Analysis of risk characteristics for early progression and late progression in locally advanced rectal cancer patients: a large population-based and validated study.

BACKGROUND AND OBJECTIVE: The current study aimed to explore the factors influencing early progression (EP) and late progression (LP) in locally advanced rectal cancer (LARC) patients. METHODS: The patients were classified into EP and LP groups using one year as a cutoff. The random survival forest model was utilized to calculate the probability of time-to-progression. Besides, inverse probability of treatment weighting (IPTW) analysis and the Surveillance, Epidemiology, and End Results (SEER) were conducted to validate our results. RESULTS: Our study revealed that PNI, CEA level, and pathological stage were independent prognostic factors for PFS both in EP group and LP group. For EP group patients, Group 1 had the highest probability of progression at the 9th month of follow-up, while Group 2 exhibited the highest probability at the 6th month. Group 3, on the other hand, showed two peaks of progression at the 4th and 8th months of follow-up. As for LP group patients, Groups 4, 5, and 6 all exhibited peaks of progression between the 18th and 24th months of follow-up. Furthermore, our results suggested that PNI was also an independent prognostic factor affecting OS in both EP group and LP group. Finally, the analysis of IPTW and SEER database further confirmed our findings. CONCLUSIONS: Our results indicated a significant correlation between immune and nutritional status with PFS and OS in both EP and LP groups. These insights can aid healthcare professionals in effectively identifying and evaluating patients' nutritional status, enabling them to develop tailored nutrition plans and interventions.

Excluding external iliac node irradiation during neoadjuvant radiotherapy decreases lower intestinal toxicity without compromising efficacy in T4b rectal cancer patients with tumours involving the anterior structures.

PURPOSE: To explore the impact of excluding the external iliac node (EIN) from the clinical target volume (CTV) during preoperative radiotherapy in T4b rectal cancer with anterior structure invasion. METHODS: We retrospectively identified 132 patients with T4b rectal cancer involving the anterior structures who received radiotherapy followed by surgery between May 2010 and June 2019. Twenty-nine patients received EIN irradiation (EIN group), and 103 did not (NEIN group). Failure patterns, survival and toxicities were compared between the two groups. RESULTS: The most common failure was distant metastasis (23.5%). 11 (8.3%) patients developed locoregional recurrence, 10 (9.7%) patients were in the NEIN group, and 1 (3.4%) was in the EIN group (P = 0.34). The EIN region failure was rare (1/132, 0.8%). The locoregional recurrence-free survival (LRFS), distant metastasis-free survival (DMFS), overall survival (OS) and progression-free survival (PFS) rates were 96.3% vs. 90.5%, 82.1% vs.73.7%, 75.9% vs. 78.0% and 72.4% vs. 68.3% (all P > 0.05) for the EIN group and NEIN group, respectively. The incidence of grade 3-4 acute toxicity in the lower intestine was significantly higher in the EIN group than in the NEIN group (13.8% vs. 1.9%, P = 0.02). The Dmax, V35 and V45 of the small bowel was decreased in the NEIN group compared to the EIN group. CONCLUSIONS: Exclusion of the EIN from the CTV in T4b rectal cancer with anterior structure invasion could reduce lower intestinal toxicity without compromising oncological outcomes. These results need further evaluation in future studies.

Prediction of liver metastasis and recommended optimal follow-up nursing in rectal cancer.

We aimed to analyze and investigate the clinical factors that influence the occurrence of liver metastasis in locally advanced rectal cancer patients, with an attempt to assist patients in devising the optimal imaging-based follow-up nursing. Between June 2011 and May 2021, patients with rectal cancer at our hospital were retrospectively analyzed. A random survival forest model was developed to predict the probability of liver metastasis and provide a practical risk-based approach to surveillance. The results indicated that age, perineural invasion, and tumor deposit were significant factors associated with the liver metastasis and survival. The liver metastasis risk of the low-risk group was higher at 6-21 months, with a peak occurrence time in the 15th month. The liver metastasis risk of the high-risk group was higher at 0-24 months, with a peak occurrence time in the 8th month. In general, our clinical model could predict liver metastasis in rectal cancer patients. It provides a visualization tool that can aid physicians and nurses in making clinical decisions, by detecting the probability of liver metastasis.

Disulfidptosis-related prognostic signature correlates with immunotherapy response in colorectal cancer.

Disulfidptosis (DSP), a form of cell death caused by disulphide stress, plays an important role in tumour progression. However, the mechanisms by which DSP regulates the tumour microenvironment remain unclear. Thus, we analysed the transcriptome profiles and clinical data, which were obtained from the TCGA database, of 540 patients with colorectal cancer. Compared with the patients with low DSP expression, those with high DSP expression exhibited significantly better survival outcomes; lower stromal and ESTIMATE scores; significantly higher numbers of CD4+ T cells, M2 macrophages, dendritic cells, and neutrophils; higher expression of immune checkpoint-related genes; and lower Tregs and HLA-DQB2 levels. A prognostic signature established based on DSP-related genes demonstrated an increase in risk score with a higher clinical stage. Risk scores negatively correlated with dendritic cells, eosinophils, and CD4+ T cells and significantly positively correlated with Treg cells. Patients with higher risk scores experienced significantly worse survival outcomes and immunotherapy non-response. Our nomogram model, combining clinicopathological features and risk scores, exhibited robust prognostic and predictive power. In conclusion, DSP-related genes actively participated in regulating the tumour microenvironment. Thus, they can serve as biomarkers to provide targeted treatment for colorectal cancer.

STING Agonist-Loaded Nanoparticles Promotes Positive Regulation of Type I Interferon-Dependent Radioimmunotherapy in Rectal Cancer.

Hypoxia-associated radioresistance in rectal cancer (RC) has severely hampered the response to radioimmunotherapy (iRT), necessitating innovative strategies to enhance RC radiosensitivity and improve iRT efficacy. Here, a catalytic radiosensitizer, DMPtNPS, and a STING agonist, cGAMP, are integrated to overcome RC radioresistance and enhance iRT. DMPtNPS promotes efficient X-ray energy transfer to generate reactive oxygen species, while alleviating hypoxia within tumors, thereby increasing radiosensitivity. Mechanistically, the transcriptomic and immunoassay analysis reveal that the combination of DMPtNPS and RT provokes bidirectional regulatory effects on the immune response, which may potentially reduce the antitumor efficacy. To mitigate this, cGAMP is loaded into DMPtNPS to reverse the negative impact of DMPtNPS and RT on the tumor immune microenvironment (TiME) through the type I interferon-dependent pathway, which promotes cancer immunotherapy. In a bilateral tumor model, the combination treatment of RT, DMPtNPS@cGAMP, and αPD-1 demonstrates a durable complete response at the primary site and enhanced abscopal effect at the distant site. This study highlights the critical role of incorporating catalytic radiosensitizers and STING agonists into the iRT approach for RC.

A Modified NAR Scoring Model Incorporating Immune Infiltration Characteristics to Better Predict Long-Term Survival Following Neoadjuvant Radiotherapy in Rectal Cancer.

(1) Background: The neoadjuvant rectal (NAR) score has been developed as a prognostic tool for survival in locally advanced rectal cancer (LARC). However, the NAR score only incorporates weighted cT, ypT, and ypN categories. This long-term follow-up study aims to modify a novel prognostic scoring model and identify a short-term endpoint for survival. (2) Methods: The prognostic factors for overall survival (OS) were explored through univariate and multivariate analyses. Based on Cox regression modeling, nomogram plots were constructed. Area under the curve (AUC) and concordance indices were used to evaluate the performance of the nomogram. Receiver operating characteristic (ROC) analysis was conducted to compare the efficiency of the nomogram with other prognostic factors. (3) Results: After a long-term follow-up, the 5-year OS was 67.1%. The mean NAR score was 20.4 ± 16.3. Multivariate analysis indicated that CD8+ T-cell, lymphovascular invasion, and the NAR score were independent predictors of OS. The modified NAR scoring model, incorporating immune infiltration characteristics, exhibited a high C-index of 0.739 for 5-year OS, significantly outperforming any individual factor. Moreover, the predictive value of the nomogram was superior to the AJCC stage and pathological complete regression at 3-year, 5-year, and 10-year time points, respectively. Over time, the model's predictions of long-term survival remained consistent and improved in accuracy. (4) Conclusions: The modified NAR scoring model, incorporating immune infiltration characteristics, demonstrates high accuracy and consistency in predicting OS.

A large-scale study integrating nutritional indicators and clinicopathological parameters to evaluate prognosis, follow-up, and postoperative chemotherapy decisions in rectal cancer patients.

OBJECTIVE: The aim of this study was to evaluate the role of nutritional indicators and clinicopathological parameters in predicting the progression and prognosis for pathological stage II-III rectal cancer (RC) patients without neoadjuvant radiotherapy. In addition, we sought to explore the high-risk population who may require postoperative chemotherapy. METHODS: A total of 894 consecutive RC patients were enrolled in this study. Univariate and multivariate Cox analysis were performed to identify the independent risk factors for PFS and OS. The nomogram and calibration curves were conducted according to multivariable analysis result. Kaplan-Meier survival curves and log-rank tests were performed for different groups. Finally, random survival forest (RSF) model was developed to predict the probability of progression. RESULTS: Our results revealed that CEA level, pathological stage, tumor deposit, and PNI were independently associated with PFS in RC patients. Similarly, the results indicated that CEA level, pathological stage, tumor deposit, PNI, and NRI were independently associated with OS. RSF model revealed that group 1 had the highest risk of progression at the 12th month of follow-up, group 2 had the highest risk of progression at the 15th month of follow-up, while group 3 had the highest risk of progression at the 9th month of follow-up. Besides, subgroup analysis suggested that the high-risk group needs postoperative adjuvant chemotherapy, while patients in the low- and moderate-risk groups may not need postoperative adjuvant chemotherapy. Finally, we validated our results with the SEER database. CONCLUSIONS: In conclusion, we demonstrated that preoperative nutritional indicator and clinicopathological parameters could act as auxiliary prognostication tools for RC patients without neoadjuvant radiotherapy. We also established follow-up strategies for different groups of patients. Collectively, incorporating nutritional assessment into risk stratification for RC resection is crucial and should be an integral part of preoperative planning.

Methylglyoxal from gut microbes boosts radiosensitivity and radioimmunotherapy in rectal cancer by triggering endoplasmic reticulum stress and cGAS-STING activation.

BACKGROUND: Preoperative radiation therapy (preRT) is a fundamental aspect of neoadjuvant treatment for rectal cancer (RC), but the response to this treatment remains unsatisfactory. The combination of radiation therapy (RT) and immunotherapy (iRT) presents a promising approach to cancer treatment, though the underlying mechanisms are not yet fully understood. The gut microbiota may influence the response to RT and immunotherapy. Therefore, we aimed to identify the metabolism of gut microbiota to reverse radioresistance and enhance the efficacy of iRT. METHODS: Fecal and serum samples were prospectively collected from patients with locally advanced rectal cancer (LARC) who had undergone pre-RT treatment. Candidate gut microbiome-derived metabolites linked with radiosensitization were screened using 16s rRNA gene sequencing and ultrahigh-performance liquid chromatography-mass coupled with mass spectrometry. In vitro and in vivo studies were conducted to assess the radiosensitizing effects of the metabolites including the syngeneic CT26 tumor model and HCT116 xenograft tumor model, transcriptomics and immunofluorescence. The CT26 abscopal effect modeling was employed to evaluate the combined effects of metabolites on iRT. RESULTS: We initially discovered the gut microbiota-associated metabolite, methylglyoxal (MG), which accurately predicts the response to preRT (Area Under Curve (AUC) value of 0.856) among patients with LARC. Subsequently, we observed that MG amplifies the RT response in RC by stimulating intracellular reactive oxygen species (ROS) and reducing hypoxia in the tumor in vitro and in vivo. Additionally, our study demonstrated that MG amplifies the RT-induced activation of the cyclic guanosine monophosphate AMP synthase-stimulator of interferon genes pathway by elevating DNA double-strand breaks. Moreover, it facilitates immunogenic cell death generated by ROS-mediated endoplasmic reticulum stress, consequently leading to an increase in CD8+ T and natural killer cells infiltrated in the tumor immune microenvironment. Lastly, we discovered that the combination of anti-programmed cell death protein 1 (anti-PD1) therapy produced long-lasting complete responses in all irradiated tumor sites and half of the non-irradiated ones. CONCLUSIONS: Our research indicates that MG shows promise as a radiosensitizer and immunomodulator for RC. Furthermore, we propose that combining MG with iRT has great potential for clinical practice.

A high propensity for excessive daytime sleepiness independent of lifestyle is associated with cognitive performance in community-dwelling older adults.

Objective: The relationship between excessive daytime sleepiness (EDS) and cognitive performance of older adults remains unclear, especially when a healthy lifestyle is considered. The study aimed to explore the association between EDS in passive and active situations and general cognitive function among community-dwelling older adults. Methods: Two hundred and seventy-one older adults aged 60 and above were recruited from the community cohort in Shangrao. All study participants were free of depression and dementia. The Chinese version of the Epworth Sleepiness Scale (CESS) was used to evaluate EDS. Using the item scores of CESS, the presence of EDS among all study participants were grouped as non-EDS, passive situation-related EDS (PSR-EDS), active situation-related EDS (ASR-EDS), and high sleep propensity (HSP). The Hong Kong Brief Cognitive Test (HKBC) was used to assess cognitive function. Chinese healthy lifestyle metrics were scored based on AHA Life Simple-7. The multivariate logistic regression model was used to estimate the association between the presence of EDS and cognitive function. Results: The PSR-EDS (n = 29, 20.8 ± 5.3) and the HSP groups (n = 21, 19.8 ± 4.8) scored lower with HKBC than in the non-EDS group (n = 213, 23.2 ± 4.9). The subdomain performance of language in the HSP group was poorer than in the non-EDS group (ps < 0.05). Relative to non-EDS, HSP (OR = 3.848, 95% CI = 1.398-10.591) was associated with an increased risk of poor cognitive performance after adjusting age, sex, education, and healthy lifestyle metrics. Conclusion: High propensity for excessive daytime sleepiness, irrespective of lifestyle, is associated with poorer cognitive performance among community-dwelling older adults. The findings may provide empirical evidence to support sleepiness intervention for reducing the risk of cognitive decline.

Development and validation of a novel prognostic signature based on m6A/m5C/m1A-related genes in hepatocellular carcinoma.

BACKGROUND: RNA methylation modification plays an important role in cancers. This study sought to examine the association between m6A/m5C/m1A-related genes and hepatocellular carcinoma (HCC). METHODS: Gene expression and clinical data of HCC patients were obtained from the TCGA database. Unsupervised consensus clustering was performed according to the expression of m6A/m5C/m1A-related genes in HCC. The relationships among prognosis, clinicopathological features and molecular subtypes were analyzed. Least absolute shrinkage and selection operator (LASSO) regression analysis was used to establish the m6A/m5C/m1A-related gene prognostic signature. Furthermore, the prognostic signature was validated based on the ICGC dataset. RT‒qPCR was used to detect the expression of the model genes in HCC. Clinicopathological features, functional enrichment, gene mutations, immune cell infiltration, and immunotherapy response in different risk groups were analyzed. A nomogram based on risk score and stage was constructed to predict HCC patient prognosis. RESULTS: Two m6A/m5C/m1A-related molecular subtypes were identified in HCC, and the prognosis of cluster C1 was worse than that of cluster C2 (p < 0.001). Highly expressed genes in cluster C1 are significantly correlated with G3-4, T3-4, stage III-IV (p < 0.05). An m6A/m5C/m1A-related prognostic signature was established and validated. The RT‒qPCR results showed that the risk signature genes were significantly upregulated in liver cancer tissue (p < 0.05). The prognosis of HCC patients in the high-risk group was worse than that of those in the low-risk group (p < 0.05). Multivariate Cox analysis indicated that the risk score was an independent factor predicting prognosis in HCC patients. ssGSEA revealed that the risk score correlated with the tumor immune microenvironment in HCC. Gene mutation analysis showed that the tumor mutation burden of patients in the high-risk group was much higher (p < 0.05), and the prognosis of HCC patients with high risk scores and high mutation burden was the worst (p = 0.007). A nomogram combining risk scores with clinicopathological features showed performed well in predicting HCC prognosis. CONCLUSIONS: The m6A/m5C/m1A-related genes could predict the prognosis and tumor microenvironment features of HCC and can be important biomarkers relevant to the immunotherapy response.

Outcome and risk prediction of early progression in patients with extranodal natural killer/T cell lymphoma from the CLCG study.

Recently, progression-free survival at 24 months (PFS24) was defined as clinically relevant for patients with extranodal NK/T cell lymphoma. Herein, the clinical data from two independent random cohorts (696 patients each in the primary and validation datasets) were used to develop and validate a risk index for PFS24 (PFS24-RI), and evaluate its ability to predict early progression. Patients achieving PFS24 had a 5-year overall survival (OS) of 95.8%, whereas OS was only 21.2% in those failing PFS24 (P<0.001). PFS24 was an important predictor of subsequent OS, independent of risk stratification. The proportion of patients achieving PFS24 and 5-year OS rates correlated linearly among risk-stratified groups. Based on multivariate analysis of the primary dataset, the PFS24-RI included five risk factors: stage II or III/IV, elevated lactate dehydrogenase, Eastern Cooperative Oncology Group score ≥2, primary tumor invasion, and extra-upper aerodigestive tract. PFS24-RI stratified the patients into low-risk (0), intermediate-risk (1-2), high-risk (≥3) groups with different prognoses. Harrell's C-index of PFS24-RI for PFS24 prediction was 0.667 in the validation dataset, indicating a good discriminative ability. PFS24-RI calibration indicated that the actual observed and predicted probability of failing PFS24 agreed well. PFS24-RI provided the probability of achieving PFS24 at an individual patient level.

A novel anoikis-related gene prognostic signature and its correlation with the immune microenvironment in colorectal cancer.

Background: Anoikis is a type of apoptosis associated with cell detachment. Resistance to anoikis is a focal point of tumor metastasis. This study aimed to explore the relationship among anoikis-related genes (ARGs), immune infiltration, and prognosis in colorectal cancer (CRC). Methods: The transcriptome profile and clinical data on patients with CRC were retrieved from The Cancer Genome Atlas and Gene Expression Omnibus databases. Patients were divided into two clusters based on the expression of ARGs. Differences between the two ARG molecular subtypes were analyzed in terms of prognosis, functional enrichment, gene mutation frequency, and immune cell infiltration. An ARG-related prognostic signature for predicting overall survival in patients with CRC was developed and validated using absolute value convergence and selection operator (LASSO) regression analysis. The correlation between the signature risk score and clinicopathological features, immune cell infiltration, immune typing, and immunotherapy response was analyzed. The risk score combined with clinicopathological characteristics was used to construct a nomogram to assess CRC patients' prognosis. Results: Overall, 151 ARGs were differentially expressed in CRC. Two ARG subtypes, namely, ARG-high and ARG-low groups, were identified and correlated with CRC prognosis. The gene mutation frequency and immune, stromal, and ESTIMATE scores of the ARG-high group were higher than those of the ARG-low group. Moreover, CD8, natural killer cells, M1 macrophages, human leukocyte antigen (HLA), and immune checkpoint-related genes were significantly increased in the ARG-high group. An optimized 25-gene CRC prognostic signature was successfully constructed, and its prognostic predictive ability was validated. The high-risk score was correlated with T, N, M, and TNM stages. Risk scores were negatively correlated with dendritic cells, eosinophils, and CD4 cells, and significantly positively correlated with regulatory T cells. Patients in the high-risk group were more likely to exhibit immune unresponsiveness. Finally, the nomogram model was constructed and showed good prognostic predictive power. Conclusion: ARGs are associated with clinicopathological features and the prognosis of CRC, and play important roles in the immune microenvironment. Herein, we underpinned the usefulness of ARGs in CRC to develop more effective immunotherapy techniques.

A positive feedback loop between ID3 and PPARγ via DNA damage repair regulates the efficacy of radiotherapy for rectal cancer.

OBJECTIVE: To study the effect of inhibitor of differentiation 3 (ID3) on radiotherapy in patients with rectal cancer and to explore its primary mechanism. METHODS: Cell proliferation and clonogenic assays were used to study the relationship between ID3 and radiosensitivity. Co-immunoprecipitation and immunofluorescence were performed to analyze the possible mechanism of ID3 in the radiosensitivity of colorectal cancer. At the same time, a xenograft tumor model of HCT116 cells in nude mice was established to study the effect of irradiation on the tumorigenesis of ID3 knockdown colorectal cancer cells in vivo. Immunohistochemistry was performed to analyze the relationship between ID3 expression and the efficacy of radiotherapy in 46 patients with rectal cancer. RESULTS: Proliferation and clonogenic assays revealed that the radiosensitivity of colorectal cancer cells decreased with ID3 depletion through p53-independent pathway. With the decrease in ID3 expression, MDC1 was downregulated. Furthermore, the expression of ID3, MDC1, and γH2AX increased and formed foci after irradiation. ID3 interacted with PPARγ and form a positive feedback loop to enhance the effect of ID3 on the radiosensitivity of colorectal cancer. Irradiation tests in nude mice also confirmed that HCT116 cells with ID3 knockdown were more affected by irradiation. Immunohistochemical study showed that rectal cancer patients with low expression of ID3 had better radiotherapy efficacy. CONCLUSIONS: ID3 and PPARγ influence the radiosensitivity of colorectal cancer cells by interacting with MDC1 to form a positive feedback loop that promotes DNA damage repair. Patients with low expression of ID3 who received neoadjuvant chemoradiotherapy can obtain a better curative effect.

Clinical characteristics, treatment, and survival of 30 patients with gastrointestinal natural killer/T-cell lymphoma.

BACKGROUND: The gastrointestinal (GI) tract is the second most frequent extranasal involvement site for ENKTL. This study aimed to explore the clinicopathological features, treatment models, survival outcomes, and prognosis of gastrointestinal ENKTL (GI-ENKTL). METHODS: The clinical data of GI-ENKTL patients were extracted from the China Lymphoma Collaborative Group (CLCG) database and were analyzed retrospectively. RESULTS: A total of 30 patients were enrolled, with a male/female ratio of 4:1 and a median age of 42 years. Twenty-nine patients received chemotherapy, of whom 15 patients received asparaginase-based (ASP-based) regimens. Moreover, seven received surgery and three received radiotherapy. The overall response an d complete remission rates were 50.0% and 30.0% for the whole cohort, 50.0% and 37.5% for patients treated with ASP-based regimens, and 50.0% and 25.0% for those treated with non-ASP-based regimens, respectively. The median follow-up was 12.9 months and the 1-year overall survival rate was 40.0% for the whole cohort. For those patients in an early stage, ASP-based regimens resulted in a superior 1-year progression-free survival rate compared to non-ASP-based regimens (100.0% vs. 36.0%, p = .07). However, ASP-based regimens did not improve survival in patients at an advanced stage. CONCLUSION: GI-ENKTL still has a poor prognosis, even in the era of modern asparaginase-based treatment strategies.

A facile approach to obtain super-hydrophobicity for cotton fiber fabrics.

It is a challenging task to directly apply emulsified silicone oil to the surface of cotton fabric to obtain superhydrophobic properties. In this work, a temperature-responsive microgel was first synthesized and the particle size and distribution of the microgel, thermo-responsiveness, and hydrophobicity of the microgel membrane were investigated. Then, through an emulsifying PMHS/water system with microgels as a Pickering emulsifier, a series of Pickering emulsions were obtained. The results showed that the emulsion had the best stability when the microgel content was 2.14 wt% and the mass ratio of PMHS/water was 3/7. The optical microscopy showed that the oil phase could be uniformly dispersed in aqueous solution, and the liquid phase particle size was about 10-22 µm. And stratification of the Pickering emulsion did not occur when placed at room temperature for over one month. Finally, when the addition of Pickering emulsion is 50 g L-1 and the rolling rate is 80%, through a simple two-dip-two-padding treatment, a cotton fabric can obtain the superhydrophobic effect with a static contact angle of 149.6° at 25 °C and 156.4° at 45 °C. The development of this work provides a simple method to make cotton fabric obtain superhydrophobic effects.

Evidence of cure for extranodal nasal-type natural killer/T-cell lymphoma with current treatment: an analysis of the CLCG database.

Survival from extranodal nasal-type NK/T-cell lymphoma (ENKTCL) has substantially improved over the last decade. However, there is little consensus as to whether a population of patients with ENKTCL can be considered "cured" of the disease. We aimed to evaluate the statistical "cure" of ENKTCL in the modern treatment era. This retrospective multicentric study reviewed the clinical data of 1,955 patients with ENKTCL treated with non-anthracycline-based chemotherapy and/or radiotherapy in the China Lymphoma Collaborative Group multicenter database between 2008 and 2016. A non-mixture cure model with incorporation of background mortality was fitted to estimate cure fractions, median survival times and cure time points. The relative survival curves attained plateau for the entire cohort and most subsets, indicating that the notion of cure was robust. The overall cure fraction was 71.9%. The median survival was 1.1 years in uncured patients. The cure time was 4.5 years, indicating that beyond this time, mortality in ENKTCL patients was statistically equivalent to that in the general population. Cure probability was associated with B symptoms, stage, performance status, lactate dehydrogenase, primary tumor invasion, and primary upper aerodigestive tract site. Elderly patients (>60 years) had a similar cure fraction to that of younger patients. The 5-year overall survival rate correlated well with the cure fraction across risk-stratified groups. Thus, statistical cure is possible in ENKTCL patients receiving current treatment strategies. Overall probability of cure is favorable, though it is affected by the presence of risk factors. These findings have a high potential impact on clinical practice and patients' perspective.

Characteristics and prognosis of distant metastasis after primary treatment for early-stage extranodal nasal-type natural killer/T-cell lymphoma from the China Lymphoma Collaborative Group database.

This study aimed to investigate the characteristics and prognosis of distant metastasis (DM) after primary treatment for early-stage extranodal nasal-type natural killer (NK)/T-cell lymphoma (ENKTCL). A total of 1619 patients from the China Lymphoma Collaborative Group database were retrospectively reviewed. The cumulative incidence of DM was assessed using Fine and Gray's competing risk analysis. The correlation between DM sites was evaluated using phi coefficients, while DM sites were classified using hierarchical clustering. Regression analysis was used to assess the linear correlation between DM-free survival (DMFS) and overall survival (OS). The 5-year cumulative DM rate was 26.2%, with the highest annual hazard rate being in the first year (14.9%). The most frequent DM sites were the skin and soft tissues (SSTs, 32.4%) and distant lymph nodes (LNs, 31.3%). DM sites were categorized into four subgroups of distinct prognosis - distant LN, SST, extracutaneous site, and lymphoma-associated hemophagocytic lymphohistiocytosis. SST or distant LN, solitary metastasis, and late-onset DM demonstrated a relatively favorable prognosis. Contemporary chemotherapy significantly decreased DM rates and improved DMFS. Decreased DM rates were further associated with increased OS probabilities. Our findings improve the understanding of the variable clinical behaviors of early-stage ENKTCL based on four distinct DM sites and thus provide guidance for future therapeutic decisions, metastatic surveillance, and translational trial design.

The HALP (hemoglobin, albumin, lymphocyte, and platelet) score is associated with early-onset post-stroke cognitive impairment.

BACKGROUND: The HALP score (hemoglobin, albumin, lymphocyte, and platelet) is a novel indicator that measures systemic inflammation and nutritional status. The goal of this study was to look into the relationship between the HALP score and post-stroke cognitive impairment (PSCI) in people who had an acute ischemic stroke (AIS). METHODS: A total of 592 individuals with ischemic stroke were included in the research, and the PSCI (n = 382) and non-PSCI (n = 210) groups were determined using the Mini-Mental State Examination scale 2 weeks following the stroke. HALP score was computed by the formula: hemoglobin (g/L) × albumin (g/L) × lymphocytes (/L) / platelets (/L), and was split into three layers according to the tertiles. The connection between the HALP and cognitive results was investigated by binary logistic regression. RESULTS: The PSCI group's HALP score was much lower than the non-PSCI group's (p < 0.001). The HALP score was divided into three layers: T1 ≤ 34.0, T2 34.1-49.4, and T3 ≥ 49.5, respectively. In the binary regression analysis, taking the T3 layer as the reference, the T1 layer showed the highest risk of PSCI after adjusting for confounding factors (odds ratio (OR) = 1.965, 95% confidence interval (CI) = 1.237-3.122, p = 0.004), while there was no increased risk of PSCI in the T2 layer (OR = 1.538, 95%CI = 0.983-2.404, p = 0.059). CONCLUSION: Low HALP score at admission was found to be correlated with early-onset PSCI and may help clinicians in the early identification of high-risk patients.

Association Between the Serum Iron and Acute Cognitive Impairment After Stroke: A Cross-Sectional Study.

BACKGROUND: Complications such as cognitive impairment are common in stroke victims. The goal of this study was to see if there was a link between blood iron levels and post-stroke cognitive impairment (PSCI) within 2 weeks after stroke. METHODS: A total of 313 patients with ischemic stroke were recruited and separated into two groups: PSCI (n = 202) and non-PSCI (n = 111). The Mini-mental state examination scale was used to evaluate the cognitive status within 2 weeks after stroke (acute phase). The serum iron levels were divided into 4 layers: Q1 ≤ 11.7 µmol/L, Q2 11.8-15.1 µmol/, Q3 15.2-19.3 µmol/L, Q4 ≥ 19.4 µmol/L, respectively. The connection between serum iron and PSCI was then investigated further using binary logistic regression, which was adjusted for confounders. RESULTS: The difference in serum iron levels between the PSCI and non-PSCI group was initially conducted by the Mann-Whitney test, and a significant difference was found (14.5 (11.0-17.8) vs. 16.9 (13.7-21.8), p < .001), with no confounders being adjusted. After adjusting for confounding factors, the binary regression analysis showed that the Q4 layer showed the lowest risk of PSCI, with the Q1 layer being the reference. (odds ratio (OR) = 0.297, 95% confidence interval (CI) = 0.136-0.649, p = 0.002). CONCLUSION: A decreased risk of early-onset PSCI was linked to high serum iron levels. Low serum iron levels were found to be a risk factor for acute cognitive impairment following stroke, which could help physicians identify and take intervention measures early to reduce the risk of cognitive impairment after stroke.

Evaluation of the ability of fatty acid metabolism signature to predict response to neoadjuvant chemoradiotherapy and prognosis of patients with locally advanced rectal cancer.

Neoadjuvant chemoradiotherapy (nCRT) is widely used to treat patients with locally advanced rectal cancer (LARC), and treatment responses vary. Fatty acid metabolism (FAM) is closely associated with carcinogenesis and cancer progression. In this study, we investigated the vital role of FAM on the gut microbiome and metabolism in the context of cancer. We screened 34 disease-free survival (DFS)-related, FAM-related, and radiosensitivity-related genes based on the Gene Expression Omnibus database. Subsequently, we developed a five-gene FAM-related signature using the least absolute shrinkage and selection operator Cox regression model. The FAM-related signature was also validated in external validation from Fujian Cancer Hospital for predicting nCRT response, DFS, and overall survival (OS). Notably, patients with a low-risk score were associated with pathological complete response and better DFS and OS outcomes. A comprehensive evaluation of the tumor microenvironment based on the FAM-related signature revealed that patients with high-risk scores were closely associated with activating type I interferon response and inflammation-promoting functions. In conclusion, our findings indicate the potential ability of FAM to predict nCRT response and the prognosis of DFS and OS in patients with LARC.