High Recurrence Research Articles

Programmed Death-Ligand 1 (PD-L1) and Ki-67 Labeling Index: Correlation with Tumor Grade and Recurrence

Background: Meningiomas are common primary brain tumors with variable clinical behavior. While most are benign, a subset exhibits aggressive characteristics and a high recurrence rate. This study aimed to investigate the association of Programmed Death-Ligand 1 (PD-L1) and Ki-67 labeling index with histopathological grade and recurrence in meningioma. Methods: A retrospective study was conducted on 139 cases of meningioma diagnosed between January 2020 and December 2023. PD-L1 expression was evaluated using immunohistochemistry (IHC) and scored using the combined positive score (CPS). Ki-67 labeling index was determined as the percentage of tumor cells with positive nuclear staining. The association of PD-L1 and Ki-67 with histopathological grade and recurrence was analyzed. Results: PD-L1 expression was positive in 66.7% of cases and was significantly associated with recurrence (p = 0.006). A higher Ki-67 labeling index (>4%) was observed in 68.9% of cases and was also significantly associated with recurrence (p = 0.013). No significant association was found between PD-L1 expression or Ki-67 labeling index and histopathological grade. Conclusion: PD-L1 expression and Ki-67 labeling index may serve as potential prognostic markers for predicting recurrence in meningioma. Further studies are needed to validate these findings and explore their potential therapeutic implications.

Myofibroblastic Sarcoma of the Maxillary Sinus: Very Rare Entity

Introduction: The Myofibroblastic Sarcoma is a recently discovered malignant tumor that mainly affects the face and neck region, but it occurs most often in the tongue and oral cavity. However, involvement of the maxillary sinus has only been reported a few times in the literature. It is a slowly growing neoplasm with a high recurrence and metastasis risk.  Case Presentation: 18 years old female patient, admitted for a painless mass of the left hemi palate increasing progressively in volume evolving since 5 months, associated to a left nasal obstruction and purulent rhinorrhea. Once in our department, she underwent a facial CT scan, followed by a facial MRI, which showed a tissue process centered primarily on the left maxillary sinus, causing lysis of the inferior wall and bulging of the hard palate on the left side . The surgical decision involved combining an endoscopic and external approach, and was supplemented by radiation therapy. The follow up demonstrated a successful outcome. the patient did not present any recurrence or distant metastasis.  Conclusion: The key lessons are the essential role of imaging in diagnosing and treating LGMS , as well as the crucial role of postoperative radiotherapy in preventing recurrence even though this subject is still controversial.

Endogenous Magnetic Lipid Droplet-Mediated Cascade-Targeted Sonodynamic Therapy as an Approach to Reversing Breast Cancer Multidrug Resistance.

Multidrug resistance (MDR) has emerged as a major barrier to effective breast cancer treatment, contributing to high rates of chemotherapy failure and disease recurrence. There is thus a pressing need to overcome MDR and to facilitate the efficient and precise treatment of breast cancer in a targeted manner. In this study, endogenous functional lipid droplets (IR780@LDs-Fe3O4/OA) were developed and used to effectively overcome the limited diffusion distance of reactive oxygen species owing to their amenability to cascade-targeted delivery, thereby facilitating precise and effective sonodynamic therapy (SDT) for MDR breast cancer. Initially, IR780@LDs-Fe3O4/OA was efficiently enriched within tumor sites in a static magnetic field, achieving the visualization of tumor treatment. Subsequently, the cascade-targeted SDT combined with the Fenton effect induced lysosome membrane permeabilization and relieved lysosomal sequestration, thus elevating drug concentration at the target site. This treatment approach also suppressed ATP production, thereby inhibiting P-glycoprotein-mediated chemotherapeutic drug efflux. This cascade-targeted SDT strategy significantly increased the sensitivity of MDR cells to doxorubicin, increasing the IC50 value of doxorubicin by approximately 10-fold. Moreover, the cascade-targeted SDT also altered the gene expression profiles of MDR cells and suppressed the expression of MDR-related genes. In light of these promising results, the combination of cascade-targeted SDT and conventional chemotherapy holds great clinical promise as an effective treatment modality with excellent biocompatibility that can improve MDR breast cancer patient outcomes.

Non-invasive miRNAs for early detection and diagnosis of lacrimal adenoid cystic carcinoma.

Lacrimal adenoid cystic carcinoma (LACC) is one of the most common malignant epithelial tumors of the lacrimal gland, characterized by high rates of local recurrence, distant metastases, and tumor-related mortality. This malignancy impairs the lacrimal gland's ability to secret tears, thereby disrupting the normal function of the ocular surface. Due to ineffective diagnostic approaches and the complex anatomical location of the lacrimal gland within the orbit, many LACC patients are often diagnosed at the later stages. Therefore, it is urgent to develop a simple and convenient method for early detection of LACC through biomarker analysis by liquid biopsies, such as blood or tears. Various microRNAs (miRNAs) derived from liquid biopsies have been shown to serve as biomarkers for early diagnosis of tumors. In the present study, we screened LACC-specific miRNAs using miRNA microarray analysis in both primary and recurrent patient groups. We then validate their expression by qPCR experiments conducted in tissues, cell lines, tear fluid and serum to explore the association between these miRNAs and LACC development and prognosis. Our findings reveal that hsa-miR-200b-3p, hsa-miR-200c-3p and hsa-miR-141-3p are significantly upregulated in LACC, and the microarray data showed that these three miRNAs were significantly elevated in the recurrence group compared to the primary group. In conclusion, detecting miRNA expression in tear fluid and serum provides non-invasive biomarkers for the early diagnosis of LACC and may facilitate monitoring outcomes related to lacrimal gland diseases.

Perfusable Plasma‐Activated Saline for Oxidative Stress Delivery to Induce Tumor Cell Apoptosis in Nonmuscle‐Invasive Bladder Cancer

ABSTRACTNonmuscle‐invasive bladder cancer (NMIBC) is a common urologic malignancy. Currently, conventional postoperative perfusion therapy for NMIBC still has high side effects and recurrence rates. Cold atmospheric plasma is a fledgling reactive oxygen species (ROS)–based therapeutic technique for cancer treatment. In this study, we examined the feasibility of plasma‐activated saline (PAS) perfusion for treating NMIBC. The results show that underwater bubble plasma can generate abundant ROS in PAS. In vitro studies revealed that PAS could trigger apoptosis in bladder cancer T24 cells by activating the ROS‐mediated caspase‐3 cascade reaction. In vivo tests revealed that intravesical PAS perfusion effectively inhibited nonmuscle‐invasive T24 tumor growth without significant side effects. Therefore, our results suggest that intravesical PAS perfusion may be a novel treatment option for NMIBC.

Clinical features and surgical outcomes of membranous subaortic stenosis in three siblings: a case series and literature review

Introduction: Subvalvular aortic stenosis (SAS) is a rare heart condition that can cause LVOT obstruction and lead to serious complications. While surgery is the main treatment, recurrence is a concern. This case series highlights the challenges in managing SAS in young patients. Case Series: Three young brothers presented with symptoms of shortness of breath and chest tightness. All were diagnosed with membranous SAS through echocardiography and Doppler ultrasound. Surgical intervention was performed to remove the obstruction, but all three patients experienced recurrence within two years. Discussion: This case series of three brothers suggests a genetic predisposition. Symptoms included exertional dyspnea and chest tightness, diagnosed via echocardiography. Surgical intervention is the primary treatment, but its timing is debated due to recurrence risks and complications. Conclusions: This case series suggests a possible genetic predisposition to SAS. Despite successful initial surgery, the high recurrence rate highlights the need for improved management strategies and long-term follow-up. Further research is crucial to understand the causes of recurrence and optimize treatment for children with SAS.

Issues and Countermeasures in Chinese FLTRP Primary School Textbooks under the New Curriculum Standard

The New Curriculum Standard (NCS) is the norm and quality requirement of the Chinese national educational curriculum as well as the basis of teaching management, curriculum evaluation, and textbook compilation. In textbook design, the selection of textbook materials should meet the objectives and requirements of the NCS. Since appropriate teaching materials are essential to curriculum standards and effective teaching, we must follow the consistency between textbook materials and curriculum standards to achieve an ideal degree of conformity with the textbook system and teaching objectives and promote the sustainable development of the English curriculum reform. However, the current primary school English textbooks fall short of the NCS, which leads to difficulties in implementing teaching tasks and achieving teaching goals. Given these difficulties, we should analyze the causes from three dimensions: linguistic knowledge, cultural awareness, and learning strategies. In addition, a high recurrence of phonetic knowledge, systematic grammar presentation, diversified learning styles, level grading, and in-depth involvement of cultural factors are keys to the perfect conformity of the NCS and English textbooks.

Breast cancer secretes anti-ferroptotic MUFAs and depends on selenoprotein synthesis for metastasis.

The limited availability of therapeutic options for patients with triple-negative breast cancer (TNBC) contributes to the high rate of metastatic recurrence and poor prognosis. Ferroptosis is a type of cell death caused by iron-dependent lipid peroxidation and counteracted by the antioxidant activity of the selenoprotein GPX4. Here, we show that TNBC cells secrete an anti-ferroptotic factor in the extracellular environment when cultured at high cell densities but are primed to ferroptosis when forming colonies at low density. We found that secretion of the anti-ferroptotic factors, identified as monounsaturated fatty acid (MUFA) containing lipids, and the vulnerability to ferroptosis of single cells depends on the low expression of stearyl-CoA desaturase (SCD) that is proportional to cell density. Finally, we show that the inhibition of Sec-tRNAsec biosynthesis, an essential step for selenoprotein production, causes ferroptosis and impairs the lung seeding of circulating TNBC cells that are no longer protected by the MUFA-rich environment of the primary tumour.

Molecular mechanisms of resistance and new therapeutic approaches in the treatment of colorectal cancer - a review of the literature

CRC occupies one of the leading positions among gastrointestinal malignancies and is a significant problem in Europe since it is the third most frequently diagnosed cancer. Recent developments in diagnostic techniques have led to higher chances of early diagnosis and survival; nevertheless, CRC is highly likely to relapse in the survivorably younger individuals. The importance of the current chemotherapy treatment and potential key therapeutic targets are identified in this review so that the molecular alterations causing drug resistance in CRC can be studied.Current literature formed the basis of this review by reviewing the molecular processes that underlie CRC, with emphasis on the mutational alterations in genes such as SENP1, KRAS, APC, TP53, and BRAF that play critical roles in CRC and resistance to treatment. Chemotherapy for CRC, targeting therapies, and immuno therapies have been discussed particularly with reference to their effectiveness for treatment and overcoming resistance.Genomic alterations in some important genes are involved in the onset of CRC and also determined the response to therapies. The KRAS mutations are associated with the resistance to EGFR inhibitors; however, BRAF mutations require BRAF/MEK inhibitors. Lack of MMR system SSR as a trigger for MSI-H status suggests a better response to immunotherapies. In addition, new molecules including SENP1, which involved the DNA repair pathway, and combination using CDK4/6 inhibitors are currently under development to overcome resistance and enhance the patients’ benefits.Colorectal cancer is still a problem, primarily because of its genetic character and high rates of recurrence. Even though chemotherapy and targeted therapies offer helpful results, the problem of resistance stands in the way. Subsequent studies should aim at symptomatic treatment outcomes and combine different drugs in order to enhance long-term treatment outcomes.

Harnessing the role of aberrant cell signaling pathways in glioblastoma multiforme: a prospect towards the targeted therapy.

Glioblastoma Multiforme (GBM), designated as grade IV by the World Health Organization, is the most aggressive and challenging brain tumor within the central nervous system. Around 80% of GBM patients have a poor prognosis, with a median survival of 12-15months. Approximately 90% of GBM cases originate from normal glial cells via oncogenic processes, while the remainder arise from low-grade tumors. GBM is notorious for its heterogeneity, high recurrence rates, invasiveness, and aggressive behavior. Its malignancy is driven by increased invasive migration, proliferation, angiogenesis, and reduced apoptosis. Throughout various stages of central nervous system (CNS) development, pivotal signaling pathways, including Wnt/β-catenin, Sonic hedgehog signaling (Shh), PI3K/AKT/mTOR, Ras/Raf/MAPK/ERK, STAT3, NF-КB, TGF-β, and Notch signaling, orchestrate the growth, proliferation, differentiation, and migration of neural progenitor cells in the brain. Numerous upstream and downstream regulators within these signaling pathways have been identified as significant contributors to the development of human malignancies. Disruptions or aberrant activations in these pathways are linked to gliomagenesis, enhancing the invasiveness, progression, and aggressiveness of GBM, along with epithelial to mesenchymal transition (EMT) and the presence of glioma stem cells (GSCs). Traditional GBM treatment involves surgery, radiotherapy, and chemotherapy with Temozolomide (TMZ). However, most patients experience tumor recurrence, leading to low survival rates. This review provides an overview of the major cell signaling pathways involved in gliomagenesis. Furthermore, we explore the signaling pathways leading to therapy resistance and target key molecules within these signaling pathways, paving the way for the development of novel therapeutic approaches.

Outcomes of the effect of exercise on cognitive function in patients with depression: A meta-analysis.

Major depressive disorder is a common mental disorder, characterized by a high rate of suicide and recurrence, which is frequently accompanied by cognitive impairments, particularly in executive function, memory, attention, and information processing speed. As such, improving the cognitive function in patients with depression and enhancing their quality of life are urgent issues. To perform a systematic review and meta-analysis of the effects of exercise on cognitive function in patients with depression. The PubMed, Web of Science, Cochrane Library, Embase, China National Knowledge Infrastructure, Wanfang Medical, VIP, and Biomedical Databases for randomized controlled trials (RCTs) databases were searched (from inception to October 19, 2023) for studies investigating improvements in cognitive function in patients with depression through exercise. Tools recommended by the Cochrane Handbook for RCT evaluation, and GRADEpro and Stata17 software, were employed for risk of bias assessment, evidence grading, forest plot construction, subgroup and sensitivity analyses, and assessment of publication bias. Seventeen RCTs (1173 patients with depression) were included. Exercise had a small but significant positive effect on attention, with an effect size of 0.21, 95%CI: 0.07-0.34, P < 0.01. Specifically, aerobic exercise regimens of 30-60 minute/session, thrice a week, at moderate intensity, and sustained over 3-12 weeks, were associated with the most pronounced benefits (P < 0.05), with effect sizes for executive function, memory, and information processing speed of 0.11, 95%CI: -0.11-0.32, P = 0.34; 0.08, 95%CI: 0.00-0.16, P = 0.05; and 0.14, 95%CI: 0.04-0.25, P = 0.01, respectively. The evidence levels for attention, information processing speed, and memory were rated as 'low,' whereas that for executive function was rated as 'very low'. Exercise could improve attention and information-processing speed in patients with depression, although improvements in executive function and memory are not significant.

Combined machine learning models, docking analysis, ADMET studies and molecular dynamics simulations for the design of novel FAK inhibitors against glioblastoma

Gliomas, particularly glioblastoma (GBM), are highly aggressive brain tumors with poor prognosis and high recurrence rates. This underscores the urgent need for novel therapeutic approaches. One promising target is Focal adhesion kinase (FAK), a key regulator of tumor progression currently in clinical trials for glioma treatment. Drug development, however, is both challenging and costly, necessitating efficient strategies. Computer-Aided Drug Design (CADD), especially when combined with machine learning (ML), streamlines the processes of virtual screening and optimization, significantly enhancing the efficiency and accuracy of drug discovery. Our study integrates ML, docking analysis, ADMET (absorption, distribution, metabolism, elimination, and toxicity) studies to identify novel FAK inhibitors specific to GBM. Predictive models showed strong performance, with an R2 of 0.892, MAE of 0.331, and RMSE of 0.467 using protein-level IC50 data in combined CDK, CDK extended fingerprints, and substructure fingerprint counts derived from 1280 FAK inhibitors. Another model, based on IC50 data from 2608 compounds tested on U87-MG cells, achieved an R2 of 0.789, MAE of 0.395, and RMSE of 0.536. Using these models, we efficiently identified 275 potentially active compounds out of 5107 candidates. Subsequent ADMET analysis narrowed this down to 16 potential FAK inhibitors that meet the established drug-likeness criteria. Moreover, molecular dynamics (MD) simulations validated the stable binding interactions between the selected compounds and the FAK protein. This study highlights the effectiveness of combining ML, docking analysis, and ADMET studies to rapidly identify potential FAK inhibitors from large databases, providing valuable insights for the systematic design of FAK inhibitors.

Mediation Effects of Self-Care Self-Efficacy and Health-Promoting Behaviors on Fear of Cancer Recurrence and Posttraumatic Growth in Postoperative Patients with Cervical Cancer: A Cross-Sectional Study

PurposeThe high recurrence risks significantly contribute to poor health outcomes among postoperative cervical cancer patients. This study aimed to determine the impact of fear of cancer recurrence (FCR) on the posttraumatic growth (PTG) in postoperative cervical cancer patients and to investigate the medicating effects of self-care self-efficacy and health-promoting behaviors within this relationship. MethodsA total of 334 cervical cancer patients who undergone surgery in three tertiary hospitals in Liaoning Province, China, were recruited using a convenience sampling method. Data were collected using the general information questionnaire, the Fear of Progression Questionnaire (fear of cancer recurrence), the Post-traumatic Growth Inventory (PTG), the Strategies Used by People to Promote Health (self-care self-efficacy), and the Health-Promoting Lifestyle Profile (health-promoting behaviors). Data analysis was performed using descriptive analysis, Pearson correlations, and multiple linear regression analysis. A structural equation model was conducted using Amos 24.0 software. ResultsPTG of cervical cancer patients after surgery was significantly and negatively associated with fear of cancer recurrence (r = -.54, P < .001), while positively correlated with self-care self-efficacy (r = .51, P < .001) and health-promoting behaviors (r = .59, P < .001). The mediation model revealed that self-care self-efficacy (Boots 95% CI [-0.39, -0.15]) and health-promoting behaviors (Boots 95% CI: [-0.51, -0.24]) independently served as mediating factors, respectively. Self-care self-efficacy and health-promoting behaviors played a significant chain mediating effect between fear of cancer recurrence and PTG (Boots CI: [-0.19, -0.07]), with an indirect effect of 11.6%. ConclusionsThis study demonstrated that self-care self-efficacy and health-promoting behaviors partially mediated the relationship between fear of cancer recurrence and PTG in cervical cancer survivors after surgery. Implementing tailored interventions focused on enhancing self-care self-efficacy and health-promoting behaviors among cervical cancer survivors may help alleviate concerns about cervical cancer recurrence and enhance PTG following surgery.

Blood Extracellular Vesicles Beyond Circulating Tumour Cells: A Valuable Risk Stratification Biomarker in High-Risk Non-Muscle-Invasive Bladder Cancer Patients.

Non-muscle-invasive bladder cancer (NMIBC) prognosis varies significantly due to the biological and clinical heterogeneity. High-risk stage T1-G3, comprising 15-20% of NMIBCs, involves the lamina propria and is associated with higher rates of recurrence, progression, and cancer-specific mortality. In the present study, we have evaluated the enumeration of tumour-derived extracellular vesicles (tdEVs) and circulating tumour cells (CTCs) in high-risk NMIBC patients and their correlation with survival outcomes such as time to progression (TTP), and cancer-specific survival (CSS). Eighty-three high-risk T1-G3 NMIBC patients treated between September 2010 and January 2013 were included. Blood samples were collected before a transurethral resection of the bladder (TURB) and analysed using the CellSearch® system. The presence of at least one CTC was associated with a shorter TTP and CSS. Extending follow-up to 120 months and incorporating automated tdEV evaluation using ACCEPT software demonstrated that tdEV count may additionally stratify patient risk. Combining tdEVs and CTCs improves risk stratification for NMIBC progression, suggesting that tdEVs could be valuable biomarkers for prognosis and disease monitoring. Further research is needed to confirm these findings and establish the clinical significance of tdEVs in early-stage cancers.

Unprecedented presentation of pelvic synovial sarcoma: A compelling case report

Synovial sarcoma (SS) is a rare tumor that typically arises in various body regions, with its manifestation in the abdominal-pelvic area being exceptionally uncommon. However, despite its rarity in this location, it often metastasizes to the thorax. Despite its slow growth, it can be misdiagnosed as benign in less than 10% of cases. Diagnosis necessitates identification of the SYT-SSX fusion transcript, alongside immunohistochemical and cytogenetic assessments. Treatment involves surgical resection followed by radiotherapy for localized tumors, while chemotherapy is necessary for metastatic cases. Despite treatment, synovial sarcomas have a high recurrence rate, with about half recurring within two years. We report the case of a 73-year-old patient from sub-Saharan Africa who presented to the emergency room with obstructive symptoms, revealing a mass near the anus compressing the rectum upon imaging, causing an obstructive syndrome. Despite initial tumor resection, histological analysis identified a neurofibromatous origin. Twenty months later, recurrence prompted a hospital visit, revealing thoracic metastases necessitating surgery and chemotherapy. Subsequent analysis confirmed perianal synovial sarcoma. This case underscores the rarity of pelvic-anal synovial sarcoma and emphasizes the importance of early detection and proper management. Synovial sarcoma should figure prominently on the list of differential diagnoses of high-grade pelvic masses due to the importance of adjuvant chemotherapy.

Efficacy of Microneedle as an Assisted Therapy for Melasma: A Meta-analysis and Systematic Review of Randomized Controlled Trials.

Melasma is a common hyperpigmentary disorder, it has variety of treatment options, but it usually has a poor curative effect and high recurrence rate. Microneedles have shown certain prospects in the treatment of melasma as an assisted therapy, but there is no consensus on its efficacy and safety. To evaluate the efficacy and safety of microneedles as an adjuvant treatment for melasma. Statistical tools were used to adjust the improvement of MASI scores in all studies to obtain standardized mean differences (SMD), and then, meta-analysis were performed. Risk ratio (RR) was utilized to assess adverse reactions, clinical effectiveness, and patient satisfaction. The effects of microneedle-assisted treatment for melasma begin to manifest at the 4th week, with optimal results observed at the 24th week, and with a high patient satisfaction. Compared with oral medication alone, microneedle-assisted therapy began to be more effective at week 12 and continued by 24weeks. Compared with laser therapy alone, microneedle-assisted therapy also showed stronger efficacy, at the 8th week, microneedle-assisted treatment was significantly more effective, reaching its peak at the 12th week. Finally, in the comparison of microneedle and microinjection therapy, microneedle has always been more significant than micro-injection. Microneedle is a valuable adjunctive therapy for melasma treatment. It enhances long-term clinical outcomes compared to monotherapy and is associated with high patient satisfaction. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Targeting the Galectin-1/Ras Interaction for Treating Malignant Peripheral Nerve Sheath Tumors.

Background: Neurofibromatosis type 1 (NF1) is a common inherited neurological disorder that can lead to the development of malignant peripheral nerve sheath tumors (MPNSTs), a highly aggressive form of sarcoma. Current treatment options for MPNSTs are limited, with poor prognosis and high recurrence rates. This study aims to explore the potential of targeting the Galectin-1 (Gal-1) and Ras interaction as a novel therapeutic strategy for MPNSTs. Methods: Molecular docking simulations were conducted to identify specific residues involved in the Gal-1 and H-Ras(G12V) interaction. LLS30, a compound designed to target the Ras binding pocket on Gal-1, was developed and tested. The efficacy of LLS30 was evaluated through in vitro assays, including cell viability, apoptosis, and co-immunoprecipitation studies, as well as in vivo assays using orthotopic MPNST xenograft and experimental lung metastasis models. Transcriptome sequencing was performed to analyze the impact of LLS30 on gene expression and signaling pathways. Results: Molecular docking revealed key residues involved in the Gal-1/Ras interaction, and LLS30 was shown to bind to these residues, disrupting the interaction. LLS30 treatment resulted in Ras delocalization from the plasma membrane and suppression of the Ras/Erk signaling pathway. In vitro, LLS30 significantly reduced MPNST cell proliferation and induced apoptosis. In vivo, LLS30 demonstrated potent anti-tumor activity, reducing tumor burden and metastasis while improving survival in animal models. Transcriptome analysis showed that LLS30 downregulates critical pathways, including KRAS signaling and epithelial-mesenchymal transition (EMT). Conclusions: Interference with the Gal-1/Ras interaction could lead to suppression of the Ras signaling pathway. LLS30 effectively disrupts the Gal-1/Ras interaction, resulting in significant anti-tumor and anti-metastatic effects in MPNST models. These findings indicated that targeting Gal-1 with LLS30 offers a promising therapeutic approach for treating MPNSTs and may also be applicable to other malignancies where Gal-1 and Ras are key oncogenic drivers.

Anticoagulant Treatment May Decrease the Relapse Rate of Pulmonary Arterial Involvement in Behçet's Disease.

Pulmonary arterial involvement (PAI) is one of the most common causes of mortality in Behçet's disease (BD). In this study, we aimed to evaluate the clinical features, course, and recurrence risk factors of BD-associated PAI. BD patients who were followed up in Marmara University BD outpatient clinic between 1990 and 2023 were included. All data were acquired from the medical records of the patients. PAIs were classified according to the type of the vascular involvement as thrombosis or aneurysm. Factors affecting the risk of relapses were determined using multivariate Cox regression analysis. Among 1350 BD patients, 110 (8.1%) had PAI. The mean age (SD) of patients with PAI was 42.4 (11.6) years, and the male/female ratio was 2.2 (76/34). Thirty-two (29.1%) of 110 patients were asymptomatic. Asymptomatic patients with PAI were significantly younger (p = 0.031) than the symptomatic group. Also, a greater prevalence of females (p = 0.001) and higher recurrence rates (p = 0.019) were observed in the symptomatic group. Pulmonary arterial thrombosis was seen in 104 (94.5%) and aneurysms in 9 patients (6.6%). At least one PAI relapse was observed in 31 patients (28.2%). In multivariate analysis, the Cox regression model was significant (p = 0.013), and not starting anticoagulants independently increased the PAI relapse risk (hazards ratio, 4.36; 95% confidence interval, 1.14-24.1; p = 0.042). Pulmonary arterial thrombosis is the main presentation type of PAI in BD, whereas aneurysmatic formation is rare. Despite immunosuppressive treatment, relapses occur during follow-up in one third of patients with PAI. When anticoagulant therapy is added to immunosuppressive therapy, the relapse rate in BD patients with PAI is significantly reduced.

Modulation of the tumor microenvironment in non-muscle-invasive bladder cancer by OncoTherad® (MRB-CFI-1) nanoimmunotherapy: effects on tumor-associated macrophages, tumor-infiltrating lymphocytes, and monoamine oxidases.

Non-muscle-invasive bladder cancer (NMIBC) presents management challenges due to its high recurrence rate and a complex tumor microenvironment (TME). This study investigated the effects of OncoTherad® (MRB-CFI1) nanoimmunotherapy on the TME of BCG-unresponsive NMIBC, focusing on alterations in monoamine oxidases (MAO-A and MAO-B) and immune markers: CD163, FOXP3, CD8, and CX3CR1. A comparative analysis of immunoreactivities was made before and after OncoTherad® treatment and an immune score (IS) was established to evaluate the correlation between immunological changes and clinical outcomes. Forty bladder biopsies of twenty patients were divided into 2 groups (n = 20/group): 1 (pre-treatment biopsies); and 2 (post-treatment biopsies). Our results showed stable MAO-A levels but a significant (p < 0.05) decrease in MAO-B immunoreactivity after treatment, suggesting OncoTherad®'s efficacy in targeting the tumor-promoting and immunosuppressive functions of MAO-B. Significant (p < 0.05) reductions in CD163 and FOXP3 immunoreactivities were seen in post-treatment biopsies, indicating a decreased presence of M2 macrophages and Tregs. Corroborating with these results, we observed reductions in tumor histological grading, focality and size, factors that collectively enhanced recurrence-free survival (RFS) and pathological complete response (PCR). Moreover, elevated IFN-γ immunoreactivities in treated biopsies correlated with increased counts of CD8+ T cells and higher CX3CR1 expression, underscoring OncoTherad®'s enhancement of cytotoxic T cell functionality and overall antitumor immunity. The IS revealed improvements in immune responses post-treatment, with higher scores associated with better RFS and PCR outcomes. These findings validate OncoTherad®'s capability to modify the bladder cancer microenvironment favorably, promoting effective immune surveillance and response.

Impact of Sinus CT Severity Score on the Outcomes of Endoscopic Sinus Surgery in Eosinophilic CRSwNP.

Eosinophilic chronic rhinosinusitis with nasal polyps (eos-CRSwNP), especially those with diffuse disease as indicated by CT scans, has high recurrence rate and low control rate after endoscopic sinus surgery (ESS). Most of them are difficult to treat. This study sought to identify if eos-CRSwNP patients were to undergo surgery earlier, while the disease is still limited on CT, they might achieve better postoperative outcomes. This study enrolled eos-CRSwNP patients with different degree of sinus involvement who underwent primary ESS and compared the surgical outcomes of the patients exhibiting mild sinus involvement with those displaying severe sinus involvement. The demographic data, preoperative disease severity, and surgery outcomes at 1 year postoperatively were collected. CRS control status was the primary endpoint to evaluate the outcomes. This study included 118 patients with at least one-year follow-up. The overall uncontrolled rate was 33.1% at 1 year postoperatively. The best cut-off value for CT Lund-Mackay (L-M) score was 13 to predict the uncontrolled status (AUC = 0.67). Then, patients were divided into the mild group (L-M < 13, n = 70) and the severe group (L-M ≥ 13, n = 48) according to L-M score. The follow-up data indicated that 24.3% of patients (17/70) in the mild group and 45.8% of patients (22/48) in the severe group were uncontrolled (p = 0.015). Postoperative endoscopic score in the mild group was significantly better than those in the severe group (p = 0.002). ESS performed on eos-CRSwNP patients with mild sinus involvement have better postoperative outcomes at 1 year than patients with severe sinus involvement. Level 3 Laryngoscope, 2024.