymphoma endemic in children in regions of sub-Saharan Africa, where its incidence geographically overlaps holoendemic Plasmodium falciparum malaria and poorly controlled childhood Epstein–Barr virus (EBV) infection. Despite decades of research, the precise mechanistic synergy between these two pathogens remains incompletely defined. This review synthesizes current epidemiological, immunological, and molecular evidence to propose an integrated model for the etiology of endemic BL. We outline a paradoxical, dual-edged relationship wherein EBV infection during infancy may provide a short-term child survival advantage against severe malaria while simultaneously increasing the long-term oncogenic risk in B-cells infected by EBV. P. falciparum infection triggers polyclonal B-cell activation, increasing the probability of an activation-induced cytidine deaminase (AID)-mediated c-MYC translocation in proportion to the recurrent parasite burden. Concurrently, EBV expands within this B-cell pool and modulates the host immune response, potentially through viral interleukin-10 (vIL-10), to prevent lethal malarial inflammation. At the cellular level, EBV provides a critical “second hit” when it establishes latency I infection that rescues c-MYC-translocated B-cells from apoptosis. This framework explains why BL manifests as a “tumor of malaria survivors,” peaking in incidence years after the highest-risk period for malaria mortality. Ultimately, this model underscores that malaria control is a critical form of cancer control and highlights key future directions for validating these pathways in prospective clinical studies. Full article

Background/Objectives: Non-muscle invasive bladder cancer (NMIBC) is characterized by high recurrence rates despite appropriate treatment and surveillance. Identifying inexpensive and readily available biomarkers capable of improving risk stratification remains an important clinical challenge. The platelet-to-lymphocyte ratio (PLR), a marker of systemic inflammation, has emerged as a potential prognostic indicator in several malignancies. This study aimed to evaluate the association between preoperative PLR, tumor recurrence, and recurrence-free survival (RFS) in NMIBC patients treated with intravesical Bacillus Calmette–Guérin (BCG) or thermochemotherapy. Methods: This retrospective study included 153 patients diagnosed with NMIBC between January 2020 and January 2024. All patients underwent transurethral resection of bladder tumor (TURBT) followed by intravesical BCG (n = 123) or thermochemotherapy (n = 30). Preoperative PLR was calculated from complete blood counts obtained before surgery. Receiver operating characteristic (ROC) analysis was used to determine the optimal PLR cut-off value. Recurrence-free survival was evaluated using Kaplan–Meier survival analysis and Cox proportional hazards regression models. Results: During a mean follow-up period of approximately 19 months, recurrence was observed in 35.8% of patients treated with BCG and 30% of those treated with thermochemotherapy. ROC analysis demonstrated good discriminatory ability for recurrence prediction (AUC = 0.831, 95% CI: 0.761–0.901, p < 0.001) and identified an optimal PLR threshold of 120. Patients with elevated PLR values demonstrated higher recurrence rates and shorter recurrence-free survival. Kaplan–Meier analysis revealed a clear separation of survival curves according to PLR status. In multivariable Cox regression analysis, PLR > 120 remained independently associated with recurrence-free survival in the BCG group (HR = 2.703, 95% CI: 1.118–6.534, p = 0.027), whereas only a borderline association was observed in the thermochemotherapy group (HR = 23.265, 95% CI: 0.952–568.336, p = 0.054). Conclusions: Elevated preoperative PLR was associated with recurrence and recurrence-free survival in patients with NMIBC. The prognostic value of PLR appeared to be more pronounced in patients receiving intravesical BCG therapy. Given its low cost, accessibility, and ease of calculation, PLR may serve as a useful adjunctive biomarker for clinical risk stratification when used alongside established clinicopathological prognostic factors. Further prospective multicenter studies are required to validate these findings. Full article

Background/Objectives: Following the LACC trial, the role of minimally invasive radical surgery for early-stage cervical cancer remains controversial. Robotic-assisted approaches have been proposed as a potential strategy to preserve the benefits of minimally invasive surgery while incorporating contemporary oncologic precautions. This study compared perioperative, pathological, and early oncologic outcomes between robotic and open radical surgical management in patients with FIGO 2018 stage IA2–IIA1 cervical cancer. Methods: Patients underwent robotic surgery (n = 20; da Vinci Xi), including robotic radical hysterectomy, compartment-based procedures, and fertility-sparing surgery when clinically indicated, or open abdominal radical hysterectomy (n = 22). Perioperative outcomes, histopathological parameters (including lymphovascular space invasion [LVSI], lymph node status, and margin status), and early oncologic outcomes were evaluated. Exploratory multivariable regression analyses were performed to adjust for baseline differences, including age and tumor size. Results: Patients in the open-surgery cohort were older (56.23 ± 15.87 vs. 45.67 ± 9.31 years; p = 0.012) and had significantly larger tumors (3.07 ± 1.10 vs. 1.4 ± 0.7 cm; p = 0.003). Robotic surgery was associated with longer operative time (178 ± 42 vs. 150 ± 38 min; p = 0.028), lower blood loss (112 ± 61 vs. 518 ± 98 mL; p < 0.001), and shorter hospital stay (4.2 ± 1.6 vs. 6.2 ± 1.4 days; p < 0.001). The robotic cohort also demonstrated a higher lymph node yield (median 18 vs. 9; p < 0.001). No statistically significant differences were observed between groups in lymph node metastasis (20.0% vs. 22.7%; p = 1.000), LVSI (33.3% vs. 63.6%; p = 0.121), or R0 resection rate (100% vs. 95.5%; p = 1.000). In exploratory adjusted analyses, surgical approach was not associated with adverse pathological features, whereas tumor size emerged as an independent predictor of both lymph node metastasis and LVSI. No recurrences were observed in the robotic cohort during the available follow-up period. Conclusions: In this exploratory comparative cohort study, robotic radical surgical management in carefully selected patients with predominantly small-volume disease was associated with favorable perioperative outcomes and no statistically significant differences in pathological parameters compared with open surgery. Tumor size, rather than surgical approach, emerged as the principal predictor of adverse pathological features. Given the limited sample size, baseline imbalances between cohorts, heterogeneous robotic procedures, and absence of mature survival data, these findings should not be interpreted as evidence of oncologic equivalence and require confirmation in larger prospective studies. Full article

Backgrounds: Bladder cancer shows pronounced biological heterogeneity that underlies its variable clinical course and prognosis. Our study aims to delineate clinically relevant differences in bladder cancer using an immunohistochemistry-based molecular subtyping approach. Methods: This retrospective study included 590 patients with bladder cancer treated at a single center. Tumors were stratified into luminal versus non-luminal categories according to CK20, GATA3, CK5/6, and CK14. Associations between molecular subtype, histopathological growth patterns, pathological response to neoadjuvant chemotherapy (NAC), and clinical survival endpoints were analyzed. Overall survival (OS), recurrence-free survival (RFS), and progression-free survival (PFS) were evaluated through Kaplan–Meier survival curves together with Cox proportional hazards regression analyses. Results: Non-luminal tumors exhibited significantly more aggressive pathological growth patterns, including higher levels of tumor budding (p = 0.002), a predominance of non-cohesive or spindle/single-cell architecture (p = 0.003), and more frequent disseminated spreading patterns (p = 0.001), whereas luminal tumors more commonly displayed a higher frequency of tertiary lymphoid structures (TLSs; p = 0.041). Among patients receiving NAC, non-luminal tumors achieved a significantly higher pathological complete response (pCR) rate compared with luminal tumors (p = 0.007), while no significant inter-subtype difference was detected in pathological downstaging between subtypes (p = 0.126). Despite inferior pathological response, luminal tumors demonstrated significantly improved OS (p = 0.003), RFS (p = 0.002) and PFS (p < 0.001) compared with non-luminal tumors. In multivariable Cox regression analysis, molecular subtype was identified as an independent predictor of OS, with luminal tumors showing a lower mortality risk (HR = 0.51, 95% CI 0.33–0.79, p = 0.003). Conclusions: These findings indicate that pathological response and long-term survival follow distinct, subtype-dependent trajectories in bladder cancer. Favorable pathological response does not necessarily correspond to improved long-term survival across molecular subtypes. Full article

Background/Objectives: Acute cholecystitis is a common surgical emergency associated with significant morbidity in elderly, frail, and critically ill poor surgical candidates. Early laparoscopic cholecystectomy remains the standard of care for low-risk patients, but interventional radiology (IR) modalities have been increasingly used in high-risk patients for gallbladder decompression, source control, and/or definitive non-operative treatment. Methods: A narrative review of the literature was performed to investigate current percutaneous IR options in acute cholecystitis. Evidence from international guidelines, randomized trials, systematic reviews, meta-analyses, and experimental novel techniques were reviewed. The patient selection approaches, timing of intervention, efficacy, complications, and risk of recurrence were summarized. Results: Percutaneous cholecystostomy remains the most commonly performed IR procedure for acute cholecystitis, offering decompression and source control in patients unfit for surgery. Percutaneous gallstone extraction and gallbladder chemical ablation, or cryoablation, have been used to reduce recurrence and long-term catheter dependence with promising results, but are still limited by complications and insufficient evidence. The variability in practice patterns and the absence of standardized treatment algorithms contribute to mixed results, ranging from long-term/definitive symptom control to the prolonged dependence on indwelling catheters and readmissions for catheter-related complications. Conclusions: IR plays an important role in the management of high-risk patients with acute cholecystitis. The careful selection of patients based on disease severity, physiologic reserve, frailty, and patient-centered goals is frequently limited by institutional resources. A structured clinical decision framework to guide IR-based interventions in acute cholecystitis is of the utmost importance to achieve optimal outcomes. Future studies should focus on standardized algorithms, patient-centered outcomes, recurrence, tube-free survival, and quality of life. Full article

Ovarian cancer is a major cause of gynecological cancer mortality, frequently associated with platinum-resistant recurrences. Given the limited efficacy of conventional chemotherapy in this setting, alternative targeted therapeutics are needed. Mirvetuximab soravtansine (MIRV) is an antibody–drug conjugate designed to deliver the cytotoxic maytansinoid DM4 to folate receptor alpha (FRα)-overexpressing cells. This systematic review of PubMed, ClinicalKey, and SpringerLink databases (2019–2026) evaluates five publications across three clinical trials (one phase II, two phase III) encompassing 925 patients with platinum-resistant disease. Notably, the phase III MIRASOL trial demonstrated improved survival outcomes with MIRV over standard chemotherapy, extending median overall survival (16.46 vs. 12.75 months; HR 0.67) and progression-free survival (5.62 vs. 3.98 months; HR 0.65), with an objective response rate (ORR) of 42.3% versus 15.9%. Furthermore, the single-arm phase II SORAYA trial reported an ORR of 32.4% in pretreated patients, including those with prior PARP inhibitor and bevacizumab exposure. Although the preceding FORWARD I trial missed its primary endpoint in the unselected population, its high-FRα subgroup analysis revealed a clinical benefit that influenced subsequent biomarker-driven enrollment strategies. From a safety perspective, MIRV exhibited lower rates of severe neutropenia and anemia than chemotherapy, with toxicities primarily consisting of manageable, reversible ocular events. Ultimately, MIRV serves as a therapeutic option for platinum-resistant, FRα-positive ovarian cancer, offering survival advantages; however, rigorous biomarker-based screening remains necessary to optimize therapeutic outcomes. Full article

Background: This study aimed to compare the outcomes and safety profiles of total neoadjuvant therapy (TNT) combined with dose-escalated intensity-modulated radiotherapy (IMRT) and conventional neoadjuvant chemoradiotherapy (NACRT) using three-dimensional conformal radiotherapy (3D-CRT) for locally advanced lower rectal cancer. Methods: This single-institution retrospective study included 51 patients treated with TNT using IMRT from 2018 to 2023 and 53 patients treated with conventional NACRT from 2001 to 2018. TNT consisted of IMRT at a total dose of 54 Gy with capecitabine, whereas NACRT consisted of 3D-CRT at a total dose of 45 Gy with a 5-fluorouracil-based regimen. Survival outcomes, treatment compliance, adverse events, surgical complications, and combined complete response (CR), defined as clinical CR plus pathological CR, were evaluated. Results: The combined CR rate was significantly higher in the TNT with IMRT group than in the NACRT group (43.1% vs. 5.7%). Overall survival and local recurrence-free survival did not differ significantly between the groups, whereas recurrence-free survival was significantly better in the TNT with IMRT group. Treatment compliance was comparable between the groups. Grade ≥ 3 adverse events during radiotherapy were less frequent in the TNT with IMRT group than in the NACRT group (7.8% vs. 22%), and major surgical complications did not differ significantly. Conclusions: TNT combined with dose-escalated IMRT was associated with a higher combined CR rate, favorable disease-free survival, and acceptable toxicity in this cohort. However, given the retrospective historical control design, chronological differences, follow-up imbalance, and potential residual confounding, these findings should be interpreted cautiously and require validation in prospective studies with longer follow-up. Full article

The biggest challenge faced by classical anticancer therapy is drug resistance, which causes cancer recurrence and metastasis. Two underlying mechanisms could be responsible, including the stemness of pro-survival autophagy-associated cancer stem cells (CSCs). Background/Objectives: The relationship between CSCs and autophagy in gynecological cancer is still unknown. However, it has been shown that CSCs’ in vitro self-renewal ability is decreased when autophagy is inhibited. Helping to maintain normal tissue homeostasis, autophagy is a catabolic process involved in degrading long-lived proteins and cytoplasmic organelles. Autophagy acts as a key player in the human body’s self-regenerating tissues. It also has a reproductive function, contributing to decidualization for a successful pregnancy. The aim of our review is to identify similarities and differences between these processes, using these findings to discover new therapeutic strategies through nanotechnology. Method: We conducted a narrative review, identifying heterogeneity in the data in the literature, and found 153 relevant articles. Discussions: While autophagy has been proven to be capable of acting as a tumor suppressor, it also promotes tumor progression. Moreover, it has been linked to cancer stem cell regulation, therapy resistance, cancer invasion, and metastasis. Several molecular mechanisms have been linked to autophagy. Remarkably, some cellular processes required for proper placentation, including autophagy, are common between placental development and tumor growth. Just as trophoblast cells invade and migrate, so do cancer cells. While in the trophoblast, this phenomenon is programmed and controlled; in cancer, this regulation is lost. As shown, we thus observed commonalities and discrepancies in the phenotypes and underlying molecular mechanisms of autophagy regulation in preeclampsia versus cancer contexts. Translational applicability of nanomedicine research strategies and design paradigms between preeclampsia intervention and cancer therapy has been sought. Conclusions: Autophagy-based nanotechnology seems to be feasible in both placental ischemia in preeclampsia and cancers. This review draws parallels between targeted treatments in malignancies and placenta-derived PE. Comparing these diseases provides a novel molecular rationale and the possibility of identifying treatment through autophagy modulation. Full article

Background: Chronic obstructive pulmonary disease (COPD) and tuberculosis (TB) are among the most prevalent respiratory disorders worldwide and frequently coexist in the same patient. However, the contribution of active TB and post-tuberculosis lung disease to COPD exacerbations and long-term prognosis remains incompletely defined. Objective: To evaluate the prevalence, clinical correlates, and prognostic significance of tuberculosis and its sequelae in patients with COPD. Materials and methods: We conducted a population-based retrospective cohort study using de-identified data from the regional healthcare information system. The cohort included all adults aged 18 years or older with a recorded diagnosis of COPD (ICD-10 code J44). Tuberculosis was identified by codes A15–A19 and B90. The primary outcomes were COPD exacerbations and all-cause mortality. Group comparisons, cluster analysis, Kaplan–Meier survival analysis, Cox proportional hazards modeling, and multivariable logistic regression were performed. Results: Tuberculosis and/or its sequelae were identified in 267 of 16,714 patients (1.60%): post-TB sequelae (B90) in 197 (73.8%), active TB (A15–A19) in 22 (8.2%), and both in 48 (18.0%). Compared with patients without TB, those with COPD-TB were younger (63.5 ± 14.2 vs. 65.7 ± 14.7 years; p = 0.018), more often male (75.3% vs. 52.0%; p < 0.001), and had higher mortality (16.5% vs. 10.6%; p = 0.003). COPD-TB was associated with bronchiectasis (OR = 6.07; 95% CI, 3.03–12.16), pulmonary fibrosis (OR = 5.67; 95% CI, 3.40–9.45), and pneumonia (OR = 2.01; 95% CI, 1.50–2.71), but with lower prevalences of obesity, diabetes mellitus, and hypertension. Patients with TB experienced more COPD exacerbations, including recurrent exacerbations. In multivariable models, tuberculosis was associated with COPD exacerbations after adjustment for age and sex (adjusted OR = 1.43; 95% CI, 1.05–1.96); this association was attenuated and lost significance after further adjustment for post-tuberculosis structural lung disease, indicating that it is largely mediated by post-TB sequelae. Tuberculosis remained associated with mortality after adjustment for available covariates, both in logistic regression (adjusted OR = 1.61; 95% CI, 1.14–2.28) and in Cox analysis (hazard ratio = 1.37; 95% CI, 1.01–1.85). Conclusions: Tuberculosis and post-tuberculosis lung disease are clinically accessible risk markers associated with COPD exacerbations and mortality. These findings support recognizing patients with COPD and a history of TB as a high-risk subgroup requiring intensified follow-up, proactive exacerbation prevention, and prioritized vaccination counseling. In the context of personalized medicine, a documented history of tuberculosis and post-tuberculosis lung changes represents a clinically accessible marker that can be used to stratify individual risk and to tailor monitoring and prevention in patients with COPD. Full article