High Recurrence Research Articles

470. INTENSIVE EARLY SURVEILLANCE FOLLOWING ESOPHAGECTOMY IDENTIFIES DISTINCT PATTERNS OF RECURRENCE

Abstract Background There remains a lack of consensus about the protocol for follow-up following esophagectomy. Some centers will utilize a purely radiological approach to follow-up, while others will include routine endoscopy and blood markers. Furthermore, the frequency of follow-up is debated, though many centers will follow-up every 3 months due to the high recurrence rate in the first year. We follow patients every 3 months for the first year, every 6 months for the next year, then yearly to 5 years, solely with CT scans unless symptoms indicate endoscopy. We sought to examine our recurrence rate and survival using this follow-up protocol. Methods We reviewed our prospectively collected database for recurrence following esophagectomy in patients operated from March 2018 to May 2022. Consenting patients >18 years of age who underwent esophagectomy were included. Demographics including age, sex, and BMI, tumor factors including pathologic stage, tumor regression grade, and neoadjuvant therapy and post-recurrence treatment data were collected. Results We identified 190 patients who underwent esophagectomy and 69 patients had a recurrence. Patients with recurrence were younger (61.3 +/- 10.2 vs 66.4 +/- 10.1, p=0.001), were more likely pT3 (59.4% vs 36.4%, p=0.013) and have a tumor regression grade of 3 (27.5% vs 7.4%, p=0.002). There was no difference between patients with R1 resections vs R0 (5.8% vs 6.6%, p=0.824). Most recurrences were identified on CT scan (95.8%). For patients who recurred within 3 months, the mean time from operation to death was 9.11 months. Patients who recurred between 3-6mo, 6-9mo, and 9-12mo died at 17.1mo, 15.7mo, and 17.5mo following surgery, respectively. Patients who recurred in the next year died around 40 months from surgery. Conclusion As with other reports in the literature, recurrence is highest in the first year after esophagectomy. Patients recurring in the first 3 months had a short survival following esophagectomy and may represent missed micrometastatic disease at staging. Interestingly, patients who recurred between 3-12 months all had a similar time to death from the date of operation, suggesting lead-time bias for those detected at 3-6months. Early and later recurrence appear to have distinct biological behaviours. With improved and tailored adjuvant therapies, earlier detection may yet be beneficial and will require further study.

Blood Flow Restriction Training Improves Muscular Outcomes in Patients With Chronic Ankle Instability: A Critically Appraised Topic

Clinical Scenario: The high recurrence of lateral ankle sprains progresses to chronic ankle instability (CAI) and can affect many athletes in all sports. CAI is often associated with a decrease in muscle strength, an increase in pain, a decrease in the range of motion, and a decrease in balance or neuromuscular control. The use of blood flow restriction (BFR) with CAI can increase muscular outcomes and be used as a rehabilitation tool. Clinical Question: Is there evidence to suggest that BFR improves strength, muscle activation, and/or cross-sectional area of the lower leg musculature in those with CAI? Clinical Bottom Line: There is moderate evidence to support therapeutic exercise with low-intensity BFR in patients with CAI. The evidence concluded a significant improvement in BFR to increase muscle activation of the fibularis longus, anterior tibialis, vastus lateralis, and soleus. There is moderate evidence suggesting BFR can induce strength gains in the muscles of the lower extremity in patients with CAI. Strength of Recommendation: The comprehensive evidence is a Strength of Recommendation Taxonomy (SORT) Grade B, with a level of evidence of 2, according to the Centre for Evidence-Based Medicine (CEBM) for the studies included.

Longitudinal multiomics analysis of aggressive pituitary neuroendocrine tumors: comparing primary and recurrent tumors from the same patient, reveals genomic stability and heterogeneous transcriptomic profiles with alterations in metabolic pathways

Pituitary neuroendocrine tumors (PitNET) represent the vast majority of sellar masses. Some behave aggressively, growing rapidly and invading surrounding tissues, with high rates of recurrence and resistance to therapy. Our aim was to establish patterns of genomic, transcriptomic and methylomic evolution throughout time in primary and recurrent tumors from the same patient. Therefore, we performed transcriptome- and exome-sequencing and methylome microarrays of aggressive, primary, and recurrent PitNET from the same patient. Primary and recurrent tumors showed a similar exome profile, potentially indicating a stable genome over time. In contrast, the transcriptome of primary and recurrent PitNET was dissimilar. Gonadotroph, silent corticotroph, as well as metastatic corticotroph and a somatotroph PitNET expressed genes related to fatty acid biosynthesis and metabolism, phosphatidylinositol signaling, glycerophospholipid and phospholipase D signaling, respectively. Diacylglycerol kinase gamma (DGKG), a key enzyme in glycerophospholipid metabolism and phosphatidylinositol signaling pathways, was differentially expressed between primary and recurrent PitNET. These alterations did not seem to be regulated by DNA methylation, but rather by several transcription factors. Molecular docking showed that dasatinib, a small molecule tyrosine kinase inhibitor used in the treatment of chronic lymphocytic and acute lymphoblastic leukemia, could target DGKG. Dasatinib induced apoptosis and decreased proliferation in GH3 cells. Our data indicate that pituitary tumorigenesis could be driven by transcriptomically heterogeneous clones, and we describe alternative pharmacological therapies for aggressive and recurrent PitNET.

Deciphering Dormant Cells of Lung Adenocarcinoma: Prognostic Insights from O-glycosylation-Related Tumor Dormancy Genes Using Machine Learning.

Lung adenocarcinoma (LUAD) poses significant challenges due to its complex biological characteristics and high recurrence rate. The high recurrence rate of LUAD is closely associated with cellular dormancy, which enhances resistance to chemotherapy and evasion of immune cell destruction. Using single-cell RNA sequencing (scRNA-seq) data from LUAD patients, we categorized the cells into two subclusters: dormant and active cells. Utilizing high-density Weighted Gene Co-expression Network Analysis (hdWGCNA) and pseudo-time cell trajectory, aberrant expression of genes involved in protein O-glycosylation was detected in dormant cells, suggesting a crucial role for O-glycosylation in maintaining the dormant state. Intercellular communication analysis highlighted the interaction between fibroblasts and dormant cells, where the Insulin-like Growth Factor (IGF) signaling pathway regulated by O-glycosylation was crucial. By employing Gene Set Variation Analysis (GSVA) and machine learning, a risk score model was developed using hub genes, which showed high accuracy in determining LUAD prognosis. The model also demonstrated robust performance on the training dataset and excellent predictive capability, providing a reliable basis for predicting patient clinical outcomes. The group with a higher risk score exhibited a propensity for adverse outcomes in the tumor microenvironment (TME) and tumor mutational burden (TMB). Additionally, the 50% inhibitory concentration (IC50) values for chemotherapy exhibited significant variations among the different risk groups. In vitro experiments demonstrated that EFNB2, PTTG1IP, and TNFRSF11A were upregulated in dormant tumor cells, which also contributed greatly to the diagnosis of LUAD. In conclusion, this study highlighted the crucial role of O-glycosylation in the dormancy state of LUAD tumors and developed a predictive model for the prognosis of LUAD patients.

Establishment and characterization of two novel patient-derived cell lines from myxofibrosarcoma: NCC-MFS7-C1 and NCC-MFS8-C1.

Myxofibrosarcoma (MFS), an aggressive soft tissue sarcoma, presents a significant challenge because of its high recurrence rate, distal metastasis, and complex genetic background. Although surgical resection is the standard treatment for MFS, the outcomes are unsatisfactory and effective non-surgical treatment strategies, including drug therapy, are urgently warranted. MFS is a rare tumor that requires comprehensive preclinical research to develop promising drug therapies; however, only two MFS cell lines are publicly available worldwide. The present study reports two novel patient-derived MFS cell lines, NCC-MFS7-C1 and NCC-MFS8-C1. These cell lines have been extensively characterized for their genetic profile, proliferation, spheroid-forming capacity, and invasive behavior, confirming that they retain MFS hallmarks. Furthermore, we conducted comprehensive drug screening against these cell lines and six others previously established in our laboratory to identify potential therapeutic candidates for MFS. Among the screened agents, actinomycin D, bortezomib, and romidepsin demonstrated considerable antiproliferative effects that were superior to those of doxorubicin, a standard drug, highlighting their potential as novel drugs. In conclusion, NCC-MFS7-C1 and NCC-MFS8-C1 are valuable research resources that contribute to the understanding of the pathogenesis and development of novel therapies for MFS.

De Quervain Tendinopathy: Anatomical Prognostic Indicators of Corticosteroid Injection Success

Background: Anatomical variations of the first extensor compartment can affect de Quervain tendinopathy outcomes. Our study aimed to identify the anatomical prognostic indicators of symptom recurrence following a corticosteroid (CS) injection and to assess the efficacy of CS injections. Methods: Fifty consecutive patients received a single CS injection for de Quervain tendinopathy. Ultrasound imaging was used to assess anatomical factors of the first extensor tendon compartment of the wrist. The primary outcome was recurrence after six weeks and six months and the identification of the anatomical prognostic indicators of the recurrence. The Disabilities of the Arm, Shoulder, and Hand (DASH) score and the Visual Analogue Scale (VAS) for pain were evaluated as secondary outcomes. Results: Fifteen patients (30%) experienced symptom recurrence within six weeks. The intracompartmental septum and the number of tendon slips were associated with higher recurrence rates (adjusted odds ratio for the septum: 18.39, p = 0.045; adjusted odds ratio for each additional tendon slip: 24.68, p < 0.01). The mean DASH score improved from 74.1 ± 5 to 19.3 ± 25.3, and the mean VAS for pain from 8.5 ± 0.8 to 2 ± 2.7 (p < 0.01 for both scores). Five patients experienced minor adverse events with spontaneous improvement. Conclusions: CS injections are a viable treatment for de Quervain tendinopathy. Anatomical variations can predict treatment success. Counseling patients based on these factors can help guide treatment decisions, including surgical options.

Multimodal ischemic stroke recurrence prediction model based on the capsule neural network and support vector machine.

Ischemic stroke (IS) has a high recurrence rate. Machine learning (ML) models have been developed based on single-modal biochemical tests, and imaging data have been used to predict stroke recurrence. However, the prediction accuracy of these models is not sufficiently high. Therefore, this study aimed to collect biochemical detection and magnetic resonance imaging (MRI) data to establish a dataset and propose a high-performance heterogeneous multimodal IS recurrence prediction model based on deep learning. This is a retrospective cohort study. Data were retrospectively collected from 634 IS patients in Zhuhai, China, a 12-month follow-up was conducted to determine stroke recurrence. We propose the ischemic stroke multi-group learning (ISGL) model, an integrated model for predicting the recurrence risk of multimodal IS in patients, based on a capsule neural network and a linear support vector machine (SVM). Two capsule neural network prediction models based on T1 and T2 signals in the MRI data and a SVM prediction model based on biochemical test data were established. Finally, a vote was conducted on the final judgment of the integrated model. The ISGL model was compared with 6 classical ML and deep learning models: k-nearest neighbors, SVM, logistic regression, random forest, eXtreme Gradient Boosting, and visual geometry group. The results revealed that the accuracy, specificity, sensitivity and the area under the curve of the ISGL model were 95%, 96%, 94%, and 95%, respectively. Among the comparison models, the visual geometry group method exhibited the best performance, but it much lower than those of the ISGL model. Analysis of the importance of biochemical test data revealed that low-density lipoprotein, smoking, and heart disease history were the positively correlated factors, and total cholesterol, high-density lipoprotein, and diabetes were and the negatively correlated factors. This study proposes the ISGL model can be used simultaneously with MRI and biochemical data to predict IS recurrence. This combination resulted in higher rate of performance than that of the other ML models. Additionally, this study found related risk factors affected recurrence, which can be used to intervene in high-risk patients' recurrence as early as possible and promote the development of secondary prevention of stroke.

Recent Advances in Drug Delivery Strategies for High-Risk BCG-Unresponsive Non-Muscle Invasive Bladder Cancer: A Brief Review from 2018 to 2024

High-risk BCG-unresponsive non-muscle invasive bladder cancer (NMIBC) is a condition that is typically treated with Bacillus Calmette–Guérin (BCG) therapy. Unfortunately, NMIBC is characterized by high recurrence, with a significant percentage of BCG patients ultimately requiring radical cystectomy. As a consequence, the development of effective new therapies to avoid RC has become a rapidly evolving field to address this unmet clinical need. To date, three biologics—Keytruda, Adstiladrin, and Anktiva—have been approved by the FDA, and multiple drug modalities, particularly gene therapies, have shown promising results in clinical trials. Advances in drug delivery strategies, such as targeted delivery, sustained release, and permeabilization of protective layers, are critical in overcoming the challenges posed by therapeutic intervention in bladder cancer. This review focuses on high-risk BCG-unresponsive NMIBC therapies that have been or are currently being investigated in clinical trials, offering a broad overview of the delivery system designs and up-to-date clinical outcomes that have been reported as of July 2024. It aims to inform the development of future drug delivery systems for second-line therapies in high-risk BCG-unresponsive NMIBC.

A dendritic cell-recruiting, antimicrobial blood clot hydrogel for melanoma recurrence prevention and infected wound management

Surgical resection, the mainstay for melanoma treatment, faces challenges due to high tumor recurrence rates and complex postoperative wound healing. Chronic inflammation from residual disease and the risk of secondary infections impede healing. We introduce an innovative, injectable hydrogel system that integrates a multifaceted therapeutic approach. The hydrogel, crosslinked by calcium ions with sodium alginate, encapsulates a blood clot rich in dendritic cells (DCs) chemoattractants and melanoma cell-derived nanovesicles (NVs), functioning as a potent immunostimulant. This in situ recruitment strategy overcomes the limitations of subcutaneous tumor vaccine injections and more effectively achieves antitumor immunity. Additionally, the hydrogel incorporates Chlorella extracts, enhancing its antimicrobial properties to prevent wound infections and promote healing. One of the key findings of our research is the dual functionality of Chlorella extracts; they not only expedite the healing process of infected wounds but also increase the hydrogel's ability to stimulate an antitumor immune response. Given the patient-specific nature of the blood clot and NVs, our hydrogel system offers customizable solutions for individual postoperative requirements. This personalized approach is highlighted by our study, which demonstrates the synergistic impact of the composite hydrogel on preventing melanoma recurrence and hastening wound healing, potentially transforming postsurgical melanoma management.

A Study on the Effect of Manual Therapy on Physical Function Improvement in Middle-Aged Women with Lumbago

Most people experience lumbago at least once in their lifetime. In particular, it was found that lumbago prevalence was high in women experiencing pregnancy and childbirth. However, lumbago is difficult to be cured and has a high recurrence rate. This study, accordingly, investigated the effects of easily-accessible manual therapy on lumbago and physical function in middle-aged women. Subjects were randomly assigned to an experimental group to receive manual therapy and a control group to receive hyperthermia, and the Oswestry Disability Index (ODI) and joint range of motion were measured and analyzed. The results showed a positive effect on physical function improvement and back pain reduction in the experimental group to which manual therapy was applied, supporting that manual therapy is an alternative therapy that can help reduce lumbago and improve physical function in middle-aged women.

Signaling molecules in the microenvironment of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a major fatal cancer that is known for its high recurrence and metastasis. An increasing number of studies have shown that the tumor microenvironment is closely related to the metastasis and invasion of HCC. The HCC microenvironment is a complex integrated system composed of cellular components, the extracellular matrix (ECM), and signaling molecules such as chemokines, growth factors, and cytokines, which are generally regarded as crucial molecules that regulate a series of important processes, such as the migration and invasion of HCC cells. Considering the crucial role of signaling molecules, this review aims to elucidate the regulatory effects of chemokines, growth factors, and cytokines on HCC cells in their microenvironment to provide important references for clarifying the development of HCC and exploring effective therapeutic targets.

Elevated nuclear expression of ZHX1 correlates with poor prognosis in hepatocellular carcinoma (HCC): Comparison of nuclear and cytoplasmic distribution of the ZHX family in HCC cells.

The role of the zinc fingers and homeoboxes family (ZHX1-3), transcriptional repressors, through their subcellular localization in hepatocellular carcinoma (HCC), is not fully understood. The present study aimed to examine the differential nuclear and cytoplasmic expression of ZHXs in HCC tissues. Immunohistochemistry was utilized to detect the expression of ZHXs in 54 liver tissues from HCC (n=33), hepatitis C (n=16), and the normal liver tissue surrounding hepatic metastasis of colorectal cancer (n=5). Next-generation sequencing and digital polymerase chain reaction identified gene mutations associated with HCC. Kaplan-Meier curves were constructed to evaluate the relationship between ZHX expression and survival. The results were validated using data from The Cancer Genome Atlas. Univariate and multivariate Cox regression analyses were undertaken to identify independent prognostic factors. High nuclear expression of ZHX1 was associated with poor overall survival (OS), while high nuclear expression of ZHX2 correlated with higher recurrence. Conversely, patients with high cytoplasmic expression of ZHX3 had lower recurrence and better OS. Hepatitis B virus-associated HCC was related to high cytoplasmic expression of ZHX1, which was marginally related to telomerase reverse transcriptase (TERT) promoter mutation-negative HCC. In contrast, low nuclear expression of ZHX3 was associated with TERT promoter mutation-positive HCC and HCC patients over 70years old. These results suggest that the expression and localization of different ZHXs may be related to HCC progression, potentially inferring genetic backgrounds such as TERT promoter mutation. Further studies on the relationship between HCC and ZHXs will enhance our understanding and control of HCC.

Unraveling the Role of Bromodomain and Extra-Terminal Proteins in Human Uterine Leiomyosarcoma.

Uterine leiomyosarcoma (uLMS) is the most common type of uterine sarcoma, associated with poor prognosis, high rates of recurrence, and metastasis. Currently, the molecular mechanism of the origin and development of uLMS is limited. Bromodomain and extra-terminal (BET) proteins are involved in both physiological and pathological events. However, the role of BET proteins in the pathogenesis of uLMS is unknown. Here, we show for the first time that BET protein family members, BRD2, BRD3, and BRD4, are aberrantly overexpressed in uLMS tissues compared to the myometrium, with a significant change by histochemical scoring assessment. Furthermore, inhibiting BET proteins with their small, potent inhibitors (JQ1 and I-BET 762) significantly inhibited the uLMS proliferation dose-dependently via cell cycle arrest. Notably, RNA-sequencing analysis revealed that the inhibition of BET proteins with JQ1 and I-BET 762 altered several critical pathways, including the hedgehog pathway, EMT, and transcription factor-driven pathways in uLMS. In addition, the targeted inhibition of BET proteins altered several other epigenetic regulators, including DNA methylases, histone modification, and m6A regulators. The connections between BET proteins and crucial biological pathways provide a fundamental structure to better understand uterine diseases, particularly uLMS pathogenesis. Accordingly, targeting the vulnerable epigenome may provide an additional regulatory mechanism for uterine cancer treatment.

Patient-derived ovarian cancer organoid carries immune microenvironment and blood vessel keeping high response to cisplatin.

Ovarian cancer is high recurrence and mortality malignant tumor. The most common ovarian cancer was High-Grade Serous Ovarian Cancer. However, High-Grade Serous Ovarian Cancer organoid is rare, which organoid with patient immune microenvironment and blood vessels even absence. Here, we report a novel High-Grade Serous Ovarian Cancer organoid system derived from patient ovarian cancer samples. These organoids recapitulate High-Grade Serous Ovarian Cancer organoids' histological and molecular heterogeneity while preserving the critical immune microenvironment and blood vessels, as evidenced by the presence of CD34 + endothelial cells. Whole exome sequencing identifies key mutations (CSMD3, TP53, GABRA6). Organoids show promise in testing cisplatin sensitivity for patients resistant to carboplatin and paclitaxel, with notable responses in cancer proteoglycans and p53 (TP53) signaling, like ACTG/ACTB1/AKT2 genes and BBC3/MDM2/PERP. Integration of immune microenvironment and blood vessels enhances potential for novel therapies like immunotherapies and angiogenesis inhibitors. Our work may provide a new detection system and theoretical basis for ovarian cancer research and individual therapy.

A Case of Nasoseptal Flap Reconstruction for Refractory Medial Canthal Fistula.

Sino-orbital cutaneous fistulas (SOCFs) are a rare and challenging complication from conditions including granulomatosis with polyangiitis. SOCFs are difficult to manage due to poor vascular supply, compromised tissue, and systemic immunocompromise, which lead to a high rate of recurrence. Given the overall rarity of SOCFs, optimal surgical repair remains controversial, with options ranging from conservative management, onlay grafts, and vascularized flaps. This case report describes a novel one-step approach to SOCF closure using a composite chondral mucosal nasoseptal flap in a patient with a large left medial canthal SOCF that had recurred despite 2 prior attempts at closure including a vascularized paramedian forehead flap. Nasoseptal flaps may provide vascularized mucosal tissue to allow for greater success in closure over traditional, external flaps, and skin grafts.

Oncofetal IGF2BP3-mediated control of microRNA structural diversity in the malignancy of early-stage lung adenocarcinoma

The nature of microRNA (miRNA) dysfunction in carcinogenesis remains controversial because of the complex connection between miRNA structural diversity and biological processes. Here, we found that oncofetal IGF2BP3 regulates the selective production of a subset of 3'-isoforms (3'-isomiRs), including miR-21-5p and Let-7 family, which induces significant changes in their cellular seed occupancy and structural components, establishing a cancer-specific gene expression profile. The D-score, reflecting dominant production of a representative miR-21-5p+C (a 3'-isomiR), discriminated between clinical early-stage lung adenocarcinoma (LUAD) cases with low and high recurrence risks, and was associated with molecular features of cell cycle progression, epithelial-mesenchymal transition pressure, and immune evasion. We found that IGF2BP3 controls the production of miR-21-5p+C by directing the nuclear Drosha complex to select the cleavage site. IGF2BP3 was also involved in the production of 3'-isomiRs of miR-425-5p and miR-454-3p. IGF2BP3-regulated these three miRNAs are suggested to be associated with the regulation of p53, TGF-β, and TNF pathways in LUAD. Knockdown of IGF2BP3 also induced a selective upregulation of Let-7 3'-isomiRs, leading to increased cellular Let-7 seed occupancy and broad repression of its target genes encoding cell cycle regulators. The D-score is an index that reflects this cellular situation. Our results suggest that the aberrant regulation of miRNA structural diversity is a critical component for controlling cellular networks, thus supporting the establishment of a malignant gene expression profile in early stage LUAD.

Impact of self-expanding metal stents on long-term survival outcomes as a bridge to surgery in patients with colon cancer obstruction: Current state and future prospects.

Since self-expanding metal stents (SEMS) were first introduced in acute colon cancer obstruction, the increased rate of primary anastomosis and improved quality of life following SEMS placement have been clearly shown. However, it was demonstrated that SEMS are associated with higher recurrence rates. Although several trials have shown that overall and disease-free survival in patients following SEMS placement is similar with patients undergoing emergency surgery, obstruction and a high incidence of recurrence imposed many concerns. The optimal time interval from SEMS to surgery is still a matter of debate. Some studies have recommended a time interval of ~2 weeks between SEMS insertion and elective surgery. A prolonged interval of time from SEMS insertion to elective surgery and the administration of neoadjuvant chemotherapy (NAC) has been proposed. SEMS-NAC might have advantages for improving the surgical and long-term survival outcomes of patients with acute colon cancer obstruction, which is an optional approach in the management of acute colon cancer obstruction.

Ginsenoside Re Prevents Depression-like Behaviors via Inhibition of Inflammation, Oxidative Stress, and Activating BDNF/TrkB/ERK/CREB Signaling: An In Vivo and In Vitro Study.

Depression is a widespread disease, with high mortality and recurrence rates. Recent studies have shown that elevated cytokine levels are implicated in the molecular mechanisms of depression. Oxidative stress contributes to the stimulation of cytokine production. Growing evidence suggests that ginsenoside Re (Gs-Re) exerts a neuroprotective effect on the hippocampus by suppressing oxidative stress and inflammation. However, the effect and mechanism of Gs-Re in the treatment of depression remain understudied. This study aimed to evaluate the neuroprotective and antidepressant-like effects of Gs-Re and the possible underlying mechanisms. In this article, the antidepressant-like effect of the Gs-Re was studied both in vitro (H2O2-induced oxidative stress in HT-22 cells) and in vivo (reserpine-induced depressive model mice). Our results indicated that, at the cellular level, Gs-Re effectively enhanced cell survival following H2O2 stimulation, inhibited the mass production of oxidative stress markers (MDA and ROS), and prevented the occurrence of apoptosis. Moreover, Gs-Re significantly reduced the levels of proinflammatory cytokines IL-1β, IL-6, and TNF-α and restored the abnormal mitochondrial membrane potential. Subsequently, Gs-Re treatment reversed reserpine-induced neuroinflammation and depressive-like behaviors in vivo and inhibited microglia overactivation. Furthermore, the alterations in the BDNF/TrkB/ERK/CREB signaling pathway induced by H2O2 or reserpine in HT-22 cells or in the mouse hippocampus were significantly reversed by Gs-Re. K252a blocked the improvement of Gs-Re on depression-like behavior and eliminated the inhibition of oxidative stress and neuroinflammation in vivo. This study suggested that Gs-Re produces neuroprotective and depressive effects by inhibiting oxidative stress and inflammation and activating the BDNF/TrkB/ERK/CREB pathway.

Decitabine-based treatment strategy improved the outcome of HSCT in JMML: a retrospective cohort study.

Pre-HSCT disease control, suboptimal long-term prognosis, and a high recurrence incidence (RI) continue to pose significant challenges for hematopoietic stem cell transplantation (HSCT) in juvenile myelomonocytic leukemia (JMML) patients. This retrospective cohort study assessed the effectiveness of a decitabine (DAC)-based protocol in JMML patients undergoing HSCT. The pre-HSCT treatment includes initial and bridging treatment. The efficacy of DAC monotherapy versus DAC combined with cytotoxic chemotherapy(C-DAC) as initial treatment was compared, followed by DAC plus FLAG (fludarabine, cytarabine, and GCSF) as bridging treatment. The HSCT regimens were based on DAC, fludarabine, and busulfan. Post-HSCT, low-dose DAC was used as maintenance therapy. The study endpoints focused on pretransplantation simplified clinical response and post-HSCT survival. There were 109 patients, including 45 receiving DAC monotherapy and 64 undergoing C-DAC treatment. 106 patients completed bridging treatment. All patients were administered planned HSCT regimens and post-HSCT treatment. The initial treatment resulted in 88.1% of patients achieving clinical remission without a significant difference between the DAC and C-DAC groups (p=0.769). Clinical remission rates significantly improved following bridging treatment (p=0.019). The 5-year overall survival, leukemia-free survival, and RI were 92.2%, 88.4%, and 8.0%, respectively. A poor clinical response to pre-HSCT treatment emerged as a risk factor for OS (hazard ratio: 9.8, 95% CI: 2.3-41.1, p=0.002). Implementing a DAC-based administration strategy throughout the pre-HSCT period, during HSCT regimens, and in post-HSCT maintenance significantly reduced relapse and improved survival in JMML patients. Both DAC monotherapy and the DAC plus FLAG protocol proved effective as pre-HSCT treatments.

Performance of different CT enhancement quantification methods as predictors of pancreatic cancer recurrence after upfront surgery

The prognosis of pancreatic cancer (PDAC) after tumor resection remains poor, mostly due to a high but variable risk of recurrence. A promising tool for improved prognostication is the quantification of CT tumor enhancement. For this, various enhancement formulas have been used in previous studies. However, a systematic comparison of these formulas is lacking. In the present study, we applied twenty-three previously published CT enhancement formulas to our cohort of 92 PDAC patients who underwent upfront surgery. We identified seven formulas that could reliably predict tumor recurrence. Using these formulas, weak tumor enhancement was associated with tumor recurrence at one and two years after surgery (p ≤ 0.030). Enhancement was inversely associated with adverse clinicopathological features. Low enhancement values were predictive of a high recurrence risk (Hazard Ratio ≥ 1.659, p ≤ 0.028, Cox regression) and a short time to recurrence (TTR) (p ≤ 0.027, log-rank test). Some formulas were independent predictors of TTR in multivariate models. Strikingly, almost all of the best-performing formulas measure solely tumor tissue, suggesting that normalization to non-tumor structures might be unnecessary. Among the top performers were also the absolute arterial/portal venous tumor attenuation values. These can be easily implemented in clinical practice for better recurrence prediction, thus potentially improving patient management.