Method to Study the Survival Abilities of Foodborne Bacterial Pathogens Under Food Processing Conditions.

Properly using controllable atmospheric containers can facilitate investigations of the survival abilities and physiological states of key and emerging-foodborne pathogens under recreated applicable food processing environmental conditions. Notably, saturated salt solutions can efficiently control relative humidity in airtight containers. This chapter describes a practical experimental setup, with necessary prerequisites for exposing foodborne pathogens to simulated and relevant food processing environmental conditions. Subsequent analyses for studying cell physiology will also be suggested.

Encapsulation of Lactiplantibacillus plantarum with casein-gellan gum emulsions to enhance its storage, pasteurization, and gastrointestinal survival.

Probiotics serve a very important role in human health. However, probiotics have poor stability during processing, storage, and gastrointestinal digestion. The gellan gum (GG) is less susceptible to enzymatic degradation and resistant to thermal and acidic environments. This study investigated the effect of casein (CS)-GG emulsions to encapsulate Lactiplantibacillus plantarum CICC 6002 (L. plantarum CICC 6002) on its storage stability, thermal stability, and gastrointestinal digestion. L. plantarum CICC 6002 was suspended in palm oil and emulsions were prepared using CS or CS-GG complexes. We found the CS-GG emulsions improved the viability of L. plantarum CICC 6002 after storage, pasteurization, and digestion compared to the CS emulsions. In addition, we investigated the influence of the gellan gum concentration on emulsion stability, and the optimal stability was observed in the emulsion prepared by CS-0.8% GG complex. This study provided a new strategy for the protection of probiotics based on CS-GG delivery system.

MiRNA expression affects survival in patients with obstructive sleep apnea and metastatic colorectal cancer.

Introduction: The relationship between obstructive sleep apnea (OSA) and cancer has been recognized for some time now. However, little is known about the mechanisms by which sleep apnea promotes tumorigenesis and the impact of OSA on survival after cancer diagnosis. In the last few years, research has focused on the exploration of different biomarkers to understand the mechanisms underlying this relationship and miRNAs, non-coding single strands of about 22 nucleotides that post-transcriptionally regulate gene expression, have emerged as possible actors of this process.The aim of the study was to evaluate the impact of OSA on survival of metastatic colorectal cancer (mCRC) patients based on the expression of specific miRNAs. Methods: The expression of 6 miRNAs, respectively miR-21, miR-23b, miR-26a, miR-27b, miR-145 and miR-210, was analyzed by qRT-PCR in patients' sera. Response to first-line therapy, Kaplan-Meier curves of overall and progression-free survival were used to evaluate survival in mCRC patients with and without OSA stratified for the expression of miRNAs. Results: The expression of miR-21, miR-23b, miR-26a and miR-210 was significantly upregulated in mCRCs with OSA compared to no OSA. In mCRC patients with OSA and increasing expression of miR-21, miR-23b, miR-26a and miR-210 risk of progression after first-line therapy was higher and both overall and progression-free survival were significantly worst. Conversely, as miR-27b and miR-145 expression increased, the life expectancy of patients diagnosed with OSA and mCRC improved markedly. Conclusions: This study highlights the relevance of specific miRNAs on OSA in mCRCs and their significance as non-invasive biomarkers in predicting the prognosis in patients with mCRC and OSA.

Recording of Age-Related Changes on Murine and Human Brain Slices.

Preparation of brain slices for electrophysiological and imaging experiments has been developed several decades ago, and the method is still widely used due to its simplicity and advantages over other techniques. It can be easily combined with other well established and recently developed methods as immunohistochemistry and morphological analysis or opto- and chemogenetics. Several aspects of this technique are covered by a plethora of excellent and detailed review papers, in which one can gain a deep insight of variations in it. In this chapter, I briefly describe the solutions, equipment, and preparation techniques routinely used in our laboratory. I also aim to present how certain "old school" brain slice lab devices can be made in a cost-efficient way. These devices can be easily adapted for the special needs of the experiments. I also aim to present some differences in the preparatory techniques of acutely isolated human brain tissue.

The Association between Early-Onset Pancreatic Ductal Adenocarcinoma and Patients Survival: A Systematic Review and Meta-Analysis.

Background: In recent years, the incidence of early-onset pancreatic cancer (EOPC) has increased. Several studies comparing the survival of patients with EOPC to those with average-onset pancreatic cancer (AOPC) have reported mixed results. We aimed, therefore, to perform a meta-analysis summarizing the current evidence. Methods: We searched the MEDLINE and EMBASE databases for relevant articles published through March 2024. Articles comparing the survival of patients with EOPC - defined as pancreatic ductal adenocarcinoma (PDAC) diagnosed at ≤ 50 years of age - and AOPC were included in the present meta-analysis. The primary outcome was the pooled adjusted hazard ratio (aHR), and the risk of bias analysis was performed using the Quality in Prognostic Factor Studies tool. The meta-analysis was performed using a random-effects model. Results: A total of 17 studies were eligible for the primary analysis, the results of which indicated that patients with EOPC had a longer overall survival than those with AOPC (aHR = 0.80; 95% confidence interval [CI], 0.74-0.86; P < 0.001). The rate of distant metastasis was higher in EOPC than AOPC; however, patients with EOPC also received more treatments than those with AOPC. Conclusions: Patients with EOPC had a better prognosis than those with AOPC. Clinicians must ensure that patients with PDAC receive early and appropriate treatment to improve their survival.

Defining the Etiology of Renal Allograft Dysfunction Using Banff 2019 Classification: Correlation with Post-Transplant Duration and Creatinine Levels-A Comprehensive Analysis of 200 Renal Biopsies at a Tertiary Care Medical Center Hospital.

OBJECTIVE: Chronic kidney disease is a growing global health issue, contributing significantly to morbidity and mortality. The incidence of end-stage renal disease (ESRD) is approximately 100 per million population. Renal transplantation remains the cornerstone treatment for ESRD, with a projected 20-year survival rate of 60%. We aim to define the etiology of renal allograft dysfunction using the Banff 2019 classification by analyzing 200 renal allograft biopsies in correlation with creatinine levels across post-transplant time frames. METHODOLOGY: 200 renal allograft biopsies are analyzed using the recent Banff 2019 classification with creatinine levels and post-transplant duration correlation. RESULTS: The study included 150 (75%) male patients and 50 (25%) female patients, with the majority 78 (39%) representing the age group of 16-30 years. 36 (18%) biopsies were within 3-month post-transplant, while 92 (46%) were 2-year post-transplant. According to the Banff 2019 classification, 92 (46.0%) transplant rejection biopsies were identified, with most 54 (27%) exhibiting antibody-mediated rejection (Category 2), including 40 (20%) active acute antibody-mediated rejection (ABMR) and 14 (7.0%) chronic active ABMR. T-cell-mediated rejection (TCMR; Category 4) represented 12 (6%) biopsies, including 10 (5%) acute TCMR and 2 (1%) chronic active TCMR. Category 5, the miscellaneous group, represented 100 (50%) biopsies, out of which 32 (16%) exhibited calcineurin inhibitor (CNI) toxicity, 38 (19%) acute tubular necrosis, and 8 (4%) thrombotic microangiopathy. A notable variation in the dysfunction distribution across different post-transplant time frames indicated a temporal evolution in the underlying causes of allograft dysfunction. Specific Banff categories showed a robust association with renal dysfunction, potentially contributing to the elevation of creatinine levels and renal function deterioration. CONCLUSION: Our study highlights the intricate pathophysiology of renal allograft dysfunction. Most biopsies were attributed to ABMR whereas one-third of biopsies exhibited mixed lesions (ABMR and TCMR or ABMR and calcineurin inhibitor toxicity (CNIT)). Additionally, this study suggests that renal allograft rejection remains a significant contributor to graft dysfunction. A complex interplay between histological findings, Banff classification, and renal function is noted. A significant difference in the distribution of dysfunction across post-transplant time frames is noted suggesting a temporal evolution in the etiology of allograft dysfunction. Certain Banff categories demonstrate a stronger association with renal dysfunction that may influence creatinine level increase and renal function deterioration. In correspondence to the recent Banff 2019 guidelines for diagnosing ABMR, we emphasize the role of C4d staining on immunofluorescence or immunohistochemistry in allograft biopsies as imperative for timely diagnosis and immunosuppressant therapy adjustment, ultimately enhancing graft survival. Further research is needed to elucidate the underlying mechanisms driving renal dysfunction in different Banff categories, ultimately informing personalized management strategies for patients with renal allograft dysfunction. In line with the Banff 2019 guidelines for diagnosing ABMR, this study highlights the critical role of C4d staining through immunofluorescence or immunohistochemistry in allograft biopsies for early diagnosis and timely adjustment of immunosuppressive therapy, ultimately improving graft survival.

Mitochondrial Pyruvate Carrier 1 as a Novel Prognostic Biomarker in Non-Small Cell Lung Cancer.

BACKGROUND: Abnormal mitochondrial pyruvate carrier 1 (MPC1) expression plays a key role in tumor metabolic reprogramming and progression. Understanding its significance in non-small cell lung cancer (NSCLC) is crucial for identifying therapeutic targets. METHODS: TIMER 2.0 was utilized to assess the expression of MPC1 in both normal and cancer tissues in pan-cancer. Overall survival (OS) differences between high and low MPC1 expression were analyzed in NSCLC using the Cancer Genome Atlas (TCGA) datasets. We also examined the expression of MPC1 in NSCLC cell lines using western blotting and quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). In addition, the tissue samples and clinical information of 80 patients with NSCLC from our hospital were collected. Immunohistochemistry (IHC) was used to assess MPC1 expression, and OS was evaluated using Kaplan-Meier curves and the log-rank test. Univariate and multivariate Cox regression analyses were conducted to evaluate the prognostic values of the clinical characteristics and MPC1expression. RESULTS: Analysis of public databases suggested that MPC1 was downregulated in NSCLC compared to that in normal lung tissue and predicted poor prognosis. In addition, the expression of MPC1 in NSCLC cell lines was lower than that in human bronchial epithelial (HBE) cells at both protein and mRNA levels. Further clinical analysis suggested that MPC1 expression was correlated with age, tumor T stage, and TNM stage. Kaplan-Meier analysis revealed that NSCLC patients with high MPC1 expression had a better prognosis, particularly in lung adenocarcinoma (LUAD), whereas no survival benefit was observed in lung squamous cell carcinoma (LUSC). Univariate and multivariate analyses suggested that MPC1 was an independent prognostic factor for patients with NSCLC. CONCLUSIONS: MPC1 is poorly expressed in NSCLC, particularly in LUAD, which predicts a poor prognosis and may serve as an independent prognostic factor. Further studies on MPC1 may reveal new targets for the treatment of NSCLC.

Prognostic Value of Pre-Chemoradiotherapy Pan-Immune-Inflammation Value (PIV) in Locally Advanced Nasopharyngeal Cancers.

BACKGROUND: To examine the prognostic relevance of pan-immune-inflammation value (PIV) in locally advanced nasopharyngeal carcinomas (LA-NPC) patients treated with concurrent chemoradiotherapy (CCRT) definitively. METHODS: We used receiver operating characteristic (ROC) curve analysis to determine an optimal PIV cutoff that could effectively divide the patient cohort into two distinct groups based on distant metastasis-free (DMFS) and overall survival (OS) results. For this purpose, receiver operating characteristic (ROC) curve analysis was employed. Our primary and secondary endpoints were to investigate the potential correlations between pre-CCRT PIV measurements and post-CCRT OS and DMFS outcomes, respectively. RESULTS: This retrospective cohort study included 179 LA-NPC patients. The optimal PIV cutoff was 512 (area under the curve: 74.0%; sensitivity: 70.8%, specificity: 68.6%; J-index: 0.394) in ROC curve analysis, creating two patient groups: Group-1: PIV < 512 (N = 108); vs Group-2: PIV ≥ 512 (N = 71). In the comparative analysis, although there were no significant differences between the two groups regarding the patient, disease, and treatment characteristics, the PIV ≥ 512 group had significantly poorer median OS [74.0 months vs not reached yet (NR); HR: 2.81; P < 0.001] and DMFS (27.0 months vs NR; HR: 3.23; P < 0.001) than the PIV < 512 group. Apart from PIV ≥ 512, the N2-3 nodal stage and ≥ 5% weight loss within the preceding 6 months were significant predictors of unfavorable outcomes for DMFS (P < 0.05 for each) and OS (P < 0.05 for each) in univariate analyses. The results of the multivariate analysis showed that each of the three variables had independent negative impacts on both DMFS and OS outcomes (P < 0.05 for each). CONCLUSIONS: The present findings indicate that PIV, which classifies these patients into two groups with significantly different DMFS and OS, might be a potent prognostic biological marker for LA-NPC patients.

MGMT methylation and its prognostic significance in inoperable IDH-wildtype glioblastoma: the MGMT-GBM study.

INTRODUCTION: The methylation of the O6-Methylguanine-DNA Methyltransferase (MGMT) promoter is a valid biomarker for predicting response to therapy with alkylating agents and, independently, prognosis in IDH-wildtype(IDH-w) glioblastoma. We aim to study the impact of its methylation in overall survival of the unresectable IDH-w glioblastoma undergoing biopsy and systemic treatment. METHODS: We collected six-year retrospective (2017-2023) data at a quaternary neurosurgery center for patients undergoing biopsy as the only surgical procedure for an unresectable IDH wildtype glioblastoma. Data was collected from patient records including neuro-oncology multidisciplinary team meeting (MDT) documentation. Patients were grouped into categories according to different types of treatment received after biopsy (no treatment, chemotherapy (CT), radiotherapy (RT), chemoradiotherapy (CRT), chemoradiotherapy with adjuvant temozolomide (CRT with adjuvant TMZ), EORTC-NCIC protocol followed by second line treatment) and according to methylation status (unmethylated (< 5%), borderline methylated (5-15%) and strongly methylated (> 15%)). Survival analysis was performed. RESULTS: 166 glioblastoma IDH wildtype patients were included in the study with mean age of 62.5 years (M: F = 1.5: 1). 70 (49.3%) patients had unmethylated MGMT status (< 5%), 29 (20.4%) patients had borderline methylated MGMT status (5-15%) and 43 (30.2%) patients had methylated MGMT status (> 15%). 36 (25.3%) patients did not receive any treatment post biopsy, 13 (9.1%) received CT only, 27 (19%) RT only, 12 (8.4%) CRT, 33 (23.2%) CRT with adjuvant TMZ, whereas 21 (14.7%) received EORTC-NCIC protocol along with second line treatment. In biopsy only group, there was no notable difference in survival outcomes among the different methylation statuses. For biopsy and any-other-form-of-treatment methylated groups showed a distinct trend of better survival compared to the borderline or unmethylated groups. Overall, methylated patients had better survival as compared to unmethylated or borderline groups. CONCLUSION: Methylated MGMT status are predictors for better overall survival in unresectable IDH wildtype glioblastoma patients undergoing biopsy and treatment regardless of the treatment modality.

Nosocomial carbapenem-drug resistant Acinetobacter baumannii, related factors and clinical outcomes in Northeast Iran.

BACKGROUND AND OBJECTIVES: Nosocomial infections, including drug-resistant Acinetobacter baumannii infections, continue to impact the health of hospitalized patients. This study sought to determine the prevalence of these infections and assess the associated risk factors and clinical outcomes in Gorgan, Iran. METHODS: A retrospective cross-sectional study was conducted on 143 infected patients with Acinetobacter baumannii in two educational hospitals in Gorgan city, Iran between 2016 and 2018. Patient information including age, gender, reason and duration of hospitalization, background of diseases, type of sample culture, symptoms, laboratory findings, prescribed antibiotics, and antibiogram were collected and analyzed. The Logistic regression and survival statistical methods were used by software of SPSS 26. RESULTS: A total of 37 patients (25.87%) died during hospitalization. The less than one year and 45-65 years age groups demonstrated more deaths (29.7%; p-value < 0.001). Being single (not being married) was found to be a risk factor in increasing the chance of death among patients (OR = 2.154, 95% CI: 1.02-4.53; p = 0.048). Hospitalization in intensive care units (ICUs) was a risk factor for the death of patients (OR = 4.655, 95% CI: 7.6-83.2). The resistance to carbapenems was reported to be an important risk factor for the death of patients. CONCLUSIONS: Acinetobacter baumannii infections, particularly those resistant to carbapenems, are a significant risk for patients in ICUs and can lead to higher mortality rates.

Machine learning-based prediction model for hypofibrinogenemia after tigecycline therapy.

BACKGROUND: In clinical practice, the incidence of hypofibrinogenemia (HF) after tigecycline (TGC) treatment significantly exceeds the probability claimed by drug manufacturers. OBJECTIVE: We aimed to identify the risk factors for TGC-associated HF and develop prediction and survival models for TGC-associated HF and the timing of TGC-associated HF. METHODS: This single-center retrospective cohort study included 222 patients who were prescribed TGC. First, we used binary logistic regression to screen the independent factors influencing TGC-associated HF, which were used as predictors to train the extreme gradient boosting (XGBoost) model. Receiver operating characteristic curve (ROC), calibration curve, decision curve analysis (DCA), and clinical impact curve analysis (CICA) were used to evaluate the performance of the model in the verification cohort. Subsequently, we conducted survival analysis using the random survival forest (RSF) algorithm. A consistency index (C-index) was used to evaluate the accuracy of the RSF model in the verification cohort. RESULTS: Binary logistic regression identified nine independent factors influencing TGC-associated HF, and the XGBoost model was constructed using these nine predictors. The ROC and calibration curves showed that the model had good discrimination (areas under the ROC curves (AUC) = 0.792 [95% confidence interval (CI), 0.668-0.915]) and calibration ability. In addition, DCA and CICA demonstrated good clinical practicability of this model. Notably, the RSF model showed good accuracy (C-index = 0.746 [95%CI, 0.652-0.820]) in the verification cohort. Stratifying patients treated with TGC based on the RSF model revealed a statistically significant difference in the mean survival time between the low- and high-risk groups. CONCLUSIONS: The XGBoost model effectively predicts the risk of TGC-associated HF, whereas the RSF model has advantages in risk stratification. These two models have significant clinical practical value, with the potential to reduce the risk of TGC therapy.

Machine learning for post-liver transplant survival: Bridging the gap for long-term outcomes through temporal variation features.

BACKGROUND: The long-term survival of liver transplant (LT) recipients is essential for optimizing organ allocation and estimating mortality outcomes. While models like the Model-for-End-Stage-Liver-Disease (MELD) predict 90-day mortality on the waiting list, they do not predict post-LT survival accurately. There is a need for predictive models that can forecast post-LT survival beyond the immediate period after transplantation. METHOD: This study introduces new temporal variation features for predicting post-LT survival during the waiting list period. Cox Proportional-Hazards regression (CoxPH), Random Survival Forest (RSF), and Extreme Gradient Boosting (XGB) models are utilized, along with patient demographics and waiting list duration. Data from 716 LT patients from the University of Minnesota CTSI (2011-2021) are used to develop, evaluate, and compare post-LT survival prediction models. RESULTS: The temporal variation features, particularly when combined with the RSF model, proved most effective in predicting post-LT survival, with a C-index of 0.71 and an IBS of 0.151. This outperformed the predictive capability of the most recent MELD score, which had a C-index of <0.51 in the same cohort. CONCLUSIONS: Incorporating temporal variation features with the RSF model enhances long-term post-LT survival predictions. These insights can assist clinicians and patients in making more informed decisions about organ allocation and understanding the utility of LT, ultimately leading to improved patient outcomes.

First-line treatment of EGFR-mutated non-small cell lung cancer with brain metastases: a systematic review and meta-analysis.

This systematic review and network meta-analysis evaluates first-line treatment options for patients with EGFR-mutant non-small cell lung cancer (NSCLC) and brain metastases. We analyzed 24 randomized controlled trials (RCTs) involving 2,682 patients, comparing various EGFR tyrosine kinase inhibitors (TKIs) and combination therapies. Direct comparisons showed that the addition of bevacizumab or chemotherapy to first-generation (1G) EGFR-TKIs improved overall survival (OS) compared to 1G TKIs alone, with HRs of 0.704 (95% CI: 0.433-0.973) and 0.682 (95% CI: 0.464-0.899), respectively. However, third-generation (3G) TKI monotherapy did not significantly improve OS compared with 1G TKIs, with an HR of 0.855 (95% CI: 0.511-1.198). Indirect comparisons suggested that the combination of 3G TKIs with chemotherapy provided the most significant improvements in OS and progression-free survival (PFS), significantly outperforming 3G TKIs, with HRs of OS 1.69 (95% CI: 1.14-3.4) and PFS 2.13 (95% CI: 1.28-3.54). Intracranial PFS was best with 1G TKIs plus bevacizumab. Our findings suggest that 3G EGFR-TKIs in combination with chemotherapy may be the most effective strategy for patients with EGFR-mutant NSCLC and brain metastases, though further head-to-head trials are needed for validation.

The clinical outcomes and prognostic factors of dedifferentiated central chondrosarcoma in extremities.

OBJECTIVE: This study was to analyze the clinical outcomes and prognostic factors of dedifferentiated central chondrosarcomas (DCCS) in extremities. METHODS: A retrospective study was conducted on 49 patients (27 males, 22 females) who underwent surgical treatment between January 2001 and March 2023 in our institution. All patients were diagnosed with dedifferentiated central chondrosarcomas by needle biopsy or postoperative histopathological examination. The general characters, treatment and clinical outcomes were recorded in the follow-up and all surgical-related complications that occurred were recorded in this study. Overall, these data were used to analyse the prognostic factors of DCCS. RESULTS: 49 patients were included in this retrospective study and there were no patients lost in the follow-up period. The median diagnosis age of all patients was 57 years old (ranging from 17 to 87) and the median follow-up time was 34 months (range, 1-289). The average tumor size was 9.6 ± 2.4 cm (3.0-15.5). Median overall survival (OS) and progression-free survival (PFS) were 34 and 23 months, respectively. The 1-year, 2-year, 5-year, and 10-year OS were 87.8% (95% CI 77.6%-98.0%), 71.4% (35/49), 28.6% (14/49) and 18.4% (9/49). And the 1-year, 2-year, 5-year, and 10-year PFS were 75.5% (95% CI 63.6%-87.4%), 49.0% (35/49), 26.5% (14/49) and 16.3% (9/49). Multiple variate analyses indicated metastasis, pathological fracture, Enneking staging and surgical margin were independent prognostic factors in extremity dedifferentiated central chondrosarcomas. CONCLUSIONS: Dedifferentiated central chondrosarcomas in extremities still had a grave prognosis. Metastasis, pathological fracture, Enneking staging, and surgical margin were independent risk factors for prognosis. EVIDENCE LEVEL: IV Therapic.

Textbook oncologic outcome is an easy-to-use composite quality measure that is strongly associated with survival in advanced-stage ovarian cancer.

OBJECTIVE: Textbook oncologic outcome (TOO) has been validated in surgical oncology as a composite quality measure correlated with oncologic outcomes. We aimed to assess the association between TOO and overall survival (OS) in patients undergoing primary treatment for advanced epithelial tubo-ovarian cancer (AEOC). METHODS: Patients undergoing surgery for AEOC between 2008 and 2019 were identified in the National Cancer Database (NCDB). Primary debulking surgery (PDS) and interval debulking surgery (IDS) cohorts were analyzed separately. TOO was defined as achieving complete debulking, length of hospital stay <10 days, no 30-day readmission, no death within 90 days, and initiation of adjuvant chemotherapy within 42 days. The Kaplan-Meier method was used to estimate 5-year OS by TOO status and Cox regression to evaluate the relationship between TOO and death within 5 years. RESULTS: A total of 21,657 patients were included: 51.4% in the PDS cohort and 48.6% in the IDS cohort. TOO was achieved (TOO+) in 20.5% of the PDS cohort and 39.2% of the IDS cohort. For the PDS cohort, achieving TOO was associated with improved 5-year OS: 59.0% TOO+ vs. 39.5% TOO- (HR 0.53, 95% CI 0.49-0.57). For the IDS cohort, a similar benefit was seen for 5-year OS: 43.9% TOO+ vs. 31.2% TOO- (HR 0.67, 95% CI 0.63-0.70). Multivariable analysis demonstrated that patients achieving TOO were at lower risk of death within 5 years in both the PDS cohort (HR 0.58, 95% CI 0.54-0.62) and the IDS cohort (HR 0.69, 95% CI 0.65-0.73). CONCLUSIONS: The TOO composite measure is associated with improved long-term survival and could be a useful quality assessment tool for patients undergoing primary treatment for AEOC, irrespective of surgical timing. This tool reflects the ability to deliver risk-based individualized decision-making using a multidisciplinary approach.

Low to intermediate grade lung neuroendocrine tumours. A single centre real world experience.

INTRODUCTION: Lung neuroendocrine tumours (LNETs) are a rare heterogenous group of tumours whose incidence has been increasing. We investigated the diagnosis, treatment, and survival patterns of patients with low to intermediate grade LNETs. METHODS: A retrospective chart review of patients with low to intermediate grade LNETs, treated at a Canadian tertiary-level cancer centre was performed. RESULTS: We identified 59 patients. Most were G1or G2 and well or moderately differentiated. Forty-seven patients presented with local or locally advanced disease, of which 57.4 % received curative intent surgery. The rest were treated with definitive radiation, radical chemoradiation with platinum and etoposide, palliative chemotherapy with doxorubicin, or supportive care. The five-year overall survival (OS) for those treated surgically was 83 % versus 44 % in the non-surgical group. Metastatic disease was seen in 24/59 patients, with a five-year OS in patients with stage IV disease of 39 %. Of those with advanced or unresectable disease (n = 32), 21 received palliative systemic treatment with up to three lines of therapy. First-line treatment was most commonly chemotherapy with platinum/etoposide combination or somatostatin analogue therapy. Second-line treatment involved chemotherapy or targeted everolimus. PRRT was used once as a first-line and once as second-line therapy. Third-line included lanreotide or chemotherapy with capecitabine/temozolomide combination. CONCLUSION: Overall, patients with surgically resectable disease had a good five-year OS. However, inoperable or more advanced disease was associated with a poorer OS. Despite many treatment options, the sequence of treatments is poorly established. This highlights the need for further development and dissemination of evidence-based guidelines for LNET patients.

Beyond the urban-rural divide: Exploring spatial variations in breast cancer outcomes in Queensland, Australia.

BACKGROUND: Breast cancer is the most commonly diagnosed cancer among women worldwide. While previous studies have reported urban and rural differences in breast cancer outcomes, the level of heterogeneity within these broad regions is currently unknown. METHODS: Population-level data from Queensland Cancer Register including 58,679 women aged at least 20 years who were diagnosed with breast cancer in Queensland, Australia, 2000-2019 were linked to BreastScreen Queensland and Queensland Hospital Admitted Patients Data Collection to estimate five breast cancer outcomes: incidence, proportion of localised disease and screen-detected cases (via public-funded program), surgical rates, and 5-year survival. Bayesian spatial models were used to smooth outcomes across 512-517 small areas in Queensland. RESULTS: The incidence of breast cancer was not proportionally distributed, with urban regions having higher rates. Less than half (47 %) of women were diagnosed with localised disease, 91 % had surgery, with five-year relative survival of 92 %. There was no evidence of geographic variation in the proportion of localised disease, surgical rates, or survival over Queensland. Publicly-funded screening detected 38 % of cases, with lower proportion of screen-detected cases observed in Queensland's urbanised south-east corner. CONCLUSION: Although the disparities in health outcomes faced by Australians living in rural areas have received increased attention, this study found limited evidence for spatial variation in breast cancer outcomes along the continuum of care across Queensland. These results suggest the detection and management practices for breast cancer may provide an achievable benchmark for other cancer types in reducing the geographical disparity in cancer outcomes.

Protective effect of aspirin and gentisic acid, a plant-derived phenolic acid, on acrylamide-induced neurotoxicity by inhibiting apoptosis and autophagy.

Acrylamide (ACR) is a toxic agent for humans and animals. Gentisic acid, an aspirin metabolite, has antioxidant activity. Therefore, the present study investigated the probable protective effects of aspirin and gentisic acid on ACR-induced neurotoxicity in PC12 cells and rats. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay was used to assess the effects of aspirin and gentisic acid (1.25, 2.5, 5 µM) on ACR (5 mM) toxicity. Male Wistar rats were randomly divided into 13 groups: (1) Control group, (2) ACR (50 mg/kg, 11 days, i.p.), (3-5) ACR + aspirin (25, 50, 75 mg/kg, 11 days, p.o.), (6-8) ACR + gentisic acid (25, 50, 75 mg/kg, 11 days, p.o.), (9) ACR + vitamin E (200 mg/kg, every other day, i.p.), (10, 11) Aspirin (75, 100 mg/kg, 11 days, p.o.), (12, 13) Gentisic acid (75, 100 mg/kg, 11 days, p.o.). Behavioral tests were assessed on the final day of the study. In the cerebral cortex, malondialdehyde (MDA), glutathione (GSH), cleaved-caspase-3, and microtubule-associated protein 1A/1B-light chain 3 (LC3) protein levels were evaluated. When compared with the ACR group, aspirin (2.5, 5 µM) and gentisic acid (2.5 µM) significantly enhanced cell viability. In comparison to the control group, ACR induced severe motor impairment, elevated MDA, cleaved-caspase-3, LC3 II/I ratio, and decreased GSH levels in the cerebral cortex of rats. ACR-induced changes were significantly reversed by aspirin and gentisic acid (25 mg/kg). Oxidative stress, apoptosis, and autophagy play important roles in the neurotoxicity of ACR. Aspirin and gentisic acid significantly reduced ACR-induced toxicity by inhibiting the mentioned mechanisms.

Adjuvant immunotherapy in older patients with stage III and resected stage IV melanoma: Toxicity and recurrence-free survival outcomes from the Dutch melanoma treatment registry.

BACKGROUND: Adjuvant anti-PD-1 therapy improves relapse free survival in stage III melanoma, but also leads to immune-related adverse events (irAEs). Older patients are of particular interest due to comorbidities and frailty, which may impact their ability to tolerate irAEs and benefit from anti-PD-1 therapy. This study aimed to explore associations between clinical parameters and the occurrence of grade ≥ 3 irAEs and recurrence-free survival (RFS) in older patients with radically resected stage III/IV cutaneous melanoma treated with adjuvant anti-PD-1 therapy. METHODS: Patients aged ≥ 65 with resected stage III/IV cutaneous melanoma treated with adjuvant anti-PD-1 therapy between 2018 and 2022 were selected using real-world data from the nationwide Dutch Melanoma Treatment Registry (DMTR). A univariate and multivariable logistic regression was used to compare determinants of grade ≥ 3 irAEs, and univariate and multivariable Cox-proportional hazard models were fitted to identify factors influencing RFS. RESULTS: The study included 885 patients, with 280 aged 75 and older. The incidence of grade ≥ 3 irAEs was 15.5 % in the 65-74 age group and 13.9 % in the ≥ 75 age group. No significant correlation was found between age and grade ≥ 3 irAEs. However, an increasing number of comorbidities was associated with a higher risk of grade ≥ 3 irAEs (multivariable analyses: OR 1.83, 95 % C.I. 0.99-3.40). The 1-year RFS rate of 80.0 % of this study was comparable to those reported in previous registration trials and real-world data. Having ≥ 3 comorbidities was significantly associated with a decrease in RFS (HR: 1.68, 95 % C.I. 1.15-2.44). CONCLUSION: Older patients had similar benefit of adjuvant immunotherapy compared to older subgroups in previous trials. However, patients with multiple comorbidities were at increased risk of grade ≥ 3 irAEs and had a lower RFS. This should be considered when deciding upon adjuvant treatment.

Lateral lymph node metastasis without mesenteric lymph node involvement in middle-low rectal cancer: Results of a multicentre lateral node collaborative group study in China.

BACKGROUND: Characteristics and prognoses of lateral lymph node (LLN) metastasis but not mesenteric lymph node (LN) metastasis are poorly understood. This study explored patterns of mesenteric and LLN metastases in rectal cancer patients. METHOD: This retrospective, multicentre study was conducted at three institutions and included patients who underwent total mesorectal excision (TME) with lateral lymph node dissection (LLND) for rectal cancer (n = 271). RESULTS: Among the patients with LLN metastases, 210 patients (77.5 %) with clinical stage T3-4 disease and 157 patients (57.9 %) with clinical stage N1-N2 disease underwent TME as well as LLND. The prognoses of patients with metastasis confined to LLNs were significantly better than those of patients with both mesenteric and LLN metastases (3-year overall survival: 85.0 % vs. 51.0 %, p = 0.005; 3-year disease-free survival: 75.0 % vs. 26.5 %, p = 0.003) and were similar to those of patients with metastasis confined to mesenteric LNs (3-year overall survival: 85.0 % vs. 83.8 %, p = 0.607; 3-year disease-free survival 75.0 % vs. 68.8 %, p = 0.717). Patients with metastases confined to LLN had a lower proportion of poor histological types (20.0 % vs. 65.3 %, p = 0.002), lymphatic invasion (20.0 % vs. 59.2 %, p = 0.036) and number of LLN metastases (1.6 vs 2.7, p = 0.004), and all metastases were confined to the internal iliac or obturator region (100.0 % vs. 77.6 %, p = 0.008) compared to patients with both mesenteric and LLN metastasis. CONCLUSIONS: Approximately a quarter of patients with rectal cancer have LLN metastases but no mesenteric LN metastases. These patients have favourable pathological features and prognoses and can be managed and treated for mesenteric LN metastasis.