Comparison of the cachexia index based on hand-grip strength (H-CXI) with the original CXI for the prediction of cancer cachexia and prognosis in patients who underwent radical colectomy for colorectal cancer.

Background and aims: The cachexia index (CXI) is a novel biomarker for estimating cancer cachexia. The cachexia index based on hand-grip strength (H-CXI) has been recently developed as a simple proxy for CXI. The present study aims to compare both the H-CXI and CXI for the prediction of cancer cachexia and postoperative outcomes in patients who underwent radical colectomy for colorectal cancer. Methods: Patients who underwent radical operations for colorectal cancer were included in this study. Cancer cachexia was diagnosed according to the international consensus outlined by Fearon et al. The cachexia index (CXI) was calculated as [skeletal muscle index (SMI) × serum albumin/neutrophil-to-lymphocyte ratio (NLR)]. The H-CXI was calculated as [hand-grip strength (HGS)/height2 × serum albumin/NLR]. The SMI was measured based on the preoperative CT images at the third lumbar vertebra (L3) level. HGS was measured before surgery. Results: From July 2014 to May 2021, a total of 1,411 patients were included in the present study, of whom 361 (25.6%) were identified as having cancer cachexia. Patients with cachexia had a lower CXI (p < 0.001) and lower H-CXI (p < 0.001) than those without cachexia. A low CXI but not low H-CXI independently predicted cancer cachexia in the multivariate analysis (OR 1.448, p = 0.024). Both a low CXI (HR 1.476, p < 0.001 for OS; HR 1.611, p < 0.001 for DFS) and low H-CXI (HR 1.369, p = 0.007 for OS; HR 1.642, p < 0.001 for DFS) were independent predictors for overall survival (OS) and disease-free survival (DFS) after adjusting for the same covariates. A low H-CXI but not low CXI was an independent risk factor for postoperative complications (OR 1.337, p = 0.044). No significant association was found between cancer cachexia and postoperative complications. Conclusion: The CXI and H-CXI exhibited better prognostic value than cancer cachexia for the prediction of postoperative outcomes in patients who underwent radical colectomy for colorectal cancer. The H-CXI was a superior index over the CXI in predicting short-term clinical outcomes, whereas the CXI demonstrated a closer correlation with Fearon's criteria for cancer cachexia. Ideal tools for the assessment of cancer cachexia should incorporate not only weight loss but also muscle mass, physical function, and inflammatory state.

Prognostic value of GLIM-defined malnutrition in combination with hand-grip strength or gait speed for the prediction of postoperative outcomes in gastric cancer patients with cachexia.

BACKGROUND: Cancer cachexia is associated with impaired functional and nutritional status and worse clinical outcomes. Global Leadership Initiative in Malnutrition (GLIM) consensus recommended the application of GLIM criteria to diagnose malnutrition in patients with cachexia. However, few previous study has applied the GLIM criteria in patients with cancer cachexia. METHODS: From July 2014 to May 2019, patients who were diagnosed with cancer cachexia and underwent radical gastrectomy for gastric cancer were included in this study. Malnutrition was diagnosed using the GLIM criteria. Skeletal muscle index was measured using abdominal computed tomography (CT) images at the third lumbar vertebra (L3) level. Hand-grip strength and 6-meters gait speed were measured before surgery. RESULTS: A total of 356 patients with cancer cachexia were included in the present study, in which 269 (75.56%) were identified as having malnutrition based on the GLIM criteria. GLIM-defined malnutrition alone did not show significant association with short-term postoperative outcomes, including complications, costs or length of postoperative hospital stays. The combination of low hand-grip strength or low gait speed with GLIM-defined malnutrition led to a significant predictive value for these outcomes. Moreover, low hand-grip strength plus GLIM-defined malnutrition was independently associated with postoperative complications (OR 1.912, 95% CI 1.151-3.178, P = 0.012). GLIM-defined malnutrition was an independent predictive factor for worse OS (HR 2.310, 95% CI 1.421-3.754, P = 0.001) and DFS (HR 1.815, 95% CI 1.186-2.779, P = 0.006) after surgery. The addition of low hand-grip strength or low gait speed to GLIM-defined malnutrition did not increase its predictive value for survival. CONCLUSION: GLIM-defined malnutrition predicted worse long-term survival in gastric cancer patients with cachexia. Gait speed and hand-grip strength added prognostic value to GLIM-defined malnutrition for the prediction of short-term postoperative outcomes, which could be incorporated into preoperative assessment protocols in patients with cancer cachexia.

Sarcopenia predicts postoperative complications and survival in colorectal cancer patients with GLIM-defined malnutrition: Analysis from a prospective cohort study.

OBJECTIVE: To investigate whether sarcopenia could predict postoperative outcomes in patients with colorectal cancer with Global Leadership Initiative on Malnutrition (GLIM)-defined malnutrition. METHODS: Clinical data of patients who underwent radical resection for colorectal cancer were prospectively collected. Sarcopenia was diagnosed by the combination of low handgrip strength and low muscle quantity or quality as measured by abdominal computed tomography (CT) images. Logistic regression analysis and Cox proportional hazards regression analysis were performed to identify independent predictors for postoperative complications and survival, respectively. RESULTS: A total of 310 patients with colorectal cancer with GLIM-defined malnutrition were included, of which 145 (46.77%) were identified with sarcopenia. Malnutritional patients with sarcopenia had significantly higher incidences of total complications (34.5% versus 15.8%), severe complications (9.7% versus 1.8%), longer lengths of postoperative hospital stay (median, 14 days versus 12 days), and more costs (median, 56,257 RMB versus 49,024 RMB) than those without sarcopenia. Sarcopenia was an independent predictive factor for postoperative complications (OR 2.531, 95% CI 1.451-4.415), overall survival (HR 1.519, 95% CI 1.026-2.248), and disease-free survival (HR 1.847, 95% CI 1.324-2.576). Patients with severe sarcopenia had a higher incidence of severe complications but not total complications or survival than those with not-severe sarcopenia. Moreover, the predictive value of sarcopenia for postoperative complications was attributed to muscle strength and quality but not muscle quantity. CONCLUSION: Sarcopenia predicts postoperative complications and survival in patients with colorectal cancer with GLIM-defined malnutrition. Preoperative assessment of sarcopenia is still necessary when nutritional assessment has been well performed.

High albumin-bilirubin grade predicts worse short-term complications in gastric cancer patients with metabolic syndrome: a retrospective study.

Background: Preoperative albumin-bilirubin (ALBI) grade has been proposed and applied in recent years to evaluate the prognosis of liver cancer, but its role in gastric cancer (GC) is still unclear. This research aimed to examine the prognostic value of ALBI grade after gastrectomy among patients with GC complicated with metabolic syndrome (MetS). Methods: There were 628 patients who received radical resection for GC. Laboratory data and short-term results were collected prospectively, and preoperative ALBI grades were calculated from the albumin and bilirubin levels. The appropriate ALBI cutoff value was calculated by receiver operating characteristic (ROC) curve analysis, which we used to put patients into high (>-2.54) and low (≤-2.54) ALBI grade groups. The differences between the short-term complication rates of the two groups were analyzed with the chi-square test. Results: Of the included patients, 133 (21.2%) and 495 (78.8%) had high and low ALBI grades, respectively. A high ALBI grade (P=0.001), body mass index (BMI) ≥25 kg/m2 (P=0.001), and hypertension (P=0.018) were independent risk factors for postoperative complications. In GC patients with and without MetS, the high ALBI subgroup showed more overall complications than the low ALBI subgroup (P=0.028 and P=0.001). Among GC patients with MetS, those with a high ALBI grade showed a higher incidence of serious complications than those with a low ALBI grade (P=0.001); a similar, nonsignificant trend occurred in non-MetS patients (P=0.153). Conclusions: The preoperative ALBI grade is important in the prognosis of GC patients with MetS after gastrectomy. GC patients with MetS can lower their incidence of serious complications by adjusting their preoperative ALBI grade.

Global leadership initiative in malnutrition (GLIM) criteria using hand-grip strength adequately predicts postoperative complications and long-term survival in patients underwent radical gastrectomy for gastric cancer.

BACKGROUND: The present study aims to investigate whether malnutrition defined by the Global Leadership Initiative in Malnutrition (GLIM) criteria using hand-grip strength (HGS) adequately predict postoperative complications and long-term survival in patients underwent radical gastrectomy for gastric cancer in a similar manner to GLIM-defined malnutrition using skeletal muscle index (SMI). METHODS: Patients who underwent radical gastrectomy for gastric cancer from August 2014 to June 2019 were included in this study. Clinical data were prospectively collected. Malnutrition was diagnosed based on the two-step approach following the GLIM criteria. Skeletal muscle mass was assessed using SMI based on abdominal computed tomography (CT) scans, or assessed using HGS. RESULTS: A total of 1359 patients were included in this study, in which 36.2% of the patients were at risk of malnutrition (Nutritional Risk Screening 2002 scores ≥3). The incidence of malnutrition was 28.2% and 27.5% using SMI and HGS, respectively. There was a high agreement between the two criteria of malnutrition (kappa = 0.863, P < 0.001). Both of the two criteria of malnutrition were independently associated with postoperative complications (SMI-GLIM, P = 0.041; HGS-GLIM, P = 0.023), overall survival (P < 0.001, both), and disease-free survival (P < 0.001, both), with similar odds ratio or hazard ratio after adjusting for the same confounding variables. HGS-GLIM malnutrition (P = 0.046) but not SMI-GLIM malnutrition (P = 0.270) was associated with a higher incidence of severe complications. CONCLUSIONS: GLIM criteria using HGS is a useful tool to diagnose malnutrition and has a similar or even better predictive value for postoperative complications and long-term survival after radical gastrectomy for gastric cancer compared with GLIM criteria using SMI.

Effect of GLIM-defined malnutrition on postoperative clinical outcomes in patients with colorectal cancer.

BACKGROUND: Malnutrition is common in colorectal cancer patients. Malnutrition is recognized as a risk factor for adverse postoperative outcomes, yet there are no consistent diagnostic criteria for it. Thus, the Global Leadership Initiative on Malnutrition published new universal criteria. We aimed to investigate the prevalence of malnutrition with the application of Global Leadership Initiative on Malnutrition criteria, and explore the correlations between Global Leadership Initiative on Malnutrition-defined malnutrition and postoperative clinical outcomes in colorectal cancer patients. METHODS: We included a cohort of 918 patients who underwent radical resection surgery for colorectal cancer from July 2014 to October 2019. Malnutrition was diagnosed based on the Global Leadership Initiative on Malnutrition criteria. The associations between nutritional status and postoperative clinical outcomes were analyzed by the Kaplan-Meier method, logistic and Cox regression analyses. RESULTS: Among the included patients, 23.6% were diagnosed as malnutrition based on Global Leadership Initiative on Malnutrition criteria. Global Leadership Initiative on Malnutrition-defined malnutrition was associated with total postoperative complications [odds ratio: 1.497 (1.042-2.152), P = 0.029]. Further, Global Leadership Initiative on Malnutrition-diagnosed malnutrition was an independent risk factor for overall survival [hazard ratio: 1.647 (1.048-2.587), P = 0.030] and disease-free survival [hazard ratio: 1.690 (1.169-2.441), P = 0.005]. CONCLUSIONS: The Global Leadership Initiative on Malnutrition criteria is effective to assess malnutrition. Preoperative malnutrition is associated with postoperative complications, overall survival and disease-free survival in colorectal cancer patients after radical resection surgery.

Inflammation Disturbed the Tryptophan Catabolites in Hippocampus of Post-operative Fatigue Syndrome Rats via Indoleamine 2,3-Dioxygenas Enzyme and the Improvement Effect of Ginsenoside Rb1.

AIM: Post-operative fatigue syndrome (POFS) is a common complication that prolongs the recovery to normal function and activity after surgery. The aim of the present study was to explore the mechanism of central fatigue in POFS and the anti-fatigue effect of ginsenoside Rb1. METHOD: We investigated the association between inflammation, indoleamine 2,3-dioxygenase (IDO) enzyme, and tryptophan metabolism in the hippocampus of POFS rats. A POFS rat model was induced by major small intestinal resection. Rats with major small intestinal resection were administered ginsenoside Rb1 (15 mg/kg) once a day from 3 days before surgery to the day of sacrifice, or with saline as corresponding controls. Fatigue was assessed with the open field test (OFT) and sucrose preference test (SPT). ELISA, RT-PCR, Western blot, immunofluorescence, and high-performance liquid chromatography (HPLC) were used to test the inflammatory cytokines; p38MAPK, NF-κB/p65, and IDO enzyme expressions; and the concentrations of tryptophan, kynurenine, and serotonin, respectively. RESULT: Our results showed that POFS was associated with increased expressions of inflammatory cytokines and p38MAPK and higher concentrations of kynurenine and tryptophan on post-operative days 1 and 3; a lower serotonin level on post-operative day 1; and an enhanced translocation of NF-κB/p65 and the IDO enzyme on post-operative days 1, 3, and 5. Ginsenoside Rb1 had an improvement effect on these. CONCLUSION: Inflammatory cytokines induced by large abdominal surgery disturb tryptophan metabolism to cause POFS through the activation of the p38MAPK-NF-κB/p65-IDO pathway in the hippocampus. Ginsenoside Rb1 had an anti-fatigue effect on POFS by reducing inflammation and IDO enzyme.

Spinal Nrf2 translocation may inhibit neuronal NF-κB activation and alleviate allodynia in a rat model of bone cancer pain.

Bone cancer pain (BCP) is a clinical pathology that urgently needs to be solved, but research on the mechanism of BCP has so far achieved limited success. Nuclear factor erythroid 2 (NFE2)-related factor 2 (Nrf2) has been shown to be involved in pain, but its involvement in BCP and the specific mechanism have yet to be examined. This study aimed to test the hypothesis that BCP induces the transfer of Nrf2 from the cytoplasm to the nucleus and further promotes nuclear transcription to activate heme oxygenase-1 (HO-1) and inhibit the activation of nuclear factor-kappa B (NF-κB) signalling, ultimately regulating the neuroinflammatory response. Von-Frey was used for behavioural analysis in rats with BCP, whereas western blotting, real-time quantitative PCR (RT-PCR) and enzyme-linked immunosorbent assay (ELISA) were used to detect molecular expression changes, and immunofluorescence was used to detect cellular localization. We demonstrated that BCP induced increased Nrf2 nuclear protein expression with decreased cytoplasmic protein expression in the spinal cord. Further increases in Nrf2 nuclear protein expression can alleviate hyperalgesia and activate HO-1 to inhibit the expression of NF-κB nuclear protein and inflammatory factors. Strikingly, intrathecal administration of the corresponding siRNA reversed the above effects. In addition, the results of double immune labelling revealed that Nrf2 and NF-κB were coexpressed in spinal cord neurons of rats with BCP. In summary, these findings suggest that the entry of Nrf2 into the nucleus promotes the expression of HO-1, inhibiting activation of the NF-κB signalling pathway, reducing neuroinflammation and ultimately exerting an anti-nociceptive effect.

Effect of suspension training on neuromuscular function, postural control, and knee kinematics in anterior cruciate ligament reconstruction patients.

BACKGROUND: Suspension training (SET) is a method of neuromuscular training that enables the body to carry out active training under unstable support through a suspension therapy system. However, there have been few reports in the literature on the application of SET to anterior cruciate ligament reconstruction (ACLR) patients. It is not clear what aspects of the patient's function are improved after SET. AIM: To investigate the effect of SET on the neuromuscular function, postural control, and knee kinematics of patients after ACLR surgery. METHODS: Forty participants were randomized to an SET group or a control group. The SET group subjects participated in a SET protocol over 6 wk. The control group subjects participated in a traditional training protocol over 6 wk. Isokinetic muscle strength of the quadriceps and hamstrings, static and dynamic posture stability test, and relative translation of the injured knee were assessed before and after training. RESULTS: The relative peak torque of the quadriceps and hamstrings in both groups increased significantly (P < 0.001), and the SET group increased by a higher percentage than those in the control group (quadriceps: P = 0.004; hamstrings: P = 0.011). After training, both groups showed significant improvements in static and dynamic posture stability (P < 0.01), and the SET group had a greater change than the control group (P < 0.05). No significant improvement on the relative translation of the injured knee was observed after training in either group (P > 0.05). CONCLUSION: Our findings show that SET promotes great responses in quadriceps and hamstring muscle strength and balance function in ACLR patients.

Evaluation of Clinical Graded Treatment of Acute Nonsuppurative Otitis Media in Children with Acute Upper Respiratory Tract Infection.

Objective: To treat children with acute nonsuppurative otitis media induced by acute upper respiratory tract infection of varying severity and evaluate its therapeutic effects. Materials and Methods: Patients from the emergency department with acute nonsuppurative otitis media were followed up between September 2015 and December 2018. A total of 420 patients were classified into grades I to III according to tympanic membrane intactness and systemic reactions and treated according to grading. Results: Grade I patients showed no significant difference in the recovery of acute symptoms whether antibiotics are used or not. Grade II patients, after 3 months of follow-up, showed no tympanic membrane perforation, and 9 cases of binaural B-type children did not improve but were cured by operation. In grade III patients, after treatment for 4 hours in the experimental group 3, the earache subsided, 1 case had tympanic membrane perforation, and the patients recovered after 2 weeks (64/92) and after 3 months (28/92) of drug treatment. After treatment for 4 h in the control group 3, the earache eased, and 3 patients developed tympanic membrane perforation and were treated for 3 months. 4 binaural B-type children did not improve but recovered after surgical treatment. Conclusion: Grade I patients could be closely followed up by clinical observation. For anti-inflammatory patients with grade II disease, treatment has therapeutic significance. For patients with grade III, some patients still have TMP, but the use of cephalosporin third-generation drugs plus an appropriate amount of hormone therapy is effective in reducing symptoms and tympanic local reactions.

The relationship between the GLIM-defined malnutrition, body composition and functional parameters, and clinical outcomes in elderly patients undergoing radical gastrectomy for gastric cancer.

OBJECTIVE: The present study aims to determine the correlations between Global Leadership Initiative in Malnutrition (GLIM)-defined malnutrition and body composition and functional parameters, and to comprehensively analyze the predictive value of GLIM-defined malnutrition for postoperative outcomes in the context of detailed measurement of body composition and functional parameters in elderly patients who underwent radical gastrectomy for gastric cancer. METHODS: Elderly patients (aged ≥65 years) who underwent radical gastrectomy for gastric cancer from August 2014 to June 2019 were included. Malnutrition was diagnosed using the GLIM criteria. Skeletal muscle index (SMI), skeletal muscle density (SMD), subcutaneous fat area (SFA), and visceral fat area (VFA) were analyzed using abdominal computed tomography (CT) images. Handgrip strength and 6-m gait speed were measured. RESULTS: A total of 597 elderly patients were included in this study, in which 45.7% were at risk of malnutrition identified using Nutritional Risk Screening 2002 (NRS 2002), and 34.5% were diagnosed with malnutrition. Patients with malnutrition had lower SMI, SMD, SFA, VFA, lower handgrip strength and gait speed. Low handgrip strength and age ≥80 years were independent risk factors for postoperative complications, rather than GLIM-defined malnutrition. GLIM-defined malnutrition was independently associated with overall survival and disease-free survival after adjusting to the body composition and functional parameters in the multivariate analyses. CONCLUSIONS: GLIM-defined malnutrition was a better predictive factor than single parameters of body composition or physical function for survival in elderly gastric cancer patients. Handgrip strength can be used as a supportive measure to further improve the definition of malnutrition.

Value of muscle quality, strength and gait speed in supporting the predictive power of GLIM-defined malnutrition for postoperative outcomes in overweight patients with gastric cancer.

BACKGROUND: The present study aims to investigate the prognostic value of Global Leadership Initiative in Malnutrition (GLIM)-defined malnutrition in overweight patients who underwent gastrectomy for gastric cancer, and to explore whether the addition of muscle quality, strength and gait speed could improve the predictive power for postoperative outcomes. METHODS: Overweight patients (body mass index (BMI) ≥23 kg/m2) who underwent radical gastrectomy for gastric cancer were included in this study. Malnutrition was diagnosed using the two-step approach following the GLIM criteria. Skeletal muscle mass and quality was assessed using computed tomography (CT) determined skeletal muscle index (SMI) and skeletal muscle density (SMD), respectively. Hand-grip strength and 6-m gait speed were measured before surgery. RESULTS: A total of 587 overweight patients were included, in which 262 patients were identified as having obesity (BMI ≥25 kg/m2). The prevalence of malnutrition was 11.9% and 10.7% for overweight and obese patients, respectively. GLIM-defined malnutrition alone was not predictive for postoperative complications in overweight patients. The addition of low gait speed or muscle quality to GLIM-defined malnutrition led to a significant predictive value for postoperative complications. Low gait speed plus GLIM-defined malnutrition remained significant in the multivariate analysis. GLIM-defined malnutrition was predictive for overall survival (OS) and disease-free survival (DFS). Addition of low gait speed to GLIM-defined malnutrition increased the hazard ratio (HR) for the prediction of OS and DFS (univariate analysis: 2.880 vs. 2.238 for OS, 2.410 vs. 1.937 for DFS; multivariate analysis: 2.836 vs. 1.841 for OS, 2.433 vs. 1.634 for DFS). Addition of low hand-grip strength to GLIM-defined malnutrition led to a higher HR for the prediction of OS (2.144 vs. 1.841) in the multivariate analysis. CONCLUSION: Muscle quality, strength and gait speed added prognostic value to GLIM-defined malnutrition for the prediction of postoperative complications and/or survival in overweight patients who underwent radical gastrectomy for gastric cancer, especially gait speed, which could be incorporated into nutritional assessment protocols.

Measurement of muscle quantity/quality has additional predictive value for postoperative complications and long-term survival after gastrectomy for gastric cancer in patients with probable sarcopenia as defined by the new EWGSOP2 consensus: Analysis from a large-scale prospective study.

OBJECTIVES: We investigated whether measurement of muscle quantity/quality has additional predictive value for postoperative complications and long-term survival after gastrectomy for gastric cancer in patients with probable sarcopenia, as defined by the new European Working Group on Sarcopenia in Older People 2 consensus. METHODS: We conducted a prospective study of patients who underwent a radical gastrectomy for gastric cancer between August 2014 and June 2019. Muscle strength was measured using a handgrip dynamometer. Computed tomography images at the third lumbar vertebra level were used to assess muscle quantity and quality by the measuring cross-sectional muscle area and mean muscle attenuation, respectively. Probable sarcopenia was defined by low muscle strength. Sarcopenia was diagnosed by additional low muscle quantity or quality. Clinical outcomes were obtained by prospective data collection and follow up. RESULTS: Probable sarcopenia was identified in 419 patients, including 285 patients with sarcopenia. Patients with sarcopenia had a higher incidence of postoperative complications, higher costs, longer length of postoperative hospital stay, and worse overall survival (OS) and disease-free survival (DFS) compared with patients with low muscle strength only. The multivariate logistic analysis showed that sarcopenia and hypoproteinemia were independent risk factors for postoperative complications in patients with probable sarcopenia. Moreover, multivariate Cox analyses showed that sarcopenia remained an independent risk factor for OS and DFS in patients with probable sarcopenia. CONCLUSIONS: The measurement of muscle quantity/quality has additional predictive value for postoperative complications, OS, and DFS after gastrectomy for gastric cancer in patients with probable sarcopenia.

Impact of Body Composition and Physical Function on Quality of Life After Gastrectomy for Gastric Cancer.

PURPOSE: Patients with gastric cancer after gastrectomy often suffer from a decline in their quality of life (QoL), but the relationship between body composition (BC) and physical function on QoL has rarely been studied. This study aims to evaluate and determine the changes in QoL after gastrectomy and the impact of BC and physical function on QoL. METHODS: A total of 311 gastric cancer patients completed EORTC QLQ-C30 and EORTC QLQ-STO22 questionnaires before and 1, 3, 6 months post-surgery. Data including BC, handgrip strength (HGS) and 6-m gait speed (GS) were collected prospectively. Multiple linear regression analysis was used to determine the correlation between QoL and BC, HGS and GS. RESULTS: Patients had significantly worse scores after surgery on most function and symptom scales (p < 0.001), but most of these scales recovered within 6 months after surgery. A higher subcutaneous fat area (SFA)was associated with increased symptom scores 1 month after surgery. A higher GS is associated with a better global health status symptom. CONCLUSION: Patients suffer from a decline in their QoL after gastrectomy for gastric cancer. Intervention strategies aiming at reducing SFA and improving GS may improve the QoL in patients underwent gastrectomy for gastric cancer.

Influence of body composition, muscle strength, and physical performance on the postoperative complications and survival after radical gastrectomy for gastric cancer: A comprehensive analysis from a large-scale prospective study.

BACKGROUND: Few studies have comprehensively analyzed the correlations among body composition parameters, muscle strength, and physical performance, as well as the influence of these factors on the postoperative complications and survival after radical gastrectomy for gastric cancer. METHODS: A prospective study was conducted including patients who underwent radical gastrectomy for gastric cancer from August 2014 to June 2019. Skeletal muscle index (SMI), skeletal muscle density (SMD), visceral fat area (VFA), subcutaneous fat area (SFA) was obtained by measurement of preoperative computed tomography (CT) images. Grip strength and 6-m gait speed were measured to assess muscle strength and physical performance before surgery. RESULTS: There was a positive correlation between SMI and SMD, as well as between SFA and VFA. SMD negatively correlated with SFA and VFA. SMI had a positive correlation with VFA, but showed minimal correlation with SFA and visceral to subcutaneous fat ratio (VSR). Grip strength and gait speed were both positively correlated with SMI and SMD, but showed minimal correlation with SFA, VFA and VSR. SMI and grip strength independently predicted postoperative complications, rather than SMD or gait speed. Whereas SMD and gait speed had independent predictive value for overall survival (OS) and/or disease-free survival (DFS), rather than SMI or grip strength. VSR independently predicted postoperative complications, rather than VFA or SFA alone. Low SFA was an independent risk factor for OS and DFS. High VFA was associated with worse survival in overweight patients (body mass index, BMI ≥25), but was associated with better survival in non-overweight patients (BMI <25). High SFA did not significantly influence survival in overweight patients, but was associated with better survival in non-overweight patients. CONCLUSION: There is an extensive and complex correlation among body composition parameters, grip strength, and gait speed in patients with operable gastric cancer. A comprehensive analysis of these parameters has significant predictive value for postoperative complications and survival.

Value of Sarcopenia defined by the new EWGSOP2 consensus for the prediction of Postoperative Complications and Long-term Survival after Radical Gastrectomy for Gastric Cancer: A comparison with four common nutritional screening tools.

Background: Nutritional risk and sarcopenia are both associated with increased postoperative morbidity and mortality following elective surgery. This study aimed to investigate whether sarcopenia has additional predictive value for postoperative complications and long-term survival besides nutritional screening tools. Methods: Clinical data of patients underwent radical gastrectomy for gastric cancer was prospectively collected. Sarcopenia was diagnosed by grip strength plus muscle quanlity/quality based on preoperative abdominal CT scans. Nutritional screening was performed using 4 common nutritional screening tools, including Malnutrition Universal Screening Tool (MUST), Nutritional Risk Screening (NRS)-2002, Malnutrition Screening Tool (MST), and Short Nutritional Assessment Questionnaire (SNAQ). Results: A total of 880 patients were analyzed, in which 167 (18.98%) were diagnosed with sarcopenia. The incidence of nutritional risk identified by the 4 tools were 44.66% (MUST ≥1), 35.23% (NRS-2002 ≥3), 29.89% (MST ≥2), and 20.34% (SNAQ ≥2). Multivariate analyses showed that nutritional risk identified by the 4 nutritional screening tools were not independently associated with postoperative complications, overall survival (OS) or disease-free survival (DFS), except for NRS-2002 ≥3 as an independent risk factor of OS. Sarcopenia was always an independent risk factor for postoperative complications, OS, and DFS after adjusting for nutritional risk and the other covariates in the multivariate analyses. Conclusions: MUST, NRS-2002, MST, and SNAQ had low predictive power for postoperative complications and long-term survival in patients underwent radical gastrectomy for gastric cancer. Sarcopenia had additional predictive value for postoperative complications and long-term survival besides these nutritional screening tools and should be implemented in the preoperative assessments.

Nrf2 deficiency promotes the increasing trend of autophagy during aging in skeletal muscle: a potential mechanism for the development of sarcopenia.

This study aims to explore the impact of nuclear factor erythroid 2-related factor 2 (Nrf2) deficiency on skeletal muscle autophagy and the development of sarcopenia. LC3b, P62, Bnip3, Lamp-1, and AMPK protein levels were measured in muscle from young, middle-aged, old Nrf2-/- (knockout, KO) mice and age-matched wild-type (WT) C57/BL6 mice. Autophagy flux was measured in young WT, young KO, old WT, old KO mice, using colchicine as autophagy inhibitor. There was a trend of higher accumulation of LC3b-II, P62, Bnip3, Lamp-1 induced by colchicine in old WT mice compared with young WT mice. Colchicine induced a significantly higher accumulation of LC3b-II, P62, Bnip3, Lamp-1 in KO mice compared with WT mice, both in the young and old groups. AMPK and reactive oxygen species (ROS) were unregulated following Nrf2 KO and increasing age, which was consistent with the increasing trend of autophagy flux following Nrf2 KO and increasing age. Nrf2 KO and increasing age caused decreased cross-sectional area of extensor digitorum longus and soleus muscles. We concluded that Nrf2 deficiency and increasing age may activate AMPK and ROS signals to cause excessive autophagy activation in skeletal muscle, which can be a potential mechanism for the development of sarcopenia.

Impact of sarcopenia on clinical outcomes after radical gastrectomy for patients without nutritional risk.

OBJECTIVE: The aim of this study was to investigate the prevalence of sarcopenia in patients without nutritional risk and the association between sarcopenia and postoperative outcomes after radical gastrectomy in these patients. METHOD: We conducted a study of non-nutritional risk patients with gastric cancer who underwent gastrectomy from August 2014 to December 2017 in two centers. Nutritional Risk Screening 2002 (NRS 2002) was used to evaluate the nutritional risk. Patients who with NRS 2002 score <3 were classified as having no nutritional risk and were included in the study. Demographic and perioperative data were gathered. Sarcopenia was diagnosed based on the European Working Group on Sarcopenia in Older People criteria. Univariate and multivariate analysis were performed to determine the association between preoperative risk factors and postoperative complications. RESULTS: In all, 545 patients were included, in which the prevalence of sarcopenia and postoperative complications was 7.3% and 21.1%, respectively. Sarcopenia was significantly associated with higher age, lower body mass index, lower handgrip strength, lower usual walking speed, longer postoperative hospital length of stay, and higher costs. Multivariate analysis of prognostic factors revealed that sarcopenia was an independent predictor (odds ratio, 2.330; 95% confidence interval, 1.132-4.796; P = 0.022] for postoperative complications. Male sex, diabetes, and preoperative anemia also were risk factors for postoperative complications. CONCLUSION: Sarcopenia was a significant independent risk factor for postoperative complications after gastrectomy in patients without nutritional risk. Preoperative assessment and management of sarcopenia should be helpful for improving clinical outcomes for patients without nutritional risk.

Nrf2 deficiency exacerbates frailty and sarcopenia by impairing skeletal muscle mitochondrial biogenesis and dynamics in an age-dependent manner.

AIM: Mitochondrial dysfunction during aging is a key factor that contributes to sarcopenia. Nuclear factor erythroid 2-related factor 2 (Nrf2) has been increasingly recognized to regulate mitochondrial function. The present study aimed to investigate the role of Nrf2 in the development of frailty and sarcopenia during aging, and to demonstrate whether Nrf2 contributes to the maintenance of muscle mass and function by regulation of mitochondrial biogenesis and dynamics during the aging process. METHODS: Young (5-6 months), middle-aged (11-13 months), old (20-24 months) Nrf2-/- (knockout, KO) mice and age-matched wild-type (WT) C57/BL6 mice were used in this study. Physical function of the mice in the 6 groups was assessed by grip strength test, four paw inverted hanging test, rotarod analysis, open field analysis, and treadmill endurance test. Muscle mass was measured by cross-sectional area (CSA) of tibialis anterior muscles and gastrocnemius muscle weight. The frailty status of the 25 old WT mice and 23 old KO mice were assessed based on the mouse frailty phenotype assessment. Expression levels of genes involved in mitochondrial biogenesis (nuclear respiratory factor 1 (Nrf1), peroxisome proliferative activated receptor, gamma, coactivator 1 alpha (PGC-1α), mitochondrial transcription factor A (TFAM)) and mitochondrial dynamics (optic atrophy protein 1 (Opa1), mitofusin 1 (Mfn1), mitofusin 2 (Mfn2), and dynamin-related protein 1 (Drp1)) were measured in the skeletal muscle. SDH staining was performed and mitochondrial DNA (mtDNA) copy number was measured. Transmission electron microscopy was used to measure the mitochondria number and morphology. RESULTS: Physical function and muscle mass decreased during aging. The mRNA expression levels of Nrf2 decreased with increasing frailty phenotype scores in the old WT mice. There were minimal differences in the physical function and muscle mass between the WT and KO mice in the young groups, whereas Nrf2 deficiency caused a declined physical function and muscle mass in the middle-aged and old mice, and exacerbated frailty in the old mice. The decreases of the physical function and muscle mass were accompanied by the reduced expression levels of genes involved in mitochondrial biogenesis and dynamics, as well as a reduction of mitochondrial number, mitochondrial content, mtDNA copy number, and an impaired mitochondria morphology in the skeletal muscle. CONCLUSION: Nrf2 deficiency exacerbated frailty and sarcopenia during aging, at least partially by impairing skeletal muscle mitochondrial biogenesis and dynamics in an age-dependent manner.

Comparison of three common nutritional screening tools with the new European Society for Clinical Nutrition and Metabolism (ESPEN) criteria for malnutrition among patients with geriatric gastrointestinal cancer: a prospective study in China.

OBJECTIVE: The aim of this study was to evaluate and compare three common nutritional screening tools with the new European Society for Clinical Nutrition and Metabolism (ESPEN) diagnostic criteria for malnutrition among elderly patients with gastrointestinal cancer. RESEARCH METHODSANDPROCEDURES: Nutritional screening tools, including the Nutritional Risk Screening 2002 (NRS 2002), the Malnutrition Universal Screening Tool (MUST) and the Short Form of Mini Nutritional Assessment (MNA-SF), were applied to 255 patients with gastrointestinal cancer. We compared the diagnostic values of these tools for malnutrition, using the new ESPEN diagnostic criteria for malnutrition as the 'gold standards'. RESULTS: According to the new ESPEN diagnostic criteria for malnutrition, 20% of the patients were diagnosed as malnourished. With the use of NRS 2002, 52.2% of the patients were found to be at high risk of malnutrition; with the use of MUST, 37.6% of the patients were found to be at moderate/high risk of malnutrition; and according to MNA-SF, 47.8% of the patients were found to be at nutritional risk. MUST was best correlated with the ESPEN diagnostic criteria (К=0.530, p<0.001) compared with NRS 2002 (К=0.312, p<0.001) and MNA-SF (К=0.380, p<0.001). The receiver operating characteristic curve of MUST had the highest area under the curve (AUC) compared with NRS 2002 and MNA-SF. CONCLUSIONS: Among the tools, MUST was found to perform the best in identifyingmalnourished elderly patients with gastrointestinal cancer distinguished by the new ESPEN diagnostic criteria for malnutrition. Nevertheless, further studies are needed to verify our findings. TRIAL REGISTRATION NUMBER: ChiCTR-RRC-16009831; Pre-results.