Rare Driver Mutations in Advanced, Oncogene-Addicted Non-Small Cell Lung Cancer: A North Italian, Real-World, Registry Experience.

The real-world, retrospective, NEROnE registry investigated the impact of next-generation sequencing (NGS) in advanced non-small-cell lung cancer (NSCLC) patients (pts) at three oncology units in the north of Italy between January 2020 and December 2022. We focused on the clinical characterization and outcomes of NSCLC with rare molecular alterations: EGFR exon 20 insertion, non-activating EGFR mutations, BRAF V600E and non-V600, ROS1 and RET rearrangements, MET, ErbB2, and FGFR mutations. Overall, these represented 6.4% (62/970) of the pts analysed with NGS in the daily practice. The most heavily represented rare alterations were ROS1 rearrangement (15 pts-24%) and MET exon 14 skipping mutation (11 pts-18%). No associations were found with the demographic and clinical features. Forty-nine pts received targeted therapies, of which 38.8% were first- and 9.8% were second-line. The remaining pts received chemotherapy and/or immunotherapy. In terms of the clinical outcomes, although not statistically significant, a tendency toward shorter OS was seen when therapies other than specific targeted therapies were used (HR: 1.84, 95% CI: 0.79-4.33, p = 0.158). The pts with co-mutations (19.4%) seemed to receive an advantage from the front-line chemotherapy-based regimen. Finally, an NLR score (a well-known inflammatory index) ≥ 4 seemed to be related to shorter OS among the pts treated with immunotherapy alone or in combination with chemotherapy (HR: 2.83, 95% CI: 1.08-7.40, p = 0.033). Prospective evaluations need to be performed to clarify whether these indexes may help to identify patients with oncogene-addicted NSCLC who could benefit from immunotherapy.

Prognostic role of circulating cytokines and inflammation indexes for avelumab maintenance in metastatic urothelial carcinoma.

Background: Avelumab maintenance after first-line platinum-based chemotherapy represents a cornerstone for the treatment of metastatic urothelial carcinoma (mUC). However, identifying prognostic biomarkers is paramount for optimizing patients' benefits while minimizing toxicity. Cytokines represent circulating mediators of the complex interaction between cancer, the immune system, and inflammation. Inflammation, a hallmark of cancer, can be expressed by circulating factors. In different tumor subtypes, peripheral blood biomarkers, such as circulating cytokines, and systemic inflammatory indexes, have been addressed as potential prognostic factors for immune checkpoint inhibitors. However, their role in mUC still needs to be determined. Methods: Between February 2021 and April 2023, we prospectively collected plasma cytokines and inflammation indexes in 28 patients with mUC before starting avelumab as first-line maintenance. The primary endpoint was the relationship between baseline cytokines and inflammatory indexes with the clinical benefit (CB), defined as the number of Responders. Secondary endpoints included the correlation of baseline cytokines and inflammatory indexes with progression-free survival (PFS), overall survival (OS), and the number and grade of immune-related adverse events. Results: High pre-treatment levels of interferon (IFN)-γ and interleukin (IL)-2, and low levels of IL-6, IL-8, neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), and systemic-inflammation index (SII) were associated with clinical benefit and longer survival. In the multivariate analysis, low IL-8, NLR, and SII levels maintained a positive prognostic value for OS. Conclusion: Our data suggest that, in mUC patients receiving avelumab, pre-treatment levels of plasma cytokines and inflammatory indexes may serve as potential prognostic biomarkers for response and efficacy. In particular, patients with signs of pre-therapeutic inflammation showed a significantly lower response and survival to avelumab. On the contrary, low systemic inflammation and high levels of cytokines characterized responders and longer survivors.

Comprehensive analysis of the association between inflammation indexes and complications in patients undergoing pancreaticoduodenectomy.

Background: During clinical practice, routine blood tests are commonly performed following pancreaticoduodenectomy (PD). However, the relationship between blood cell counts, inflammation-related indices, and postoperative complications remains unclear. Method: We conducted a retrospective study, including patients who underwent PD from October 2018 to July 2023 at the First Hospital of Chongqing Medical University, and compared baseline characteristics and clinical outcomes among different groups. Neutrophil count (NC), platelet count (PLT), lymphocyte count (LC), systemic immune-inflammation index (SII), platelet-to-lymphocyte ratio (PLR), neutrophil-to-lymphocyte ratio (NLR), and the product of platelet count and neutrophil count (PPN) were derived from postoperative blood test results. We investigated the association between these indicators and outcomes using multivariable logistic regression and restricted cubic spline analysis. The predictive performance of these indicators was assessed by the area under the curve (AUC) of the receiver operating characteristic (ROC) curve and decision curve analysis (DCA). Result: A total of 232 patients were included in this study. Multivariate logistic regression and restricted cubic spline analysis showed that all indicators, except for PLT, were associated with clinical postoperative pancreatic fistula (POPF). SII, NLR, and NC were linked to surgical site infection (SSI), while SII, NLR, and PLR were correlated with CD3 complication. PLT levels were related to postoperative hemorrhage. SII (AUC: 0.729), NLR (AUC: 0.713), and NC (AUC: 0.706) effectively predicted clinical POPF. Conclusion: In patients undergoing PD, postoperative inflammation-related indices and blood cell counts are associated with various complications. NLR and PLT can serve as primary indicators post-surgery for monitoring complications.

Inflammatory indices as prognostic markers in metastatic colorectal cancer patients treated with chemotherapy plus Bevacizumab.

Background: Validated predictors of sensitivity or resistance to Bevacizumab (Bev) are not available, and Inflammatory Indexes (IIs) has been reported to be useful prognostic factors in various malignant solid tumours, including metastatic colorectal cancer (mCRC). Objectives: To explore the prognostic value of IIs in mCRC patients treated with first-line chemotherapy plus Bev. Design: One hundred and eighty-two patients diagnosed with mCRC and treated with first line chemotherapy plus Bev were considered for this prospective non-pharmacological study. Neutrophil, lymphocyte, platelet, aspartate transaminase (AST) and lactate dehydrogenase (LDH) tests were carried out at baseline and before each treatment cycle, according to clinical practice. Methods: Pre-treatment Systemic Immune-inflammation Index (SII), Colon Inflammatory Index (CII) and Aspartate aminotransferase-Lymphocyte Ratio Index (ALRI) were evaluated to assess a correlation with progression-free survival (PFS) and overall survival (OS). Results: In the overall population, PFS and OS were lower in patients with high SII (HR 1.64, p = 0.006 and HR 1.75, p = 0.004, respectively) and high ALRI (HR 2.13, p = 0.001 and HR 1.76, p = 0.02, respectively), but no difference was detected according to CII value. The multivariate analysis confirmed both SII and ALRI as independent prognostic factors for PFS (HR 1.64 and 2.82, respectively) and OS (HR 1.65 and 2.12, respectively). Conclusion: Our results demonstrate and confirm that IIs, and in particular SII and ALRI, are easy to measure prognostic markers for patient candidates to first line chemotherapy plus Bev for mCRC.

Inflammatory Indexes can predict the efficacy of bevacizumab in metastatic colorectal cancer Bevacizumab (Bev) is a humanized monoclonal antibody with antiangiogenic activity, used in combination with chemotherapy as a standard first line treatment for many metastatic colorectal cancer patients. Validated predictors of sensitivity or resistance to Bevacizumab are not available, although several studies have investigated this issue in recent years. In this study, we investigated whether some selected baseline inflammatory indexes levels, namely Systemic Immune-inflammation Index (SII) and Aspartate aminotransferase-Lymphocyte Ratio Index (ALRI) could predict the survival in patients with metastatic colorectal cancer treated with Bevacizumab plus chemotherapy. We enrolled 182 patients diagnosed with mCRC and treated with first line chemotherapy plus Bev. For each patient we tested blood neutrophils, lymphocytes, platelets, aspartate transaminase (AST) and lactate dehydrogenase (LDH) before each treatment cycle, according to clinical practice. We calculated the SII value as platelet count × neutrophil count/lymphocyte count, and ALRI as AST/lymphocyte count. We found that patients with high SII and high ALRI values had lower survival as compared to those with low values. These parameters represent reproducible, inexpensive and easy to measure biomarkers to be used in both clinical practice and clinical trials, for patient selection.

Can gallbladder wall thickness and systemic inflammatory index values predict the possibility of conversion from laparoscopy to open surgery?

Background/Objective: This study aims to develop an objective marker that predicts the risk of conversion from laparoscopy to open surgery using gallbladder wall thickness and inflammatory index values. Materials and Methods: A total of 2,920 cholecystectomy patients were screened, including those whose operations were converted to open and those who underwent laparoscopy. A total of 700 cholecystectomy patients who met the study criteria were included in the study. The same team of surgeons performed all operations. The conversion probability from laparoscopic to open cholecystectomy was calculated using the ratio obtained by evaluating inflammatory markers and gallbladder wall thickness (K). The preoperative complete blood count and abdominal ultrasound data of the patients were obtained from our university patient registry system. Results: Age, neutrophil count, gallbladder wall thickness, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), KxNLR, and KxPLR values were all significantly higher in the conversion from laparoscopy to open surgery group compared with the laparoscopic cholecystectomy group. According to the ROC analysis performed on the gallbladder wall thickness values according to the probability of conversion to open surgery, the cutoff value was determined as >3 mm. Gallbladder wall thickness >KxPLR >KxNLR was defined as the diagnostic value order according to the area under the curve. Conclusions: The results of this study showed that gallbladder wall thickness effectively determines the probability of conversion from laparoscopy to open cholecystectomy and multiplying the gallbladder wall thickness (mm) by NLR increased the sensitivity.

Stratification of Amniotic Fluid Cells and Amniotic Fluid by Sex Opens Up New Perspectives on Fetal Health.

Amniotic fluid is essential for fetus wellbeing and is used to monitor pregnancy and predict fetal outcomes. Sex affects health and medicine from the beginning of life, but knowledge of its influence on cell-depleted amniotic fluid (AF) and amniotic fluid cells (AFCs) is still neglected. We evaluated sex-related differences in AF and in AFCs to extend personalized medicine to prenatal life. AFCs and AF were obtained from healthy Caucasian pregnant women who underwent amniocentesis at the 16th-18th week of gestation for advanced maternal age. In the AF, inflammation biomarkers (TNFα, IL6, IL8, and IL4), malondialdehyde, nitrites, amino acids, and acylcarnitines were measured. Estrogen receptors and cell fate (autophagy, apoptosis, senescence) were measured in AFCs. TNFα, IL8, and IL4 were higher in female AF, whereas IL6, nitrites, and MDA were similar. Valine was higher in male AF, whereas several acylcarnitines were sexually different, suggesting a mitochondrial involvement in establishing sex differences. Female AFCs displayed higher expression of ERα protein and a higher ERα/ERß ratio. The ratio of LC3II/I, an index of autophagy, was higher in female AFCs, while LC3 gene was similar in both sexes. No significant sex differences were found in the expression of the lysosomal protein LAMP1, while p62 was higher in male AFCs. LAMP1 gene was upregulated in male AFCs, while p62 gene was upregulated in female ones. Finally, caspase 9 activity and senescence linked to telomeres were higher in female AFCs, while caspase 3 and ß-galactosidase activities were similar. This study supports the idea that sex differences start very early in prenatal life and influence specific parameters, suggesting that it may be relevant to appreciate sex differences to cover knowledge gaps. This might lead to improving the diagnosis of risk prediction for pregnancy complications and achieving a more satisfactory monitoring of fetus health, even preventing future diseases in adulthood.

Combined systemic inflammatory indexes as reflectors of outcome in patients with COVID­19 infection admitted to ICU.

INTRODUCTION: The principal etiology of mortality in COVID-19 patients is the systemic pro-inflammatory processes which may lead to acute respiratory distress syndrome. Hematologic indices are reachable representatives of inflammation in patients with COVID-19 infection. The purpose of the current study was to evaluate the potential predictive value of these inflammatory indices in the in-hospital mortality of ICU-admitted COVID-19 patients. The studied indexes included AISI, dNLR, NLPR, NLR, SII, and SIRI. METHOD: 315 COVID-19 patients admitted to ICU managed in Imam Khomeini Hospital of Urmia, Iran, during the last 6 months of 2020 were retrospectively enrolled in the study and divided into two subgroups based on their final outcome, discharge or death. RESULTS: Total leucocyte count (TLC), absolute neutrophil count (NLC), urea, Cr, RDW, AISI, dNLR, NLPR, NLR, SII, and SIRI were drastically elevated in the dead patients (P < 0.05). The optimal cut-off points for AISI (378.81), dNLR (5.66), NLPR (0.03), NLR (5.97), SII (1589.25), and SIRI (2.31) were obtained using ROC curves. NLR and SII had the highest sensitivity (71.4%) and specificity (73.6%), respectively. Patients with above-cut-off levels of ISI, dNLR, NLPR, NLR, and SII had lower average survival time. Age (OR = 1.057, CI95%: 1.030-1.085, p < 0.001) and dNLR (OR = 1.131, CI95%: 1.061-1.206, p < 0.001) were the independent predictors for mortality in the studied COVID-19 patients based on multivariate logistic regression. CONCLUSION: Age and dNLR are valuable predictive factors for in-hospital death of ICU-admitted COVID-19 patients. Besides, other indices, AISI, NLPR, NLR, SII, and SIRI, may have an additional role that requires further investigation.

Predictive value of preoperative inflammatory indexes for postoperative early recurrence of hepatitis B-related hepatocellular carcinoma.

Objective: To investigate the predictive value of preoperative neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), systemic inflammation response index (SIRI), and systemic immune inflammation index (SII) for early recurrence after liver resection in patients with hepatitis B-related hepatocellular carcinoma. Methods: A retrospective study was conducted on 162 patients who underwent hepatitis B-related hepatocellular carcinoma (HCC) resection between January 2013 and April 2016. The Youden index was utilized to calculate the optimal cut-off value. The Pearson Chi-square test was applied to analyze the relationship between inflammatory indexes and common clinical and pathological features. The Kaplan-Meier method and Log-Rank test were implemented to compare the recurrence-free survival rate within 2 years of the population. The Cox regression analysis was used to identify the risk factors for early postoperative recurrence. Results: The best cut-off values of SIRI, PLR, NLR and SII were 0.785, 86.421, 2.231 and 353.64, respectively. Tumor diameter, degree of tumor differentiation, vascular invasion, SIRI>0.785, PLR>86.421, NLR>2.231 and SII>353.64 were risk factors for early recurrence. Combining the above seven risk factors to construct a joint index, the AUC of the joint prediction model was 0.804. The areas under the ROC curves of SIRI, PLR, NLR, and SII were 0.659, 0.725, 0.680, and 0.723, respectively. There was no significant difference in the predictive ability between the single inflammatory index models, but the predictive performance of the joint prediction model was significantly higher than that of the single inflammatory index models. The patients with lower SIRI, PLR, NLR, SII and joint index value had longer recurrence-free survival within 2 years. Conclusion: The joint index CIP, constructed by combining preoperative SIRI, PLR, NLP and SII with pathological features, can better predict the early recurrence of HBV-related HCC patients after surgery, which is beneficial in identifying high-risk patients and assisting clinicians to make better clinical choices.

Prognostic values of the prognostic nutritional index, geriatric nutritional risk index, and systemic inflammatory indexes in patients with stage IIB-III cervical cancer receiving radiotherapy.

Background: Growing evidence suggests that nutritional status and inflammation are associated with survival in various cancers. This study aimed to evaluate the prognostic value of the prognostic nutritional index (PNI), geriatric nutritional risk index (GNRI), and systemic inflammatory indexes (neutrophil/lymphocyte ratio [NLR], monocyte/lymphocyte ratio [MLR], and platelet/lymphocyte ratio [PLR]) in patients with stage IIB-III cervical cancer receiving radiotherapy. Results: The ideal cutoff values for the PNI, GNRI, NLR, MLR, and PLR were 48.3, 97.04, 2.8, 0.41, and 186.67, respectively. Low PNI and GNRI scores were associated with poor OS and PFS. High NLR, MLR, and PLR also predicted inferior 5-year OS and PFS rates in patients with stage IIB-III cervical cancer. Multivariate Cox regression analysis identified tumor size, histological type, stage, number of metastatic lymph nodes, PNI, GNRI, NLR, PLR, and MLR as significant prognostic factors for OS and PFS. Conclusions: The current findings suggest that the PNI, GNRI, NLR, PLR, and MLR are essential parameters for predicting prognosis in patients with stage IIB-III cervical cancer receiving radiotherapy.

Prognostic value of inflammatory and nutritional indexes among advanced NSCLC patients receiving PD-1 inhibitor therapy.

Though immunotherapy has to some extent improved the prognosis of patients with advanced non-small cell lung cancer (NSCLC), only a few patients benefit. Furthermore, immunotherapy efficacy is affected by inflammatory and nutritional status of patients. To investigate whether dynamics of inflammatory and nutritional indexes were associated with prognosis, 223 patients were analysed retrospectively. The inflammatory indexes of interest were neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and systemic immune-inflammation index (SII) while prognostic nutritional index (PNI) and the haemoglobin, albumin, lymphocyte and platelet (HALP) score were considered as nutritional indexes. Patients were divided into high and low groups or into 'increase' and 'decrease' groups based on pre-treatment cut-off values and index dynamics after 6-week follow-up respectively. High pre-treatment PLR (OR = 2.612) and increase in NLR during follow-up (OR = 2.516) were significantly associated with lower objective response rates. Using multivariable analysis, high pre-treatment PLR (HR, 2.319) and increase in SII (HR, 1.731) predicted shorter progression-free survival, while high pre-treatment NLR (HR, 1.635), increase in NLR (HR, 1.663) and PLR (HR, 1.691) and decrease in PNI (HR, 0.611) predicted worse overall survival. The nomogram's C-index in inside validation was 0.718 (95% CI: 0.670-0.766). Our results indicated both nutritional and inflammatory indexes are associated with survival outcomes. Inflammatory indexes were additionally linked to treatment response. Index dynamics are better predictors than baseline values in predicting survival in advanced NSCLC patients receiving PD-1 inhibitor combined with chemotherapy as first-line.

Application Value of Systemic Inflammatory Indexes in the Clinical Evaluation of Patients with Heart Failure with Preserved Ejection Fraction (HFpEF).

Background: In areas where medical resources are scarce, an economical and convenient way to assess patients' condition so that treatment plans can be adjusted in a timely manner makes sense. The clinical value of systemic inflammatory indexes (SII) such as neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), albumin-to-gamma-glutamyl-transferase ratio (AGR), white-blood-cell-count-to-mean-platelet-volume ratio (WMR), high-density-lipoprotein-cholesterol-to-C-reactive-protein ratio (HCR), etc. were explored in heart failure (HF) with preserved ejection fraction (HFpEF) because of their easy availability and clinical value in the diagnosis, therapy and prognosis of cardiovascular diseases. Methods: 189 inpatients (including 48 patients with New York Heart Association (NYHA) I in the control group, and 141 patients with NYHA II-IV in the study group) from The First Affiliated Hospital of Jinan University, during the period July 2018 to March 2022, were included by retrieving electronic medical records. Logistic regression analysis, Spearman's correlation coefficient, operating characteristic curve, etc. were used to analyze the data. Results: In patients with HFpEF, LMR (OR = 0.463, 95% CI 0.348−0.617, p = 0.000), NLR and N-terminal pro-B-type natriuretic peptide (NT-proBNP) were independent predictors for the presence of HF, and LMR (OR = 2.630, 95% CI 2.016−3.435, p = 0.000), NLR, FAG, MHR, AGR and NT-proBNP were independent predictors for increased NYHA functional classification. There were good correlations (r > 0.4) between LMR (r = −0.667, p = 0.000), NLR, WMR, HCR, NT-proBNP (r = −0.681, p = 0.000) and NYHA functional classification, and LMR (AUC = 0.803, 95% CI 0.729−0.849, p = 0.0001), NLR and NT-proBNP (AUC = 0.805, 95% CI 0.738−0.861, p = 0.0001) had good diagnostic values (AUC > 0.7) for HF in patients with HFpEF. In addition, there were certain correlations between LMR, NT-proBNP and echocardiography indicators of cardiac structural. Conclusions: SII have a potential application value in the clinical evaluation of patients with HFpEF in the follow-up, especially in areas with limited medical resources, as they are more convenient and cost effective. Among different SII, LMR is probably the most promising metric. However, large-scale clinical trials are needed in the future to confirm these findings.

A novel quantitative prognostic model for initially diagnosed non-small cell lung cancer with brain metastases.

BACKGROUND: The prognosis of non-small cell lung cancer (NSCLC) with brain metastases (BMs) had been researched in some researches, but the combination of clinical characteristics and serum inflammatory indexes as a noninvasive and more accurate model has not been described. METHODS: We retrospectively screened patients with BMs at the initial diagnosis of NSCLC at Sun Yat-Sen University Cancer Center. LASSO-Cox regression analysis was used to establish a novel prognostic model for predicting OS based on blood biomarkers. The predictive accuracy and discriminative ability of the prognostic model was compared to Adjusted prognostic Analysis (APA), Recursive Partition Analysis (RPA), and Graded Prognostic Assessment (GPA) using concordance index (C-index), time-dependent receiver operating characteristic (td-ROC) curve, Decision Curve Analysis(DCA), net reclassification improvement index (NRI), and integrated discrimination improvement index (IDI). RESULTS: 10-parameter signature's predictive model for the NSCLC patients with BMs was established according to the results of LASSO-Cox regression analysis. The C-index of the prognostic model to predict OS was 0.672 (95% CI = 0.609 ~ 0.736) which was significantly higher than APA,RPA and GPA. The td-ROC curve and DCA of the predictive model also demonstrated good predictive accuracy of OS compared to APA, RPA and GPA. Moreover, NRI and IDI analysis indicated that the prognostic model had improved prediction ability compared with APA, RPA and GPA. CONCLUSION: The novel prognostic model demonstrated favorable performance than APA, RPA, and GPA for predicting OS in NSCLC patients with BMs.

Inflammatory Indexes as Predictive Biomarkers of Postoperative Complications in Oncological Thoracic Surgery.

The role of inflammatory responses in predicting outcomes in oncological thoracic surgery is still unclear. The aim of this study was to evaluate a series of blood count inflammation indexes as predicting factors for postoperative complications. We retrospectively studied 249 patients undergoing elective thoracic surgery in our institution between 2008 and 2020. A total of 184 patients underwent open surgery, and 65 underwent VATS. The neutrophil-to-lymphocyte (NLR), monocyte-to-lymphocyte (MLR), and platelet-to-lymphocyte (PLR) ratios, Systemic Inflammation Response Index (SIRI) were calculated preoperatively and on the first and fourth postoperative days, as well as a new derivative index, the Aggregate Inflammation Systemic Index (AISI). Univariate correlations evidenced a statistically significant association between the NLR at the fourth postoperative day and the occurrence of surgical complications in the global cohort (rho = 0.15, p = 0.03). A similar significant association with MLR on the fourth postoperative day is found in the open group (rho = -0.15, p = 0.048). NLR and LMR on the fourth postoperative day are associated with postoperative complications in the whole and open groups, respectively. Simple, easy-to-perform and inexpensive, blood cell count indexes may be useful in predicting complications in oncological thoracic surgery. A greater number of broader, prospective, randomized studies are necessary to confirm these findings.

Predictive significance of inflammatory indexes in metastatic nonsmall cell lung cancer patients treated with platinum-doublet chemotherapy.

Introduction: Lung cancer is the leading cause of cancer-related deaths, worldwide. Despite immune checkpoint inhibitors and targeted therapy have revolutionized the treatment of metastatic nonsmall cell lung cancer (NSCLC), a significant proportion of patients are still treated with platinum-based chemotherapy. It is widely noticed that systemic inflammation plays an important role in the development and progression of many solid tumors. In this study, we aimed to analyze the predictive role of the systemic immune-inflammation index (SII), neutrophil-to-lymphocyte ratio (NLR), and prognostic nutritional index (PNI) in patients with advanced NSCLC treated with first-line platinum-doublet chemotherapy. Methods: We retrospectively collected data of patients treated with first-line therapy for metastatic NSCLC. All patients were treated with first-line platinum-doublet chemotherapy. The patients were grouped based on the median values of SII, PNI, and NLR. The Mann-Whitney U test was used for comparisons between groups. Results: The chemotherapy response rate (RR) was 75% in all patients. RR is statistically significantly lower in high SII, low PNI, and high NLR groups. Conclusions: High inflammatory indexes in metastatic NSCLC patients who were treated with platinum-doublet chemotherapy are related to low chemotherapy RR.

Inflammatory Indexes for Assessing the Severity and Disease Progression of Ulcerative Colitis: A Single-Center Retrospective Study.

Background: Active and severe ulcerative colitis (UC) and non-response to 5-aminosalicylic acid (5-ASA) are related to poor outcomes and should be accurately identified. Several integrated inflammatory indexes are potentially useful to assess the disease severity in patients with acute or critical diseases but are underexplored in patients with UC. Methods: Patients with UC consecutively admitted to our hospital between January 2015 and December 2020 were retrospectively grouped according to the activity and severity of UC and response to 5-ASA. The neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), systemic immune-inflammation index (SII), neutrophil-to-platelet ratio (NPR), platelet-to-albumin ratio (PAR), C-reactive protein-to-albumin ratio (CAR), and C-reactive protein-to-lymphocyte ratio (CLR) were calculated. The areas under receiver operating characteristic curves (AUC) were calculated. Results: Overall, 187 patients with UC were included, of whom 151 were active, 55 were severe, and 14 were unresponsive to 5-ASA. The active UC group had significantly higher NLR, PLR, SII, and PAR levels. SII had the greatest predictive accuracy for active UC, followed by PLR, PAR, and NLR (AUC = 0.647, 0.641, 0.634, and 0.626). The severe UC group had significantly higher NLR, PLR, SII, PAR, CAR, and CLR levels. CLR had the greatest predictive accuracy for severe UC, followed by CAR, PLR, SII, NLR, and PAR (AUC = 0.732, 0.714, 0.693, 0.669, 0.646, and 0.63). The non-response to the 5-ASA group had significantly higher CAR and CLR levels. CAR had a greater predictive accuracy for non-response to 5-ASA than CLR (AUC = 0.781 and 0.759). Conclusion: SII, CLR, and CAR may be useful for assessing the severity and progression of UC, but remain not optimal.

Expression and clinical significance of miR-204 in patients with hypertensive disorder complicating pregnancy.

OBJECTIVE: Hypertensive disorder complicating pregnancy (HDCP) is a unique and common obstetrical complication in pregnancy. The current study sought to investigate the diagnostic value of serum miR-204 in HDCP patients. METHODS: A total of 196 HDCP patients were enrolled, with 54 healthy pregnant women as controls. The expression levels of miR-204 and inflammatory factors in the serum were determined. Receiver operating characteristic (ROC) curve was used to assess the diagnostic value of miR-204 in HDCP patients. Person coefficient was introduced to analyze the correlation between miR-204 and inflammatory indexes. Kaplan-Meier method was employed to analyze the effect of miR-204 expression on the incidence of adverse pregnancy outcomes. Logistic regression was adopted to assess the risk factors for adverse pregnancy outcomes. RESULTS: miR-204 expression was upregulated in the serum of HDCP patients. The serum miR-204 level > 1.432 could assist the diagnosis of HDCP. miR-204 level in the serum was positively correlated with TNF-α, IL-6, and hs-CRP concentrations in HDCP patients. The risk of adverse outcomes was higher in pregnant women with high miR-204 expression. High miR-204 expression was associated with an increased risk of adverse pregnancy outcomes after adjusting the family history of HDCP, systolic pressure, diastolic pressure, AST, ALT, LDH, 24-h urinary protein, TNF-α, IL-6, and hs-CRP. CONCLUSION: The high expression of miR-204 assists the diagnosis of HDCP and is an independent risk factor for adverse pregnancy outcomes in HDCP patients.

Quantitative Metabolomics to Explore the Role of Plasma Polyamines in Colorectal Cancer.

Colorectal cancer (CRC) is one of the major public health and socio-economic problems, which management demands the development of non-invasive screening tests. Assessment of circulating polyamines could be a valuable tool, although analytical problems still preclude its clinical practice. We exploited ultra-high-resolution liquid chromatography and mass spectrometry, as a highly sensitive and innovative method, to profile eleven polyamines, including spermine and spermidine with their acetylated forms. These data together with an evaluation of the inflammatory indexes might represent suitable biomarkers for the identification of CRC patients. The statistical models revealed good discrimination in distinguishing CRC patients from healthy subjects. The plasma assessment of ornithine and acetylspermine, as well as lymphocyte/platelet ratio, revealed helpful information on the progression of CRC. The combined profiles of circulating polyamines and inflammatory indexes, together with the application of an innovative technology, could represent a valuable tool for discriminating patients from different clinical groups.

Clinical characteristics of 225 patients with bone and joint infection / 中华传染病杂志

Objective:To analyze the clinical characteristics and pathogen distributions of the patients with bone and joint infection.Methods:The clinical data and etiological results of 225 patients with bone and joint infection from January 2008 to October 2020 in Huashan Hospital, Fudan University were retrospectively analyzed.Statistical analysis was conducted by chi-square test.Results:Of the 225 cases with bone and joint infection, 75.6%(170/225) were extremities and other osteomyelitis, 16.0%(36/225) were suppurative arthritis, 8.4%(19/225) were spinal osteomyelitis. Non-implants related infection accounted for 80.4%(181/225) of the cases, while 19.6%(44/225) of the cases were implants related infection. The main clinical manifestations were localized pain (48.4%(109/225)), dyskinesia (47.6%(107/225)), localized swelling (28.9%(65/225)), fever (28.0%(63/225)), and increased purulent exudation (24.9%(56/225)). The proportions of localized pain (55.8%(101/181)) and fever (31.5%(57/181)) of non-implants infection were higher than those of implants infection (18.2%(8/44) and 13.6%(6/44), respectively), while the proportion of increased purulent exudation in implants infection (50.0%(22/44)) was higher than that in non-implants infection (18.8%(34/181)). There were all significant differences between the two groups ( χ2=15.49, 5.60 and 18.45, respectively, all P<0.050). Of the 225 cases, 63 cases(28.0%) had complications with other site infection, especially soft tissue infection and bloodstream infection. A total of 106 strains of pathogens were isolated from 225 specimens, 58.5%(62/106) of them were Gram positive bacterium.Among them, 34.0%(36/106) were Staphylococcus aureus, with the rate of methicillin resistant Staphylococcus aureus (MRSA) isolation accounting for 11.3%(12/106). Laboratory tests showed that 40.4%(91/225) of the patients had elevated erythrocyte sedimentation rate (ESR), 32.9%(74/225) patients had elevated C-reactive protein (CRP). Proportions of patients with elevated ESR (43.6%(79/181)) and CRP (37.6%(68/181)) in non-implants infection were significantly higher than those in implants infection (27.3%(12/44) and 13.6%(6/44), respectively). There were significant differences between the two groups ( χ2=3.94 and 9.19, respectively, P=0.047 and 0.002, respectively). Conclusions:The main clinical manifestations of bone and joint infection are localized pain, dyskinesia, localized swelling, fever and increased purulent exudation. Patients with bone and joint infection are easy to be complicated with soft tissue infection and bloodstream infection, and often accompanied by increased ESR and CRP levels. Gram positive bacterium are the main pathogens.

Prognostic value and association of sarcopenic obesity and systemic inflammatory indexes in patients with hepatocellular carcinoma following hepatectomy and the establishment of novel predictive nomograms.

BACKGROUND: The specific impacts of sarcopenic obesity (SO) on hepatocellular carcinoma (HCC) and the association between SO and systemic inflammation remain unclear. This study aimed to investigate the prognostic value and association of SO and systemic inflammation with outcomes after hepatectomy for HCC and develop novel nomograms based on SO and inflammatory indexes for survival prediction. METHODS: We retrospectively enrolled 452 patients with HCC who underwent radical hepatectomy between January 2012 and March 2015 in Fujian Provincial Hospital as the training cohort. In addition, 275 patients during the same period were enrolled as the external validation cohort. Patients were classified into different groups according to the presence of sarcopenia and obesity. Different inflammation indexes were evaluated to select the best predictor of overall survival (OS) and recurrence-free survival (RFS). Univariate and multivariate logistic regression were performed to investigate the associations between inflammatory indexes and SO. The inflammatory indexes with the highest predictive values and SO were selected for subgroup analyses to establish a novel classification system: the SOLMR grade. SOLMR grades identified in the multivariate Cox analysis were selected to construct novel nomograms for OS and RFS. RESULTS: SO (P<0.001) was an independent risk factor for OS and RFS. The lymphocyte-monocyte ratio (LMR) had the highest areas under the receiver operating characteristic (ROC) curves (AUCs) for OS (P<0.001) and RFS (P<0.001) and was identified as an independent factor of SO (P=0.001). SO and the LMR were selected to establish the SOLMR grade. Multivariate Cox analysis revealed that SOLMR grade was a significant independent predictor of OS (P<0.001) and RFS (P<0.001). Nomograms based on SOLMR grades were generated and accurately predicted 1-, 3- and 5-year OS and RFS in HCC patients. The C-index of the novel nomograms was higher than those of the other conventional staging systems (P<0.001). CONCLUSIONS: Both SO and the LMR were independent risk factors for OS and RFS in HCC patients after hepatectomy. The LMR was an independent factor of SO. The novel nomograms developed from the SOLMR grading system combining SO with the LMR provide good prognostic estimates of the outcomes of HCC patients.

Advanced lung cancer inflammation index and its prognostic value in HPV-negative head and neck squamous cell carcinoma: a multicentre study.

PURPOSE: The aim of this study is to evaluate the prognostic value of pre-treatment advanced lung cancer inflammation index (ALI) in patients with HPV-negative HNSCC undergoing up-front surgical treatment. METHODS: The present multi-centre, retrospective study was performed in a consecutive cohort of patients who underwent upfront surgery with or without adjuvant (chemo)-radiotherapy for head and neck squamous cell carcinoma (HNSCC). Patients were stratified by ALI, and survival outcomes were compared between groups. In addition, the prognostic value of ALI was compared with two other indices, the prognostic nutritional index (PNI) and systemic inflammatory index (SIM). RESULTS: Two hundred twenty-three patients met the inclusion criteria (151 male and 72 female). Overall and progression-free survival were significantly predicted by ALI < 20.4 (HR 3.23, CI 1.51-6.90 for PFS and HR 3.41, CI 1.47-7.91 for OS). Similarly, PNI < 40.5 (HR = 2.43, 95% CI: 1.31-4.51 for PFS and HR = 2.40, 95% CI: 1.19-4.82 for OS) and SIM > 2.5 (HR = 2.51, 95% CI: 1.23-5.10 for PFS and HR = 2.60, 95% CI: 1.19-5.67 for OS) were found to be significant predictors. Among the three indices, ALI < 20.4 identified the patients with the worst 5-year outcomes. Moreover, patients with a combination of low PNI and low ALI resulted to be a better predictor of progression (HR = 5.26, 95% CI: 2.01-13.73) and death (HR = 5.68, 95% CI: 1.92-16.79) than low ALI and low PNI considered alone. CONCLUSIONS: Our results support the use of pre-treatment ALI, an easily measurable inflammatory/nutritional index, in daily clinical practice to improve prognostic stratification in surgically treated HPV-negative HNSCC.