Perioperative and Post-Hospital Whole-Course nutrition management in patients with pancreatoduodenectomy - a Single-Center prospective randomized controlled trial.

OBJECTIVE: Whole-course nutrition management (WNM) has been proven to improve outcomes and reduce complications. We conducted this randomized controlled trial to validate its effectiveness in patients undergoing pancreatoduodenectomy. METHODS: From December 1, 2020, to November 30, 2023, this single-center randomized clinical trial was conducted at the Department of Hepatobiliopancreatic Surgery in a major hospital in Beijing, China. Participants who were undergoing pancreatoduodenectomy were enrolled and randomly allocated to either the WNM group or the control group. The primary outcome was the incidence of postoperative complications. Subgroup analysis in patients who were at nutritional risk was performed. Finally, a six-month follow-up was conducted and the economic benefit was evaluated using an incremental cost-effectiveness ratio (ICER). RESULTS: A total of 84 patients were randomly assigned (1:1) into the WNM group and the control group. The incidences of total complications (47.6% vs. 69.0%, P=0.046), total infections (14.3% vs. 33.3%, P= 0.040) and abdominal infection (11.9% vs. 31.0%, P= 0.033) were significantly lower in the WNM group. In the subgroup analysis of patients at nutritional risk, 66 cases were included (35 cases in the WNM group and 31 cases in the control group). The rate of abdominal infection (11.4% vs. 32.3%, P= 0.039) and postoperative length of stay (23.1±10.3 vs. 30.4±17.2, P= 0.046) were statistically different between the two subgroups. In the six-month follow-up, more patients reached the energy target in the WNM group (97.0% vs. 79.4%, P=0.049) and got a higher daily energy intake (1761.3±339.5 vs. 1599.6±321.5, P=0.045). The ICER suggested that WNM saved 31,511 Chinese Yuan (CNY) while reducing the rate of total infections by 1% in the ITT population and saved 117,490 CNY in patients at nutritional risk, while WNM saved 31,511 CNY while reducing the rate of abdominal infections by 1% in the ITT population and saved 101,359 CNY in patients at nutritional risk. CONCLUSION: In this trial, whole-course nutrition management was associated with fewer total postoperative complications, total and abdominal infections, and was cost-effective, especially in patients at nutritional risk. It seems to be a favorable strategy for patients undergoing PD.

The cyclic guanosine monophosphate synthase-stimulator of interferon genes pathway as a potential target for tumor immunotherapy.

Cyclic guanosine monophosphate-adenosine monophosphate (cGAMP) synthase (cGAS) detects infections or tissue damage by binding to microbial or self-DNA in the cytoplasm. Upon binding DNA, cGAS produces cGAMP that binds to and activates the adaptor protein stimulator of interferon genes (STING), which then activates the kinases IKK and TBK1 to induce the secretion of interferons and other cytokines. Recently, a series of studies demonstrated that the cGAS-STING pathway, a vital component of host innate immunity, might play an important role in anticancer immunity, though its mechanism remains to be elucidated. In this review, we highlight the latest understanding of the cGAS-STING pathway in tumor development and the advances in combination therapy of STING agonists and immunotherapy.

Combination therapy with PD-1 inhibition plus rapamycin and metformin enhances anti-tumor efficacy in triple negative breast cancer.

Immunotherapy using PD-1/PD-L1 inhibitors has been proved to be effective in triple negative breast cancer (TNBC), albeit only in a fraction of patients. Emerging evidences indicate mTOR blockade and metformin may re-orchestrate the immune system in tumors. Herein, in this study we aimed to evaluate the anti-tumor efficacy of PD-1 monoclonal antibody with mTOR inhibitor rapamycin or with the anti-diabetic drug metformin. The status of PD-1/PD-L1 and mTOR pathway was determined through analyzing the TCGA and CCLE data in TNBCs as well as by detection at mRNA and protein level. The inhibition of tumor growth and metastasis by anti-PD-1 combined with rapamycin or with metformin was evaluated in allograft mouse model of TNBC. The effects of combination therapy on the AMPK, mTOR and PD-1/PD-L1 pathways were also evaluated. The combination treatment with PD-1 McAb and rapamycin/metformin had additive effects on suppression of tumor growth and distant metastasis in mice. Compared with the control group and the monotherapy, combined PD-1 McAb with either rapamycin or metformin exhibited more obvious effects on induction of necrosis, CD8+ T lymphocytes infiltrating and inhibition of PD-L1 expression in TNBC homograft. In vitro study showed either rapamycin or metformin not only decreased PD-L1 expression, but increased p-AMPK expression and therefore led to down-regulation of p-S6. In summary, combination of PD-1 antagonist with either rapamycin or metformin led to more infiltrating TILs and decreased PD-L1 resulting in enhanced antitumor immunity and blockade of PD-1/PD-L1 pathway. Our results suggested such combination therapy may be a potential therapeutic strategy for TNBC patients.

Development of the Scientific, Transparent and Applicable Rankings (STAR) tool for clinical practice guidelines.

BACKGROUND: This study aimed to develop a comprehensive instrument for evaluating and ranking clinical practice guidelines, named Scientific, Transparent and Applicable Rankings tool (STAR), and test its reliability, validity, and usability. METHODS: This study set up a multidisciplinary working group including guideline methodologists, statisticians, journal editors, clinicians, and other experts. Scoping review, Delphi methods, and hierarchical analysis were used to develop the STAR tool. We evaluated the instrument's intrinsic and interrater reliability, content and criterion validity, and usability. RESULTS: STAR contained 39 items grouped into 11 domains. The mean intrinsic reliability of the domains, indicated by Cronbach's α coefficient, was 0.588 (95% confidence interval [CI]: 0.414, 0.762). Interrater reliability as assessed with Cohen's kappa coefficient was 0.774 (95% CI: 0.740, 0.807) for methodological evaluators and 0.618 (95% CI: 0.587, 0.648) for clinical evaluators. The overall content validity index was 0.905. Pearson's r correlation for criterion validity was 0.885 (95% CI: 0.804, 0.932). The mean usability score of the items was 4.6 and the median time spent to evaluate each guideline was 20 min. CONCLUSION: The instrument performed well in terms of reliability, validity, and efficiency, and can be used for comprehensively evaluating and ranking guidelines.

Relationship between preoperative malnutrition, frailty, sarcopenia, body composition, and anthropometry in elderly patients undergoing major pancreatic and biliary surgery.

Objective: To analyze the correlation between preoperative nutritional status, frailty, sarcopenia, body composition, and anthropometry in geriatric inpatients undergoing major pancreatic and biliary surgery. Methods: This is a cross-sectional study of the database from December 2020 to September 2022 in the department of hepatopancreatobiliary surgery, Beijing Hospital. Basal data, anthropometry, and body composition were recorded. NRS 2002, GLIM, FFP 2001, and AWGS 2019 criteria were performed. The incidence, overlap, and correlation of malnutrition, frailty, sarcopenia, and other nutrition-related variables were investigated. Group comparisons were implemented by stratification of age and malignancy. The present study adhered to the STROBE guidelines for cross-sectional study. Results: A total of 140 consecutive cases were included. The prevalence of nutritional risk, malnutrition, frailty, and sarcopenia was 70.0, 67.1, 20.7, and 36.4%, respectively. The overlaps of malnutrition with sarcopenia, malnutrition with frailty, and sarcopenia with frailty were 36.4, 19.3, and 15.0%. There is a positive correlation between every two of the four diagnostic tools, and all six p-values were below 0.002. Albumin, prealbumin, CC, GS, 6MTW, ASMI, and FFMI showed a significantly negative correlation with the diagnoses of the four tools. Participants with frailty or sarcopenia were significantly more likely to suffer from malnutrition than their control groups with a 5.037 and 3.267 times higher risk, respectively (for frailty, 95% CI: 1.715-14.794, p = 0.003 and for sarcopenia, 95% CI: 2.151-4.963, p<0.001). Summarizing from stratification analysis, most body composition and function variables were worsen in the ≥70 years group than in the younger group, and malignant patients tended to experience more intake reduction and weight loss than the benign group, which affected the nutrition diagnosis. Conclusion: Elderly inpatients undergoing major pancreatic and biliary surgery possessed high prevalence and overlap rates of malnutrition, frailty, and sarcopenia. Body composition and function deteriorated obviously with aging.

Development and Assessment of Assisted Diagnosis Models Using Machine Learning for Identifying Elderly Patients With Malnutrition: Cohort Study.

BACKGROUND: Older patients are at an increased risk of malnutrition due to many factors related to poor clinical outcomes. OBJECTIVE: This study aims to develop an assisted diagnosis model using machine learning (ML) for identifying older patients with malnutrition and providing the focus of individualized treatment. METHODS: We reanalyzed a multicenter, observational cohort study including 2660 older patients. Baseline malnutrition was defined using the global leadership initiative on malnutrition (GLIM) criteria, and the study population was randomly divided into a derivation group (2128/2660, 80%) and a validation group (532/2660, 20%). We applied 5 ML algorithms and further explored the relationship between features and the risk of malnutrition by using the Shapley additive explanations visualization method. RESULTS: The proposed ML models were capable to identify older patients with malnutrition. In the external validation cohort, the top 3 models by the area under the receiver operating characteristic curve were light gradient boosting machine (92.1%), extreme gradient boosting (91.9%), and the random forest model (91.5%). Additionally, the analysis of the importance of features revealed that BMI, weight loss, and calf circumference were the strongest predictors to affect GLIM. A BMI of below 21 kg/m2 was associated with a higher risk of GLIM in older people. CONCLUSIONS: We developed ML models for assisting diagnosis of malnutrition based on the GLIM criteria. The cutoff values of laboratory tests generated by Shapley additive explanations could provide references for the identification of malnutrition. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR-EPC-14005253; https://www.chictr.org.cn/showproj.aspx?proj=9542.

Integrated analysis identifies oxidative stress-related lncRNAs associated with progression and prognosis in colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) is one of the most common cancers in the world. Oxidative stress reactions have been reportedly associated with oncogenesis and tumor progression. By analyzing mRNA expression data and clinical information from The Cancer Genome Atlas (TCGA), we aimed to construct an oxidative stress-related long noncoding RNA (lncRNA) risk model and identify oxidative stress-related biomarkers to improve the prognosis and treatment of CRC. RESULTS: Differentially expressed oxidative stress-related genes (DEOSGs) and oxidative stress-related lncRNAs were identified by using bioinformatics tools. An oxidative stress-related lncRNA risk model was constructed based on 9 lncRNAs (AC034213.1, AC008124.1, LINC01836, USP30-AS1, AP003555.1, AC083906.3, AC008494.3, AC009549.1, and AP006621.3) by least absolute shrinkage and selection operator (LASSO) analysis. The patients were then divided into high- and low-risk groups based on the median risk score. The high-risk group had a significantly worse overall survival (OS) (p < 0.001). Receiver operating characteristic (ROC) and calibration curves displayed the favorable predictive performance of the risk model. The nomogram successfully quantified the contribution of each metric to survival, and the concordance index and calibration plots demonstrated its excellent predictive capacity. Notably, different risk subgroups showed significant differences in terms of their metabolic activity, mutation landscape, immune microenvironment and drug sensitivity. Specifically, differences in the immune microenvironment implied that CRC patients in certain subgroups might be more responsive to immune checkpoint inhibitors. CONCLUSIONS: Oxidative stress-related lncRNAs can predict the prognosis of CRC patients, which provides new insight for future immunotherapies based on potential oxidative stress targets.

[Retracted] Metformin exerts anticancer effects through the inhibition of the Sonic hedgehog signaling pathway in breast cancer.

Following the publication of this paper, it was drawn to the Editor's attention by concerned readers that several of the cellular images shown in Figs. 6A and 8A, the scratch­wound assay images shown in Fig. 5A, the western blotting data in Figs. 2C and 7A and the Matrigel invasion assays in Fig. 5C were strikingly similar to data appearing in different form in other articles by different authors. Owing to the fact that the contentious data in the above article had already been published elsewhere, or were already under consideration for publication, prior to its submission to International Journal of Molecular Medicine, the Editor has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused. [International Journal of Molecular Medicine 36: 204­214, 2015; DOI: 10.3892/ijmm.2015.2217].

Predictive value of the presence of Prevotella and the ratio of Porphyromonas gingivalis to Prevotella in saliva for esophageal squamous cell carcinoma.

Background: Imbalance of oral salivary microbiota has been linked to the pathogenesis of a variety of systemic diseases, and oral bacterial species have been shown to be useful biomarkers for systemic diseases.This study aimed to characterize the alterations of oral microbiota in patients with esophageal squamous cell carcinoma (ESCC) and to evaluate the diagnostic performance of oral microbial biomarkers for ESCC. Methods: The relative abundance of flora in saliva samples was analyzed by 16S rDNA sequencing, and differences in the species present in samples from ESCC patients and healthy controls (HCs) were identified by analyzing species diversity and performing LEfSe analysis. Receiver operating characteristic (ROC) curve analysis was applied to evaluate the diagnostic performance of the characteristic bacteria individually and in combination. Results: Differences in bacterial diversity indexes were observed for the saliva of ESCC patients versus HCs (P<0.05), but principal coordinate analysis did not detect a significant difference in the composition of oral microbiota between ESCC patients and HCs (P>0.05). LEfSe analysis showed that Leptotrichia, Porphyromonas (Pg), Streptococcus, Rothia, Lactobacillus and Peptostreptococcus were more abundant in ESCC patient saliva than in HC saliva, whereas Haemophilus, Alloprevotella (All), Prevotella_7, Prevotella (Pre), Prevotella_6, Pasteurellaceae and Pasteurellales were significantly less abundant in ESCC patient saliva (P<0.05). From ROC curve analysis, Pg could detect ESCC with an area under the ROC curve (AUC) of 0.599, sensitivity of 62.2%, and specificity of 70%, whereas the ratio of Pg/Pre had an AUC of 0.791, sensitivity of 93.3%, and specificity of 62.3%. Moreover, the combination of the Pg/Pre and Pg/All ratios showed further improved diagnostic performance for ESCC (AUC=0.826) and even good sensitivity and specificity for the diagnosis of early ESCC (68.2% and 86%, respectively; AUC=0.786). Conclusion: This study shows that Pg in saliva can be used as a characteristic marker of ESCC, and the ratios of Pg/Pre and Pg/All offered significantly improved diagnostic performance, especially for early ESCC.

Malnutrition dynamics according to GLIM criteria in hospitalized elderly.

BACKGROUND AND OBJECTIVES: Assess the different nutritional status between admission and discharged in older adult patients using the GLIM criteria. METHODS AND STUDY DESIGN: A retrospective analysis was conducted on a multicenter study which initiated in 34 hospitals in China with 2734 hospitalized older patients. The dynamic changes of malnutrition according to GLIM criteria were performed between at admission and discharge, and their significance was analyzed using the chi-square test. The association between malnutrition and clinical outcomes was analyzed using the chi-square test, t-test, or rank sum test, and divided into different disease types for further analysis. RESULTS: The incidence of nutritional risk in elderly patients was 51.6% at admission and 48.4% at discharge. The prevalence of malnutrition according to the GLIM criteria was 19.6% at admission and increased to 33.4% at discharge, which was significantly different. Different age and disease type were related with nutrition status. Malnutrition is significantly association with adverse clinical outcomes such as increased risk of complications and prolonged length of hospital stay. CONCLUSIONS: The GLIM criteria can be used in elderly patients to assess malnutrition. The prevalence of malnutrition in elderly inpatients is high, and the prevalence of malnutrition at discharge is higher than that observed at admission. Attention should be paid to the dynamic changes of malnutrition in elderly patients during hospitalization.

Preoperative Anemia Is a Predictor of Worse Postoperative Outcomes Following Open Pancreatoduodenectomy: A Propensity Score-Based Analysis.

Background: Preoperative anemia is a common clinical situation proved to be associated with severe outcomes in major surgeries, but not in pancreatic surgery. We aim to study the impact of preoperative anemia on morbidity and mortality in patients undergoing open pancreatoduodenectomy and use propensity score matching (PSM) to balance the basal data and reduce bias. Methods: We analyzed the data of consecutive patients undergoing open pancreatoduodenectomy with a complete record of preoperative hemoglobin, at two pancreatic centers in China between 2015 and 2019. Anemia is defined as hemoglobin less than 12 g/dl for male and 11 g/dl for female, following Chinese criteria. We compared clinical and economic outcomes before and after PSM and used logistic regression analysis to assess the correlation between variables and anemia. Results: The unmatched initial cohort consisted of 517 patients. A total of 148 cases (28.6%) were diagnosed with anemia at admission, and no case received a preoperative blood transfusion or anti-anemia therapy. After PSM, there were 126 cases in each group. The rate of severe postoperative complications was significantly higher in the anemia group than in the normal group (43.7% vs. 27.0%, p = 0.006), among which the differences in prevalence of clinically relevant postoperative pancreatic fistula (CR-POPF) (31.0% vs. 15.9%, p = 0.005) and cardiac and cerebrovascular events (4.0% vs. 0.0%, p = 0.024) were the most significant. The costs involved were more in the anemia group (26958.2 ± 21671.9 vs. 20987.7 ± 10237.9 USD, p = 0.013). Among anemic patients, receiver operating characteristic (ROC) curve analysis shows the cut-off value of hemoglobin, below which, patients are prone to suffer from major complications (104.5 g/l in male and 90.5 g/l in female). Among all patients, multivariate analysis showed that preoperative obstructive jaundice [odds ratio (OR) = 1.813, 95% confidence interval (CI) (1.206-2.725), p = 0.004] and pancreatic ductal adenocarcinoma [OR = 1.861, 95% CI (1.178-2.939), p = 0.008] were predictors of anemia. Among paired patients, preoperative anemia [OR = 2.593, 95% CI (1.481-5.541), p = 0.001] and malignant pathology [OR = 4.266, 95% CI (1.597-11.395), p = 0.004] were predictors of postoperative severe complications. Conclusion: Preoperative anemia is a predictor of worse postoperative outcomes following open pancreatoduodenectomy and needs to be identified and treated.

Salivary microbiota may predict the presence of esophageal squamous cell carcinoma.

The aim is to explore the predictive value of salivary bacteria for the presence of esophageal squamous cell carcinoma (ESCC). Saliva samples were obtained from 178 patients with ESCC and 101 healthy controls, and allocated to screening and verification cohorts, respectively. In the screening phase, after saliva DNA was extracted, 16S rRNA V4 regions of salivary bacteria were amplified by polymerase chain reaction (PCR) with high-throughput sequencing. Highly expressed target bacteria were screened by Operational Taxonomic Units clustering, species annotation and microbial diversity assessment. In the verification phase, the expression levels of target bacteria identified in the screening phase were verified by absolute quantitative PCR (Q-PCR). Receiver operating characteristic (ROC) curves were plotted to investigate the predictive value of target salivary bacteria. LEfSe analysis revealed higher proportions of Fusobacterium, Streptococcus and Porphyromonas, and Q-PCR assay showed significantly higher numbers of Streptococcus salivarius, Fusobacterium nucleatum and Porphyromonas gingivalis in patients with ESCC, when compared with healthy controls (all P < 0.05). The areas under the ROC curves for Streptococcus salivarius, Fusobacterium nucleatum, Porphyromonas gingivalis and the combination of the three bacteria for predicting patients with ESCC were 69%, 56.5%, 61.8% and 76.4%, respectively. The sensitivities corresponding to cutoff value were 69.3%, 22.7%, 35.2% and 86.4%, respectively, and the matched specificity were 78.4%, 96.1%, 90.2% and 58.8%, respectively. These highly expressed Streptococcus salivarius, Fusobacterium nucleatum and Porphyromonas gingivalis in the saliva, alone or in combination, indicate their predictive value for ESCC.

Acidic Tumor Microenvironment Promotes Pancreatic Cancer through miR-451a/MEF2D Axis.

Pancreatic cancer (PC), as a highly malignant and aggressive solid tumor, is common in the digestive system. The acidic microenvironment is one of the critical markers of cancer. Nonetheless, there are few studies on how the acidic microenvironment affects the development of PC. This study focused on investigating the specific molecular mechanisms of the acidic microenvironment in PC. In our study, qRT-PCR was conducted for examining microRNA (miR)-451a and myocyte enhancer factor 2D (MEF2D) expressions in PANC-1 cells. Then, detailed functional effects of an acidic environment on miR-451a and MEF2D in PANC-1 cells were detected by CCK-8, colony formation, flow cytometry, wound healing, transwell, mitochondrial functionality measurement, JC-1 staining, DCFH-DA staining, and sphere formation assays. The relationship between miR-451a and MEF2D was confirmed by luciferase reporter analysis. Under acidic conditions, the increase of proliferation, migration, and invasion of PANC-1 cells was observed. Moreover, the mitochondrial oxidative respiration-related gene miR-451a was reduced in acidic conditions. In addition, we found that, in PANC-1 cells under an acidic environment, miR-451a overexpression enhanced oxygen consumption, mitochondrial membrane potential (MMP) loss, and ROS generation and inhibited proliferation, migration, invasion, and stemness via sponging MEF2D. In a word, our results revealed that the acidic microenvironment regulated PC progression by affecting the miR-451a/MEF2D axis, indicating a novel avenue for the future treatment of PC.

Modification of a new subclassification of Grade B postoperative pancreatic fistula: A bicenter retrospective cohort study.

AIM: To propose a modified subclassification of grade B postoperative pancreatic fistula (POPF) based on management approaches in Chinese patients. METHODS: Data of consecutive pancreatoduodenectomy at two hospitals in China from 2013 to 2018 were collected, and outcomes were compared across different groups of POPF. Subclassification of B-POPF was made based on intervention to B1: non-interventional subclass and B2: interventional subclass. RESULTS: A total of 142 of 522 patients had biochemical leaks (BLs) (27.2%), and POPFs developed in 106 of 522 patients (20.3%), with 81 B-POPFs (15.5%) and 25 C-POPFs (4.8%). BL did not differ from the non-fistula condition in almost all outcomes. The differences of outcomes among the non-fistula/BL, B-POPF and C-POPF groups were significant. The prevalence of subclass B1 and B2 was 56.8% (46/81) and 43.2% (35/81), respectively. Compared to the B1 group, patients in the B2 group had worse outcomes, such as post-pancreatectomy hemorrhage (15.2% vs 34.3%, P = .045), biliary fistula (13.0% vs 34.3%, P = .023), postoperative hospital stay (32 vs 39 days, P = .011), and cost ($US28 601.0 vs $US39 314.5, P < .001). CONCLUSION: The recently reported B-POPF subclassification method was modified in Chinese patients according to the intervention, and is more practical, simpler and fits Chinese patients.

Establishing a new body mass index cutoff value for malnutrition diagnosis using the Global Leadership Initiative on Malnutrition (GLIM) tool in Chinese older adults.

BACKGROUND: The body weight of the Chinese population rose rapidly over the past two decades. The old 2001 body mass index (BMI) cutoff value for malnutrition may underestimate malnutrition diagnosis. We explored the BMI cutoff value for malnutrition diagnosis based on national BMI data from the past 30 years and applied it to the Global Leadership Initiative on Malnutrition (GLIM) criteria when investigating malnutrition in hospitalized older patients. METHODS: To explore the BMI cutoff value for malnutrition, we established a linear stepwise model to predict the annual increasing BMI trend based on data from the national BMI data set. The new cutoff value was applied to a large-scale data set from a cross-sectional study pertaining to older hospitalized patients recruited from 30 large hospitals in China. RESULTS: The BMI increased from 21.8 to 23 kg/m2 in two decades. We calculated that the net BMI increase will be 1.49 kg/m2 from 1999 to 2019. We subsequently proposed that the BMI cutoff value for malnutrition should rise to 20 kg/m2 . This cutoff value was applied to the validation data set, containing 8725 patients, and the GLIM-determined malnutrition rate was 24.58% (using the Nutrition Risk Screening 2002 [NRS-2002]) and 23.32% (using the Mini Nutritional Assessment-Short Form [MNA-SF]). The results significantly differed from those obtained using the 2001 Chinese BMI criteria. CONCLUSION: The GLIM tool has good applicability in Asian populations, especially in Chinese older patients. The BMI cutoff value for malnutrition should be adjusted to 20 kg/m2 for Chinese adults.

Protein modifications throughout the lung cancer proteome unravel the cancer-specific regulation of glycolysis.

Glycolytic reprogramming is a typical feature of cancer. However, the cancer-specific modulation of glycolytic enzymes requires systematic elucidation. Here, we report a range of dysregulated modifications in association with a family of enzymes specifically related to the glycolysis pathway by systematic identification of delta masses at the proteomic scale in human non-small-cell lung cancer. The most significant modification is the delta mass of 79.967 Da at serine 58 (Ser58) of triosephosphate isomerase (TPI), which is confirmed to be phosphorylation. Blocking TPI Ser58 phosphorylation dramatically inhibits glycolysis, cancer growth, and metastasis. The protein kinase PRKACA directly phosphorylates TPI Ser58, thereby enhancing TPI enzymatic activity and glycolysis. The upregulation of TPI Ser58 phosphorylation is detected in various human tumor specimens and correlates with poor survival. Therefore, our study identifies a number of cancer-specific protein modifications spanned on glycolytic enzymes and unravels the significance of TPI Ser58 phosphorylation in glycolysis and lung cancer development.

Controlling Nutritional Status Score as a Predictive Marker of In-hospital Mortality in Older Adult Patients.

The controlling nutritional status (CONUT) score assesses nutritional status and is associated with short- and long-term prognoses in some diseases, but the significance of the CONUT score for the prediction of in-hospital mortality in older adults is unknown. The purpose was to determine the importance of the CONUT score for the prediction of in-hospital mortality, short-term complications, length of hospital stay, and hospital costs in older adults. Our retrospective cohort study analyzed data from 11,795 older adult patients from two multicenter cohort studies. We performed receiver operating characteristic curve analysis using in-hospital mortality as the endpoint and determined the appropriate CONUT score cut-off by the Youden index. The patients were divided into two high and low groups according to the CONUT cut-off value, and the differences in clinical characteristics and in-hospital clinical outcomes between the two groups were compared. We compared the accuracy of the CONUT score and other nutrition-related tools in predicting in-hospital mortality by calculating the area under the receiver operating characteristic curve and performed univariate and multivariate analyses of predictors of in-hospital mortality. Among all the patients, 178 (1.5%) patients experienced in-hospital death. The optimal cut-off values was 5.5 for the CONUT score. The high CONUT group had a higher incidence of short-term complications and prolonged hospital stay than the low CONUT group (CONUT score <6), but hospital costs were not significantly higher. The CONUT score had the highest predictive ability for in-hospital mortality among the five nutrition-related parameters compared. Multivariate analysis showed that a high CONUT score (CONUT score ≥ 6) was an independent predictor of in-hospital mortality. In conclusion, the present study demonstrated that the CONUT score could be used to predict in-hospital mortality in older adults.

Preoperative Nutrition Support May Reduce the Prevalence of Postoperative Pancreatic Fistula after Open Pancreaticoduodenectomy in Patients with High Nutritional Risk Determined by NRS2002.

BACKGROUND: Clinically relevant postoperative pancreatic fistula (CR-POPF) is a severe complication which may be caused by a perioperative nutrition problem. We aimed to study whether patients with high nutritional risk (NRS2002 score ≥ 5) might benefit from preoperative nutrition support regarding the risk of CR-POPF after open pancreaticoduodenectomy. METHODS: Consecutive patients undergoing open pancreaticoduodenectomy with complete record of NRS2002 at two Chinese institutions between 2013 and 2018 were analysed. CR-POPF was diagnosed following the 2016 ISGPS criteria. Nutrition support included oral nutrition supplement and enteral and parenteral nutrition. Clinical and economic outcomes were analysed. RESULTS: 522 cases were included. 135 cases (25.9%) were at high nutritional risk (NRS2002 score ≥ 5), among which 41 cases (30.4%) received preoperative nutrition support. The CR-POPF rate was significantly lower in the preoperative nutrition support group compared with the no nutrition support group (12.2% versus 28.7%, P = 0.038). Multivariate analysis showed that preoperative nutrition support was a protective factor for CR-POPF in patients at high risk [OR 0.339, 95% CI (0.115-0.965), P = 0.039]. Higher albumin and a larger diameter of the main pancreatic duct were found to be other protectors for CR-POPF. CONCLUSIONS: Patients with high nutritional risk (NRS2002 score ≥ 5) may profit from preoperative nutritional support manifested in the reduction of CR-POPF.

Total Psoas Area Index is Valuable to Assess Sarcopenia, Sarcopenic Overweight/Obesity and Predict Outcomes in Patients Undergoing Open Pancreatoduodenectomy.

BACKGROUND AND AIM: Sarcopenia has been proven to be a risk factor after pancreatoduodenectomy (PD). We aimed to evaluate if decreased psoas muscle area and density shown in CT scan, as measures for sarcopenia, were associated with postoperative major complications and adverse outcomes in patients who underwent PD. PATIENTS AND METHODS: We analyzed 152 consecutive patients who underwent open PD. Total psoas area and muscle attenuation were measured on CT images at the level of the third lumbar vertebra. Total psoas area index (TPAI) was calculated, the cut-off values of TPAI were estimated and validated. The relationship between radiographic characters and outcomes was analyzed. RESULTS: The optimal cut-off values of TPAI were 4.78 cm2/m2 for males and 3.46 cm2/m2 for females. The values were validated by outcomes with significant differences in the rate of major complications, re-operation, length of stay, and total cost. The prevalence of TPAI-defined sarcopenia and sarcopenic overweight/obesity was 38.8% and 17.1% in total. In multivariate logistic regression, rate of major complications was associated with TPAI [OR=0.605, 95% CI (0.414, 0.883), P=0.009], TPAI-defined sarcopenia [OR=8.256, 95% CI (2.890, 23.583), P=0.000] and sarcopenic overweight/obesity [OR=7.462, 95% CI (2.084, 26.724), P=0.002]; meanwhile, NRS2002-defined nutritional risk and GLIM-defined malnutrition did not show relationship with major complications. CONCLUSION: Both sarcopenia and sarcopenic overweight/obesity determined by new TPAI cut-off values were associated with a higher rate of major complications and adverse outcomes in Chinese patients undergoing open PD whereas usual nutritional assessment was not.