Thiyl Radical Trapped by Cobalt Catalysis: An Approach to Markovnikov Thiol-Ene Reaction.

In the presence of a thiyl radical species, the catalytic Markovnikov thiol-ene reaction is challenging because it prefers to proceed via a radical pathway, thereby leading to anti-Markovnikov selectivity. In this work, a rare example of thiyl radical engaged in Markovnikov thiol-ene reaction enabled by cobalt catalysis is reported. This protocol features the avoidance of unique oxidants, exclusive regioselectivity, and broad substrate scope. Scalable synthesis and late-stage modification of complex molecules demonstrate the practicability of the protocol.

Association between C-reactive protein-albumin-lymphocyte (CALLY) index and overall survival in patients with colorectal cancer: From the investigation on nutrition status and clinical outcome of common cancers study.

Background: Colorectal cancer (CRC) is among the most common malignant cancers worldwide, and its development is influenced by inflammation, nutrition, and the immune status. Therefore, we combined C-reactive protein (CRP), albumin, and lymphocyte, which could reflect above status, to be the CRP-albumin-lymphocyte (CALLY) index, and evaluated its association with overall survival (OS) in patients with CRC. Methods: The clinicopathological and laboratory characteristics of 1260 patients with CRC were collected from the Investigation on Nutrition Status and Clinical Outcome of Common Cancers (INSCOC) study. Cox regression analysis was performed to assess the association between the CALLY index and OS. A nomogram including sex, age, the CALLY index and TNM stage was constructed. The Concordance Index (C-index) was utilized to evaluate the prognostic value of the CALLY index and classical CRC prognostic factors, such as modified Glasgow prognostic score (mGPS), neutrocyte to lymphocyte ratio (NLR), systemic immune inflammation index (SII), and platelet to lymphocyte ratio (PLR), as well as to assess the prognostic value of the nomogram and TNM stage. Results: Multivariate Cox regression analyses demonstrated that the CALLY index was independently associated with OS in patients with CRC [Hazard ratio (HR) = 0.91, 95% confidence interval (CI) = 0.87-0.95, P<0.001]. The CALLY index showed the highest prognostic value (C-index = 0.666, 95% CI = 0.638-0.694, P<0.001), followed by mGPS, NLR, SII, and PLR. The nomogram demonstrated higher prognostic value (C-index = 0.784, 95% CI = 0.762-0.807, P<0.001) than the TNM stage. Conclusion: The CALLY index was independently associated with OS in patients with CRC and showed higher prognostic value than classical CRC prognostic factors. The nomogram could provide more accurate prognostic prediction than TNM stage.

AIWW: a new nutrition-screening tool for the oncologic population.

Malnutrition is a common comorbidity among patients with cancer. However, no nutrition-screening tool has been recognized in this population. A quick and easy screening tool for nutrition with high sensitivity and easy-to-use is needed. Based on the previous 25 nutrition-screening tools, the Delphi method was made by the members of the Chinese Society of Nutritional Oncology to choose the most useful item from each category. According to these results, we built a nutrition-screening tool named age, intake, weight, and walking (AIWW). Malnutrition was defined based on the scored patient-generated subjective global assessment (PG-SGA). Concurrent validity was evaluated using the Kendall tau coefficient and kappa consistency between the malnutrition risks of AIWW, nutritional risk screening 2002 (NRS-2002), and malnutrition screening tool (MST). Clinical benefit was calculated by the decision curve analysis (DCA), integrated discrimination improvement (IDI), and continuous net reclassification improvement (cNRI). A total of 11,360 patients (male, n=6,024 (53.0%) were included in the final study cohort, and 6,363 patients had malnutrition based on PG-SGA. Based on AIWW, NRS-2002, and MST, 7,545, 3,469, and 1,840 patients were at risk of malnutrition, respectively. The sensitivities of AIWW, NRS-2002, and MST risks were 0.910, 0.531, and 0.285, and the specificities were 0.768, 0.946, and 0.975. The Kendall tau coefficients of AIWW, NRS-2002, and MST risks were 0.588, 0.501, and 0.326, respectively. The area under the curve of AIWW, NRS-2002, and MST risks were 0.785, 0.739, and 0.630, respectively. The IDI, cNRI, and DCA showed that AIWW is non-inferior to NRS-2002 (IDI: 0.002 (-0.009, 0.013), cNRI: -0.015 (-0.049, 0.020)). AIWW scores can also predict the survival of patients with cancer. The missed diagnosis rates of AIWW, NRS-2002, and MST were 0.09%, 49.0%, and 73.2%, respectively. AIWW showed a better nutrition-screening effect than NRS-2002 and MST for patients with cancer and could be recommended as an alternative nutrition-screening tool for this population.

The prognostic value of the combination of body composition and systemic inflammation in patients with cancer cachexia.

BACKGROUND: Changes in body composition and systemic inflammation are important characteristics of cancer cachexia. This multi-centre retrospective study aimed to explore the prognostic value of the combination of body composition and systemic inflammation in patients with cancer cachexia. METHODS: The modified advanced lung cancer inflammation index (mALI), which combines body composition and systemic inflammation, was defined as appendicular skeletal muscle index (ASMI) × serum albumin/neutrophil-lymphocyte ratio. The ASMI was estimated according to a previously validated anthropometric equation. Restricted cubic splines were used to evaluate the relationship between mALI and all-cause mortality in patients with cancer cachexia. Kaplan-Meier analysis and Cox proportional hazard regression analysis were used to evaluate the prognostic value of mALI in cancer cachexia. A receiver operator characteristic curve was used to compare the effectiveness of mALI and nutritional inflammatory indicators in predicting all-cause mortality in patients with cancer cachexia. RESULTS: A total of 2438 patients with cancer cachexia were enrolled, including 1431 males and 1007 females. The sex-specific optimal cut-off values of mALI for males and females were 7.12 and 6.52, respectively. There was a non-linear relationship between mALI and all-cause mortality in patients with cancer cachexia. Low mALI was significantly associated with poor nutritional status, high tumour burden, and high inflammation. Patients with low mALI had significantly lower overall survival (OS) than those with high mALI (39.5% vs. 65.5%, P < 0.001). In the male population, OS was significantly lower in the low mALI group than in the high group (34.3% vs. 59.2%, P < 0.001). Similar results were also observed in the female population (46.3% vs. 75.0%, P < 0.001). mALI was an independent prognostic factor for patients with cancer cachexia (hazard ratio [HR] = 0.974, 95% confidence interval [CI] = 0.959-0.990, P = 0.001). For every standard deviation [SD] increase in mALI, the risk of poor prognosis for patients with cancer cachexia was reduced by 2.9% (HR = 0.971, 95%CI = 0.943-0.964, P < 0.001) in males and 8.9% (HR = 0.911, 95%CI = 0.893-0.930, P < 0.001) in females. mALI is an effective complement to the traditional Tumour, Lymph Nodes, Metastasis (TNM) staging system for prognosis evaluation and a promising nutritional inflammatory indicator with a better prognostic effect than the most commonly used clinical nutritional inflammatory indicators. CONCLUSIONS: Low mALI is associated with poor survival in both male and female patients with cancer cachexia and is a practical and valuable prognostic assessment tool.

Systemic inflammation with sarcopenia predicts survival in patients with gastric cancer.

OBJECTIVE: The levels of platelet-related inflammation indicators and sarcopenia have been reported to affect the survival of patients with cancer. To evaluate the prognostic influence of platelet count (PLT), platelet lymphocyte ratio (PLR), and systemic immune inflammation index (SII), and SII combined with sarcopenia on the survival of patients with gastric cancer (GC). METHODS: A total of 1133 patients with GC (812 male and 321 female, average age: 59.43 years) were evaluated. Receiver-operating characteristic curves were used to determine the best cutoff values of PLT, PLR, and SII, and univariate and multivariate Cox risk regression models were used to evaluate whether SII is an independent predictor of overall survival (OS). The prognostic SS (SII-sarcopenia) was established based on SII and sarcopenia. Finally, a comprehensive analysis of the prognostic SS was performed. RESULTS: SII had the strongest prognostic effect. The SII and OS of patients with GC were in an inverted U-shape (adjusted HR = 1.07; 95% CI 0.97-1.19; adjusted P = 0.179). In patients with SII > 1800, SII was negatively correlated with OS (adjusted HR = 0.57; 95% CI 0.29-1.12; adjusted P = 0.102), however, there is no statistical difference. Interestingly, a high SS was associated with a poorer prognosis. The higher the SS score was, the worse the OS (P < 0.001). CONCLUSION: SII is an independent prognostic indicator of GC, and high SII is related to poor prognosis. A higher SS score had worse survival. Thus, the prognostic SS is a reliable predictor of OS in patients with GC.

Association between systemic inflammation and water composition and survival in colorectal cancer.

Background: Systemic inflammation and water composition are important factors affecting cancer prognosis. This study aimed to explore the association between the neutrophil-to-lymphocyte ratio (NLR) and intracellular water/total body water (ICW/TBW) ratio and overall survival (OS) in colorectal cancer (CRC). Methods: This multicenter, prospective cohort included 628 patients with CRC between June 2012 and December 2019. The association between the covariates and OS was assessed using a Cox proportional hazards model and restricted cubic spline models. Concordance index (C-index), which integrated discriminant improvement (IDI) index and continuous net reclassification index, (cNRI) was used to compare the predictive ability of the markers. Results: The optimal cutoff values for the NLR and ICW/TBW ratio were 2.42 and 0.61, respectively. The NLR was negatively associated with OS, while the ICW/TBW ratio was positively correlated with OS. NLR ≥2.42 and ICW/TBW ratio <0.61 were both independent poor prognostic factors (hazard ratio [HR]: 2.04, 95% confidence interval [CI]: 1.44-2.88 and HR: 1.45, 95% CI: 1.04-2.02, respectively). Subsequently, we combined the two factors to construct an inflammation-water score (IWS). Patients with IWS (2, ≥1) had worse OS (HR: 2.86 and 95% CI: 1.77-4.63; HR: 1.74 and 95% CI 1.17-2.57, respectively) than those without one. Compared to its component factors, IWS score showed better predictive ability for C-index, IDI index, and cNRI. Conclusion: A high NLR and a low ICW/TBW ratio were independent risk factors for poor prognosis in patients with CRC. The combination of the two factors can provide a better prognostic prediction effect.

Association of systemic inflammation and low performance status with reduced survival outcome in older adults with cancer.

BACKGROUND: Inflammation is involved in the progression and prognosis of cancer because it can affect the physical status and prognosis of patients. Among numerous systemic inflammatory markers, the optimal prognostic indicator of older adults with cancer is still unclear. We aimed to identify an ideal inflammatory immune marker in older adults with cancer and assess the survival outcome combined with eastern cooperative oncology group performance status (ECOG PS). METHODS: We included 1767 older adults with cancer (66.2% males, 70.97 ± 5.49 years old) from a prospective cohort study. Fifteen systemic inflammatory biomarkers were compared to identify the optimal biomarker using prognostic area under the curve (AUC) and concordance index (C-index) analysis. The prognostic value of the clinical parameters was elucidated by performing uni- and multivariate analyses. RESULTS: The AUC, C-index, and the subgroup survival analysis of ECOG PS groups showed that the lymphocyte-C reactive protein ratio (LCR) and C-reactive protein/albumin ratio (CAR) were more accurate in reflecting patient prognosis than the other 13 inflammatory markers. Compared with patients in the high LCR group, those in the low LCR group had worse survival (hazard ratio (HR) 1.64, 95% confidence interval (95%CI) 1.42-1.91, p < 0.001). Compared with patients in the low CAR group, those in the high CAR group had worse survival (HR 1.65, 95% CI 1.43-1.91, p < 0.001). Older adults with cancer with an ECOG PS score of 2 or 3-4 and a high inflammation (low LCR, 13.3 months and 9.2 months, respectively; or high CAR, 9.6 months and 9.6 months, respectively) had shorter median survival time compared to those with an ECOG PS score of 0/1 and a low inflammation (high LCR, 77.4 months; or low CAR, 77.0 months). CONCLUSION: LCR and CAR might be the better predictive immune inflammatory factors for OS, which improved the survival prediction of different ECOG PS groups in older adults with cancer. High ECOG PS (≥2) and high inflammation increased the risk of death in older adults with cancer.

Association of serum total bilirubin with survival outcomes in patients with cancer cachexia: A prospective, multicenter cohort study.

OBJECTIVES: Cancer cachexia is a systemic paraneoplastic phenomenon involving multiple organs, including the liver. Total bilirubin (TBIL) is an easily obtained blood biomarker that reflects liver homeostasis. The aim of this study was to evaluate the prognostic value of serum TBIL in patients with cancer cachexia. METHODS: This study included 2282 patients from a multicenter research database who were diagnosed with cancer cachexia between June 2012 and December 2019. The hazard ratio (HR) for all-cause mortality was analyzed using Cox proportional hazards regression models. The association of serum TBIL with all-cause mortality was modeled with restricted cubic splines. The optimal cutoff value for TBIL was calculated with maximally selected rank statistics. RESULTS: Of the participants, there were 1327 (58.2%) men and 955 (41.8%) women. The mean patient age was 60.4 ± 1.5 y. The 12-mo all-cause mortality rate for patients with cancer cachexia was 29.5% (95% confidence interval [CI], 27.6%-31.3%), resulting in a rate of 209.58 events per 1000 patient-years. An inverted L-shaped association between TBIL and all-cause mortality was observed. The cutoff point for TBIL for the prediction of the time to mortality was <21.7 µmol/L. A high TBIL level but not the direct bilirubin or indirect bilirubin level was identified as an independent prognostic factor (HR, 1.60; 95% CI, 1.32-1.93). For patients with digestive system tumors, a high serum TBIL level (≥21.7 µmol/L) was significantly associated with mortality. CONCLUSION: High TBIL levels are associated with increased all-cause mortality in patients and might be a promising prognostic indicator in patients with cancer cachexia.

Prognostic Roles of Glucose to Lymphocyte Ratio and Modified Glasgow Prognosis Score in Patients With Non-small Cell Lung Cancer.

Background: Non-small cell lung cancer (NSCLC) is among the most prevalent malignancies worldwide. Previous studies have shown that the status of inflammation, nutrition and immune are closely related to overall survival (OS) of patients with NSCLC, but little is known about their interactive and combined roles. Hence, we chose glucose to lymphocyte ratio (GLR) and modified Glasgow Prognosis Score (mGPS) as prognostic factors and assessed the prognostic values of them for patients with NSCLC. Methods: Baseline clinicopathologic and laboratory characteristics of 862 patients with NSCLC were obtained from a multicenter prospective cohort. The Cox proportional hazard regression models were used to determine prognostic values of the clinical factors. A nomogram was also constructed integrating the clinical factors with clinical significance or independent prognostic values. Concordance index (C-index) was utilized to evaluate the prediction accuracy of the TNM stage and the nomogram. Results: Multivariate analyses demonstrated that GLR [Hazard ratio (HR) = 1.029, 95% confidence interval (CI) = 1.004-1.056, P = 0.023] and mGPS (score of 1: HR = 1.404, 95% CI = 1.143-1.726, P = 0.001; score of 2: HR = 1.515, 95% CI = 1.159-1.980, P = 0.002) were independent prognostic factors for patients with NSCLC. The C-indexes of the TNM stage and the nomogram were 0.642 (95% CI = 0.620-0.663) and 0.694 (95% CI = 0.671-0.717), respectively. Conclusion: GLR and mGPS were independent prognostic factors for patients with NSCLC. Moreover, our constructed nomogram might be superior in predicting prognosis of patients with NSCLC compared with the TNM stage.

Extracellular water to total body water ratio predicts survival in cancer patients with sarcopenia: a multi-center cohort study.

BACKGROUND: Body water measured by bioelectrical impedance analysis (BIA) predicts the outcomes of many diseases. This study aimed to evaluate the relationship between body water and the prognosis of cancer patients with sarcopenia. METHODS: This study employed 287 cancer patients with sarcopenia underwent BIA from a prospective multicenter study of patients with cancer in China from 2013 to 2020. The primary outcome of interest was all-cause mortality presented as the longest time to follow-up available. Eight indicators of body water [total body water, extracellular water, intracellular water, free fat mass, active cell mass, extracellular water/intracellular water, extracellular water/total body water (ECW/TBW), and intracellular water/total body water] were included in the research. Neutrophil-lymphocyte ratio (NLR) = neutrophil (× 109)/lymphocyte (× 109). The discriminatory ability and prediction accuracy of each factor were assessed using the C-index. The hazard ratios (HR) and 95% confidence intervals (CI) were calculated using the Cox proportional hazard model. RESULTS: The median age was 65 years old, and 138 (48%) patients were men. During a mean follow-up of 46 months, 140 deaths were recorded, resulting in a rate of 204.6 events per 1000 patient-years. ECW/TBW showed the best predictive accuracy (C-index = 0.619) compared to the other indicators [p = 0.004, adjusted HR (95% CI) 1.70 (1.18,2.44)]. In the middle tertile (0.385-0.405), ECW/TBW had a strong independent negative association with patient survival [adjusted HR (95% CI) 2.88 (1.39-5.97), p = 0.004]. Patients who had a high ECW/TBW (ECW/TBW ≥ 0.395) combined with a high NLR had 3.84-fold risk of mortality (p < 0.001, 95% CI 1.99,7.38). CONCLUSIONS: ECW/TBW was better than other indicators in predicting survival of cancer patients with sarcopenia. High ECW/TBW combined with high NLR would further increase the risk of mortality. TRIAL REGISTRATION: The Investigation on Nutrition Status and Clinical Outcome of Common Cancers (INSCOC) (Chinese Clinical Trial Registry: ChiCTR1800020329, URL of registration: http://www.chictr.org.cn/showprojen.aspx?proj=31813 ).

The prognostic effect of hemoglobin on patients with cancer cachexia: a multicenter retrospective cohort study.

OBJECTIVES: To clarify the influence of hemoglobin on cancer cachexia and to determine whether hemoglobin affects the prognosis or quality of life of patients with cancer cachexia and whether these effects are caused by an interaction between hemoglobin and other factors. MATERIAL AND METHODS: This study was a multicenter cohort of 2715 patients with cancer cachexia diagnosed from June 2012 to December 2019. The primary outcomes and measures were overall survival (OS) time and all-cause mortality. The association between hemoglobin and all-cause mortality was evaluated using hazard ratios (HRs) and the restricted cubic spline model with a two-sided p-value. Optimal stratification was used to determine the threshold value. We also evaluated the cross-classification of hemoglobin and each variable with survival. RESULTS: Among the 2715 participants diagnosed with cancer cachexia, 1592 (58.6%) were male, and the mean (SD) age was 58.8 (11.7) years. The optimal cutoff point for hemoglobin as a predictor of cancer cachexia mortality was 140 g/L for males and 101 g/L for females in our research. The decrease in hemoglobin was positively correlated with all-cause mortality. These associations were consistent across cancer subtypes. In the multivariable analysis, after adjusting for sex, age, TNM stage, tumor type, radiotherapy, chemotherapy, Karnofsky performance status score, and other factors, patients diagnosed with cancer cachexia who had low hemoglobin levels were more likely to have a worse prognosis (HR 2.40; 95% CI, 1.12-1.51). CONCLUSION: Our results suggested that the proposed hemoglobin cutoff point would be valuable for prognostic prediction in patients with cancer cachexia, especially for long-term prognosis.

PG-SGA SF in nutrition assessment and survival prediction for elderly patients with cancer.

BACKGROUND: This study was sought to report the prevalence of malnutrition in elderly patients with cancer. Validate the predictive value of the nutritional assessment tool (Patient-Generated Subjective Global Assessment Short Form, PG-SGA SF) for clinical outcomes and assist the therapeutic decision. METHODS: This is a secondary analysis of a multicentric, observational cohort study. Elderly patients with cancer older than 65 years were enrolled after the first admission. Nutritional status was identified using the PG-SGA SF. RESULTS: Of the 2724 elderly patients included in the analysis, 65.27% of patients were male (n = 1778); the mean age was 71.00 ± 5.36 years. 31.5% of patients were considered malnourished according to PG-SGA SF. In multivariate analysis, malnutrition(PG-SGA SF > 5) was significantly associated with worse OS (HR: 1.47,95%CI:1.29-1.68), affects the quality of life, and was related to more frequent nutrition impact symptoms. During a median follow-up of 4.5 years, 1176 death occurred. The mortality risk was 41.10% for malnutrition during the first 12 months and led to a rate of 323.98 events per-1000-patient-years. All nutritional assessment tools were correlated with each other (PG-SGA SF vs. PG-SGA: r = 0.98; PG-SGA SF vs. GLIM[Global Leadership Initiative on Malnutrition]: r = 0.48, all P < 0.05). PG-SGA SF and PG-SGA performed similarly to predict mortality but better than GLIM. PG-SGA SF improves the predictive ability of the TNM classification system for mortality in elderly patients with cancer, including distinguishing patients' prognoses and directing immunotherapy. CONCLUSIONS: The nutritional status as measured by PG-SGA SF which is a prognostic factor for OS in elderly cancer patients and could improve the prognostic model of TNM.

Association of Systemic Inflammation and Overall Survival in Elderly Patients with Cancer Cachexia - Results from a Multicenter Study.

BACKGROUND: Systemic inflammation and cachexia are associated with adverse clinical outcomes in elderly patients with cancer. The survival outcomes of elderly patients with cancer cachexia (EPCC) with high inflammation and a high risk of mortality are unknown. This study aimed to investigate the impact of high inflammation on the prognosis of EPCC patients with high mortality. PATIENTS AND METHODS: This multicenter cohort study included 746 EPCC (age >65 years) with a mean age of 72.00 ± 5.24 years, of whom 489 (65.5%) were male. The cut-off value for the inflammation index was obtained using the optimal survival curve. The different inflammatory indicators were assessed using the concordance index (C-index), decision curve analysis (DCA), and prognostic receiver operating characteristic (ROC). The high mortality risk group of EPCC was defined by the 2011 Fearon Cancer Diagnostic Consensus. EPCC were divided into the high-risk group, which satisfies three diagnostic criteria, and a low-risk group, which satisfies only one or two diagnostic criteria. RESULTS: The C-index, DCA, and prognostic ROC indicated the superiority of advanced lung cancer inflammation index (ALI) compared with other indicators, including neutrophil-lymphocyte ratio (NLR), prognostic nutritional index (PNI), systemic immune-inflammation index (SII), and platelet-lymphocyte ratio (PLR). Whether ALI was used as a continuous or a categorical variable, ALI had a better prognostic value in EPCC compared with other inflammatory indicators. In particular, patients with low ALI (<25.03) had a worse overall survival (OS) than patients with high ALI (≥25.03) (P < 0.001, HR [95% CI] = 2.092 [1.590-2.751]). The combination effect analysis showed that the risk of mortality of the patients in the low-ALI and high-risk groups was 3.095-fold higher than that of patients in the high-ALI and low-risk groups. CONCLUSION: The prognostic and discriminative value of the inflammatory indicator ALI was better than that of NLR, PNI, SII, and PLR in EPCC. The high-risk group of EPCC with a low ALI would increase the death risk of OS.

Prevalence and Prognostic Value of Malnutrition Among Elderly Cancer Patients Using Three Scoring Systems.

Background: Malnutrition is common in patients with cancer and is associated with adverse outcomes, but few data exist in elderly patients. The aim of this study was to report the prevalence of malnutrition using three different scoring systems and to examine the possible clinical relationship and prognostic consequence of malnutrition in elderly patients with cancer. Methods: Nutritional status was assessed by using controlling nutritional status (CONUT), the prognostic nutritional index (PNI), and the nutritional risk index (NRI). Quality-of-life (Qol) was assessed during admission by using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C-30. Performance status (PS) was assessed by using the Eastern Cooperative Oncology Group (ECOG) classification. The relationship between nutritional status and overall survival and Qol were examined. Results: Data were available for 1,494 elderly patients with cancer (63.65% male), the mean age was 70.76 years. According to the CONUT, NRI, and PNI, 55.02, 58.70, and 11.65% patients were diagnosed with malnutrition, respectively. Worse nutritional status was related to older, lower BMI, lower hand grip strength, and more advanced tumor stage. All malnutrition indexes were correlated with each other (CONUT vs. PNI, r = -0.657; CONUT vs. NRI scores, r = -0.672; PNI vs. NRI scores, r = 0.716, all P < 0.001). During a median follow-up of 43.1 months, 692 (46.32%) patients died. For patients malnourished, the incidence rate (events-per-1,000person-years) was as follows: CONUT (254.18), PNI (429.91), and NRI (261.87). Malnutrition was associated with increased risk for all-cause mortality (adjust HR [95%CI] for CONUT: 1.09 [1.05-1.13], P < 0.001; PNI: 0.98[0.97-0.99], P < 0.001; NRI: 0.98 [0.98-0.99], P < 0.001). All malnutrition indexes improved the predictive ability of the TNM classification system for all-cause mortality. Deterioration of nutritional status was associated with deterioration in Qol parameters and immunotherapeutic response (P < 0.001). Conclusions: Malnutrition was prevalent in elderly patients with cancer, regardless of the assessment tools used, and associated with lower Qol and the immunotherapy response.

Evaluation and Validation of the Prognostic Value of Serum Albumin to Globulin Ratio in Patients With Cancer Cachexia: Results From a Large Multicenter Collaboration.

BACKGROUND: Recently, albumin-globulin ratio (AGR), a serological indicator that reflects nutritional status and systemic inflammatory, has been reported to be associated with the prognosis of various cancers. However, there is currently no research report on its relationship with cancer cachexia. OBJECTIVES: This study aimed to explore the prognostic value of AGR in patients with cancer cachexia through a multicenter retrospective analysis. METHODS: We recruited 2,364 patients with cancer cachexia and randomly divided the patients into training and validation cohorts at a ratio of 7:3. The optimal stratification method was used to determine the optimal cutoff value of AGR. The survival curve was evaluated by the Kaplan-Meier method. Cox regression proportional-hazards model was used to determine independent prognostic factors in patients with cancer cachexia. The time-dependent receiver operating characteristic curve was used to compare the prognostic performance of different malnutrition evaluation tools. RESULTS: The optimal cutoff value of AGR is 1.24 in patients with cancer cachexia. Increasing AGR was associated with survival in a dose-response manner with a forward L-shape. Compared with the high AGR group, the low AGR group had a shorter overall survival; and there was consistency in training and validation cohorts. In the stratified analysis of TNM stage, AGR has good prognostic distinguishing ability for advanced patients. Multivariate survival analysis determined that low AGR was an independent risk factor affecting all-cause mortality in patients with cancer cachexia. In addition, compared with other malnutrition evaluation tools, AGR could effectively stratify the prognosis of patients with cancer cachexia. CONCLUSION: AGR was an independent prognostic factor affecting patients with cancer cachexia, especially in advanced patients. Compared with other malnutrition evaluation tools, AGR can effectively stratify the prognosis of patients with cancer cachexia.

Geriatric Nutrition Risk Index: Prognostic factor related to inflammation in elderly patients with cancer cachexia.

BACKGROUND: Systemic inflammation and cachexia are associated with adverse clinical outcomes in elderly patients with cancer. The Geriatric Nutritional Risk Index (GNRI) is a simple and useful tool to assess these conditions, but its predictive ability for elderly patients with cancer cachexia (EPCC) is unknown. METHODS: This multicentre cohort study included 746 EPCC with an average age of 72.00 ± 5.24 years, of whom 489 (65.5%) were male. The patients were divided into two groups (high GNRI group ≥91.959 vs. low GNRI group <91.959) according to the optimal cut-off value of the ROC curve. The calibration curves were performed to analyse the prognostic, predictive ability of GNRI. Comprehensive survival analyses were utilized to explore the relationship between GNRI and the overall survival (OS) of EPCC. Interaction analysis was used to investigate the comprehensive effects of low GNRI and subgroup parameters on the OS of EPCC. RESULTS: In this study, a total of 2560 patients were diagnosed with cancer cachexia, including 746 cases of EPCC. During the 3.6 year median follow-up, we observed 403 deaths. The overall mortality rate for EPCC at 12 months was 34.3% (95% CI: 62.3% to 69.2%), and resulting in rate of 278 events per 1000 patient-years. The GNRI score of EPCC was significantly lower than those of young patients with cancer cachexia (P < 0.001). The 1, 3, and 5 year calibration curves showed that the GNRI score had good survival prediction in the OS of EPCC. The GNRI could predict the OS of EPCC, whether as a continuous variable or a categorical variable. Particularly, we also found that low GNRI score (<91.959) of EPCC had a worse prognosis than those with a high GNRI score (≥91.959, P = 0.001, HR = 1.728, 95% CI: 1.244-2.401). Consistent results were observed in the tumour subgroups of gastric cancer and colorectal cancer. Notably, similar results were observed in the sensitivity analysis. In the subgroup analysis, the low GNRI has a combined effect with age (<70 years) on poor OS of EPCC. The results of the prognostic risk model found that the lower the GNRI score, the greater the prognostic risk score, and the greater the risk of death in EPCC. CONCLUSIONS: For the first time, this study found that the GNRI score can serve as an independent prognostic factor for the OS of EPCC.

Association of systemic inflammation with survival in patients with cancer cachexia: results from a multicentre cohort study.

BACKGROUND: Although systemic inflammation is an important feature of the cancer cachexia, studies on the association between systemic inflammation and prognostic of cancer cachexia are limited. The objective of this study is to evaluate whether the neutrophil-to-lymphocyte ratio (NLR) is associated with outcome and quality of life for patients with cancer cachexia and investigated any interaction between NLR and the clinical parameters. METHODS: This is a multicentre cohort study of 2612 cancer patients suffering from cachexia diagnosed between June 2012 and December 2019. The main parameters measured were overall survival (OS) time and all-cause mortality. The association between NLR and all-cause mortality was evaluated using hazard ratios (HRs) and the restricted cubic spline model with a two-sided P-value. Optimal stratification was used to solve threshold points. We also evaluated the cross-classification of NLR for each variable of survival. RESULTS: Of the 2612 participants diagnosed with cancer cachexia, 1533 (58.7%) were male, and the mean (SD) age was 58.7 (11.7) years. Over a median follow-up of 4.5 years, we observed 1189 deaths. The overall mortality rate for patients with cancer cachexia during the first 12 months was 30.2% (95%CI: 28.4%-32.0%), resulting in a rate of 226.07 events per 1000 patient-years. An increase in NLR had an inverted L-shaped dose-response association with all-cause mortality. The optimal cut-off point for NLR as a predictor of mortality in cancer patients with cachexia was 3.5. An NLR of 3.5 or greater could independently predict OS (HR, 1.51, 95%CI: 1.33-1.71). These associations were consistent across subtypes of cancer. Several potential effect modifiers were identified including gender, BMI, tumour type, KPS score and albumin in content. Increasing NLRs were independently associated with a worsening in the majority of EORTC QLQ-C30 domains. Elevated baseline NLR was associated with low response and poor survival in patients treated with immunotherapy. CONCLUSIONS: The baseline NLR status was found to be a significant negative prognostic biomarker for patients with cachexia; this effect was independent of other known prognostic factors.

Sex Disparity in Bilateral Asymmetry of Impact Forces during Height-Adjusted Drop Jumps.

Side-to-side asymmetry of lower extremities may influence the risk of injury associated with drop jump. Moreover, drop heights using relative height across individuals based on respective jumping abilities could better explain lower-extremity loading impact for different genders. The purpose of the current study was to evaluate the sex differences of impact forces and asymmetry during the landing phase of drop-jump tasks using drop heights, set according to participants' maximum jumping height. Ten male and ten female athletes performed drop-jump tasks on two force plates, and ground reaction force data were collected. Both feet needed to land entirely on the dedicated force plates as simultaneously as possible. Ground reaction forces and asymmetry between legs were calculated for jumps from 100%, 130%, and 160% of each participant's maximum jumping height. Females landed with greater asymmetry at time of contact initiation and time of peak impact force and had more asymmetrical peak impact force than males. Greater values and shorter time after ground contact of peak impact force were found when the drop height increased to 160% of maximum jumping ability as compared to 100% and 130%. Females exhibited greater asymmetry than males during drop jumps from relative heights, which may relate to the higher risk of anterior cruciate ligament injury among females. Greater sex disparity was evident in impact force asymmetry than in the magnitude of peak impact force; therefore, it may be a more appropriate field-screening test for risk of anterior cruciate ligament injury.

Association Between Systemic Inflammation and Malnutrition With Survival in Patients With Cancer Sarcopenia-A Prospective Multicenter Study.

OBJECTIVE: Systemic inflammation and malnutrition are correlated with cancer sarcopenia and have deleterious effects on oncological outcomes. However, the combined effect of inflammation and malnutrition in patients with cancer sarcopenia remains unclear. METHODS: We prospectively collected information on 1,204 patients diagnosed with cancer sarcopenia. the mean (SD) age was 64.5 (11.4%) years, and 705 (58.60%) of the patients were male. The patients were categorized into the high advanced lung cancer inflammation index (ALI) group (≥18.39) and the low ALI group (<18.39) according to the optimal survival cut-off curve. We selected the optimal inflammation marker using the C-index, decision curve analysis (DCA), and a prognostic receiver operating characteristic curve. Univariate and multivariate survival analyses were performed to determine the prognostic value of the optimal inflammation indicator. We also analyzed the association between inflammation and malnutrition in patients with cancer. RESULTS: The C-index, DCA, and prognostic area under the curve of ALI in patients with cancer sarcopenia were higher or better than those of neutrophil-lymphocyte ratio (NLR), prognostic nutritional index (PNI), systemic immune-inflammation index (SII), and platelet-lymphocyte ratio (PLR). The prognosis for patients in the low ALI group was worse than that of patients in the high ALI group [HR (95%CI) = 1.584 (1.280-1.959), P < 0.001]. When the ALI was divided into quartiles, we observed that decreased ALI scores strongly correlated with decreased overall survival (OS). Patients with both a low ALI and severe malnutrition (vs. patients with high ALI and well-nourished) had a 2.262-fold death risk (P < 0.001). Subgroup analysis showed a significant interactive association between the ALI and death risk in terms of TNM stage (P for interaction = 0.030). CONCLUSIONS: The inflammation indicator of the ALI was better than those of the NLR, PNI, SII, and PLR in patients with cancer sarcopenia. Inflammation combined with severe malnutrition has a nearly 3-fold death risk in patients with cancer sarcopenia, suggesting that reducing systemic inflammation, strengthening nutritional intervention, and improving skeletal muscle mass are necessary.

Synthesis of di(hetero)aryl sulfides by defluorinative sulfenylation of polyfluoroalkyl ketones with sodium sulfinates or arylsulfonyl chlorides.

A facile incorporation of a privileged sulfide, a naphthofuran framework, and a perfluoroalkyl moiety in one molecule was successfully accomplished through tandem defluorinative sulfenylation of α-perfluoroalkyl ketones with a sulfur source. The reaction presumably proceeds via a sequence involving defluorination, reductive sulfenylation, autoaromatization, and annulation, accompanied by the simultaneous cleavage of four C(sp3)-F bonds and the formation of new C-S and C-O bonds.