Multivariate Cox Proportional Risk Regression Research Articles

Prognostic value and potential molecular mechanism of the like-Sm gene family in early-stage pancreatic ductal adenocarcinoma.

BackgroundThe purpose of this study was to investigate the prognostic significance of like-Sm (LSM) genes in early pancreatic ductal adenocarcinoma (PDAC) and explore the potential molecular mechanism. The protein product of the LSM1 gene is also known as CASM and YJL124C, while that of the LSM4 gene is known as GRP and YER112W.MethodsData from 112 patients attached to the Whipple surgery were collected from the TCGA database of clinical characteristics and survival data. The Kaplan-Meier method and the multivariate Cox proportional risk regression model were used to analyze the impact of LSM genes on outcomes in these 112 patients. We performed gene-gene interaction (GGI) and protein-protein interaction (PPI) analysis to probe interactions between LSM family genes. Bioinformatics techniques were applied to study the potential early-stage molecular mechanisms of LSM genes. Previously, only a few studies have explored the role and potential mechanisms of LSM1 in pancreatic tumor transformation, revealing possible links to transforming growth factor-β, altering the expression of MMP1, uPAR, and SerpinB5 to enhance invasion and metastasis in pancreatic cancer, and facilitating mRNA decapping and degradation. Gene set enrichment analysis (GSEA) also proved that LSM genes are associated with RNA splicing, RNA synthesis, and RNA decomposition, and they may indirectly cause carcinogenesis through other genes such as myc.ResultsThe results showed that LSM1 (adjusted P=0.004) and LSM4 (adjusted P=0.034) were associated with the prognosis of patients with PDAC, and patients with high expression levels of LSM1 (adjusted HR =2.338) or LSM4 (adjusted HR =1.803) tended to experience bad outcomes.ConclusionsOur study revealed that LSM1 and LSM4 might be used as prognostic biomarkers in early PDAC.

Identification and Analysis of Three Hub Prognostic Genes Related to Osteosarcoma Metastasis.

Osteosarcoma (OS) often occurs in children and often undergoes metastasis, resulting in lower survival rates. Information on the complexity and pathogenic mechanism of OS is limited, and thus, the development of treatments involving alternative molecular and genetic targets is hampered. We categorized transcriptome data into metastasis and nonmetastasis groups, and 400 differential RNAs (230 messenger RNAs (mRNAs) and 170 long noncoding RNAs (lncRNAs)) were obtained by the edgeR package. Prognostic genes were identified by performing univariate Cox regression analysis and the Kaplan–Meier (KM) survival analysis. We then examined the correlation between the expression level of prognostic lncRNAs and mRNAs. Furthermore, microRNAs (miRNAs) corresponding to the coexpression of lncRNA-mRNA was predicted, which was used to construct a competitive endogenous RNA (ceRNA) regulatory network. Finally, multivariate Cox proportional risk regression analysis was used to identify hub prognostic genes. Three hub prognostic genes (ABCG8, LOXL4, and PDE1B) were identified as potential prognostic biomarkers and therapeutic targets for OS. Furthermore, transcriptions factors (TFs) (DBP, ESX1, FOS, FOXI1, MEF2C, NFE2, and OTX2) and lncRNAs (RP11-357H14.16, RP11-284N8.3, and RP11-629G13.1) that were able to affect the expression levels of genes before and after transcription were found to regulate the prognostic hub genes. In addition, we identified drugs related to the prognostic hub genes, which may have potential clinical applications. Immunohistochemistry (IHC) and quantitative real-time polymerase chain reaction (qRT-PCR) confirmed that the expression levels of ABCG8, LOXL4, and PDE1B coincided with the results of bioinformatics analysis. Moreover, the relationship between the hub prognostic gene expression and patient prognosis was also validated. Our study elucidated the roles of three novel prognostic biomarkers in the pathogenesis of OS as well as presenting a potential clinical treatment for OS.

Clinical Characteristics and Prognostic Factors of Early-Onset Pancreatic Neuroendocrine Tumors.

Background:The incidence of pancreatic neuroendocrine tumors (PNETs) has increased significantly. The purpose of this study was to analyze the clinical characteristics and prognosis of patients under 50 years old.Methods:Patients with PNETs recorded in the Surveillance, Epidemiology, and End Results (SEER) database from 2004 to 2015 were analyzed. The clinical characteristics were analyzed by Chi-square test. The Kaplan-Meier method was used to estimate overall survival (OS). Multivariate Cox proportional risk regression analysis was used to determine independent prognostic factors.Results:2,303 patients included, of which 547 (23.8%) patients were younger than 50 years old. The number of younger patients has increased steadily, while the proportion in total PNETs decreased recently. Compared with older group, the proportion of the Black, grade I/II, and surgery were higher in early-onset PNETs. Liver was the most frequent metastatic site. There was no significant difference in the incidence of different metastatic sites between younger and older PNETs patients, while younger patients had better OS (P < 0.05). Grade, N stage, M stage, and surgery were independent prognostic factors for OS in early-onset PNETs.Conclusions:Younger patients have unique clinicopathological characteristics compared with older patients in PNETs. Better OS was observed in younger patients which might due to the higher proportion of well-differentiated tumor and surgery than older patients.

Specific Lung Squamous Cell Carcinoma Prognosis-Subtype Distinctions Based on DNA Methylation Patterns.

BackgroundLung squamous cell carcinoma (LUSC) is one of the major types of non-small-cell lung cancer. Epigenetic alterations, such as DNA methylation, have been recognized to be closely associated with the tumorigenesis and progression.Material/MethodsIn this study, we investigated the prognosis subgroups and assessed their correlation with clinical characteristics in LUSC using a methylation array acquired from The Cancer Genome Atlas (TCGA) database.ResultsA total of 196 DNA methylation sites exhibited a significant association with patient prognosis, and patients were further stratified into 7 prognosis subgroups based upon the consensus clustering. The patients in every subgroup were different in terms of prognosis and TNM stage. In addition, we found these 196 significant methylation sites corresponded to 258 genes. The function enrichment analysis revealed that these 258 genes enriched in biological pathways were closely related to cancers, such as DNA methylation and demethylation, cell cycle DNA replication, regulation of signal transduction by p53 class mediator, and genetic imprinting. Subsequently, we determined the levels of methylation sites in 7 subgroups, and found 24 intra-subgroup-specific methylation sites. Meanwhile, we selected 3 subgroups-specific methylation sites to construct the prognosis model for LUSC patients using multivariate Cox proportional risk regression model analysis. This model can effectively predict the prognosis of LUSC patients.ConclusionsOur study identified a new classification of LUSC into 7 prognosis subgroups on the basis of DNA methylation data in TCGA, which demonstrated that molecular subtypes are independent factor for prognosis in LUSC. This may provide a more detailed explanation for LUSC heterogeneity. Additionally, this classification will contribute to discovery of new biomarkers of LUSC and provide more accurate subdivision of LUSC. Furthermore, these specific DNA methylation sites and corresponding genes can serve as biomarkers for early diagnosis, accurate therapy, and prognosis prediction.

Survival status and influencing factors of HIV/AIDS cases in Liuzhou, 2008-2018

Objective: To understand the duration of survival and related influencing factors of HIV/AIDS patients in Liuzhou city. Methods: Both life table method and Kaplan-Meier method were used to calculate the average survival time of HIV/AIDS patients aged ≥15 years reported in Liuzhou city from 2008 to 2018. Factors related to the duration of HIV/AIDS patients were analyzed by univariate and multivariate Cox regression models. Results: A total of 14 856 patients with HIV/AIDS were involved in this study and with the average duration of survival time as 98.74 (95%CI: 97.73-99.75) months. The cumulative survival rates of 1, 3, 5 and 10 years were 77.0%, 72.0%, 68.0%, 61.0% respectively. Results from the multivariate Cox proportional risk regression analysis showed that factors as sex, level of education, age when HIV infection was confirmed, occupation, route of transmission, source of samples, results of the first CD(4) test and antiviral treatment were all related to the duration of survival to the HIV/AIDS patients. Conclusions: Strategies involving early detection of HIV infection, improvement of the CD(4) initial detection rate and early antiviral treatment will help to significantly reduce the risk of death in HIV/AIDS population. Focus should be on male, middle-aged and elderly (over 41 years old), junior high school education or below farmers and migrant worker populations.

Risk analysis of immunological failure of antiretroviral therapy in HIV/AIDS patients in Taizhou prefecture, 2006-2019

Objective: To analyze the immunological failure of antiretroviral therapy (ART), its association with baseline anemia and related factors in HIV/AIDS patients in Taizhou prefecture, during 2006-2019. Methods: A retrospective cohort study was conducted among HIV/AIDS patients under ART. Cox regression model was used to analyze predictors of immunological failure and logistic regression model was used to analyze factors of baseline anemia. Results: A total of 2 904 HIV/AIDS patients were enrolled with a median time of 28 (P(25)-P(75):12-53) months follow-up of ART, in which 177 cases (6.1%) were identified as immunological failure with a failure rate of 2.17 per 100 person-years. The cumulative incidence rates of immunological failure in the first, third, fifth, and tenth years were 5.49%, 6.94%, 7.30% and 8.82%, respectively. Results of multivariate logistic regression analysis showed that for the risk of baseline anemia, ≥66 years old group had 4.17 times higher risk than 18-25 years old group (95%CI: 1.68-10.33), males had 0.67 times higher risk than females (95%CI: 0.50-0.89), and CD(4)(+)T cell counts (CD(4))<200 cells/μl group had 4.35 times higher risk than CD(4)≥350 cells/μl group (95%CI: 2.81-6.72), baseline white blood cells<4.0×10(9) cells/L group had 1.73 times higher risk than 4.0×10(9) cells/L-9.9×10(9) cells/L group (95%CI: 1.31-2.29), baseline platelet counts <100×10(9) cells/L and >300×10(9) cells/L groups had 2.02 times and 4.45 times higher risk than 100×10(9) cells/L-299×10(9) cells/L group (95%CI: 1.36-3.01, 95%CI: 3.05-6.50), respectively. WHO classified stage Ⅲ/Ⅳ group had 2.15 times higher risk than WHO classified stageⅠ/Ⅱ group (95%CI: 1.61-2.87), while heterosexual transmission group had 2.03 times higher risk than homosexual transmission group (95%CI: 1.42-2.92). Results of multivariate cox proportional risk regression showed that for the risk of immunological failure, baseline anemia group had 1.77 times higher risk than no anemia group (95%CI: 1.20-2.60), WHO classified stage Ⅲ/Ⅳ group had 1.66 times higher risk than WHO classified stage Ⅰ/Ⅱ group (95%CI: 1.10-2.48), and withdrawal of follow up and death groups had 3.18 times and 4.61 times higher risks than treatment group (95%CI: 1.96-5.19, 95%CI: 2.98-7.13), respectively. Conclusions: The immunological effect of ART among HIV/AIDS patients in Taizhou prefecture was affected by multiple factors, including anemia, clinical stage and follow-up status. Enhancing surveillance of baseline anemia and timely correction of anemia in elder group can help improve treatment outcome of HIV/AIDS patients.

A novel nomogram to predict survival in patients with recurrent nasopharyngeal carcinoma after salvage endoscopic surgery.

To develop and validate a nomogram to predict survival in patients with recurrent nasopharyngeal carcinoma (NPC) after salvage endoscopic surgery. A total of 229 eligible patients with recurrent NPC were divided into training (n=115) and validation (n=114) cohorts. A multivariate Cox proportional risk regression model was used to identify significant prognostic factors for overall survival (OS) in the training cohort. A nomogram was then developed based on the regression model. The performance of the nomogram was assessed with regard to discrimination and calibration. Patients were divided into low-risk or high-risk groups based on the risk scores derived from the nomogram. Furthermore, decision curve analysis (DCA) was used to assess the clinical utility of the nomogram. Six significant predictors were identified: diabetes mellitus, body mass index (BMI), neutrophil-to-lymphocyte ratio (NLR), T stage, lymph node metastasis, and tumor necrosis. The nomogram incorporating these six predictors demonstrated favorable discrimination and calibration in the training cohort, with a C-index of 0.746 (95% confidence interval [CI] 0.656-0.836), which was subsequently confirmed in the validation cohort (C-index 0.768 [95% CI 0.675-0.861]). Furthermore, the nomogram successfully distinguished patients into low- and high-risk groups. DCA indicated that the nomogram was clinically useful. The novel nomogram demonstrated its potential as an individual tool to predict survival in patients with recurrent NPC after salvage endoscopic surgery.

Investigation of the association between C-X-C motif chemokine receptor subunits and tumor infiltration levels and prognosis in patients with early-stage pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is one of the malignancies with the highest morality rate due to postoperative local invasion and distant metastasis. Although C-X-C motif chemokine receptor (CXCR) subunits have been reported as prognostic indicators in gastric cancer, the prognostic value of CXCR subunits in PDAC remains poorly understood. In the present study, the expression levels and biological functions of CXCR subunits were investigated using multiple publicly accessible bioinformatic platforms and databases. Survival analysis was used to evaluate the prognostic value of CXCR subunits in 112 early-stage PDAC cases by setting the median expression levels as the cut-off values. A nomogram was constructed to combine CXCR subunit expression levels and clinical data for prognosis prediction. Moreover, the association between CXCR subunit expression levels and tumor infiltration levels were detected in PDAC. The expression levels of CXCR subunits were elevated in PDAC tumor tissues. In the multivariate Cox proportional risk regression model, high CXCR2, CXCR4 and CXCR6 expression levels in early-stage PDAC were associated with a more favorable prognosis. Further, it was demonstrated that the differential expression levels of CXCR subunits in PDAC for combined survival analysis could contribute to risk stratification. The nomogram model demonstrated the contribution of CXCR subunits and clinical features in the prognosis of PDAC. Gene Set Enrichment Analysis suggested that CXCR subunits serve a role in immunomodulatory functions. The expression levels and somatic copy number alterations of CXCR subunits were associated with tumor infiltration levels in PDAC. CXCR subunits were associated with prognosis in patients with early-stage PDAC and may be potential drug targets for the treatment of pancreatic cancer.

The Effects of Serum hs-CRP on the Incidence of Lung Cancer in Male Patients with Pulmonary Tuberculosis

This study intended to investigate the effects of serum high-sensitivity C-reactive protein (hs-CRP) on the incidence of lung cancer in male patients with pulmonary tuberculosis. A total of 1091 male patients with pulmonary tuberculosis in Zhejiang Cancer Hospital, Hangzhou, China from Jan 2009 to Jan 2012 were selected as the research objects. All patients were followed up from the beginning of hospitalization. According to serum hs-CRP level, patients were divided into two groups: group A (hs-CRP < 1 mg/L) and group B (hs-CRP > 3 mg/L). The relationship between baseline hs-CRP and the risk of lung cancer in patients with pulmonary tuberculosis was analyzed by multivariate Cox proportional risk regression model, and the serum levels of hs-CRP between lung cancer patients in all groups and other non-lung cancer patients were compared. There were differences in age, drinking, smoking, diabetes history, body mass index (BMI), thyroglobulin (TG), history of hypertension and hyperglycemia among the three groups (P=0.036, 0.018, 0.040, 0.029, 0.006, 0.034, 0.020, 0.010). The serum levels of hs-CRP in patients with squamous carcinoma, adenocarcinoma and small cell carcinoma were significantly higher than those in non-lung cancer patients (P=0.022, 0.043, 0.011). The incidence rates of lung cancer in patients in group B and C were 1.37 and 1.69 times higher than that in group A, respectively. The increased serum level of hs-CRP will increase the incidence rate of lung cancer in male patients with pulmonary tuberculosis.

Prognostic value of combined preoperative fibrinogen-albumin ratio and platelet-lymphocyte ratio score in patients with breast cancer: A prognostic nomogram study

ObjectiveThe purpose of this study was to evaluate the prognostic value of combined preoperative fibrinogen-albumin ratio and platelet-lymphocyte ratio score (FAR-PLR score) in breast cancer, and to establish a nomogram based on the score as well as clinicopathological factors to predict the prognosis of breast cancer. MethodsThe study cohort included 707 breast cancer patients who underwent curative resection in Taizhou Hospital of Zhejiang Province, China from January 2010 to April 2016. FAR and PLR increased by 2 at the same time, only one index increased by 1, and none increased by 0. The relationship of preoperative FAR-PLR score with overall survival time (OS) and disease free survival time (DFS) in breast cancer was analyzed by log-rank test and COX proportional risk regression model, and a nomogram was established based on the results of multivariate analysis. ResultsThe average patient follow-up time was 61.2 months. The FAR-PLR score was conversely correlated with OS and DFS (P < 0.001). In the stage I-II group and III group, the FAR-PLR scores were significantly different among high, medium and low groups of OS and DFS (P < 0.01). FAR-PLR score was also found to be a powerful predictor of prognosis in Luminal B-like subtype, Her-2 overexpression subtype, and triple-negative subtype breast cancers; the higher the FAR-PLR score, the worse the prognosis. Forest charts and multivariate COX proportional risk regression model analysis showed that preoperative FAR-PLR score was an independent risk factor of OS (HR = 1.759, 95%CI = 1.410–2.210, P = 0.000) and DFS (HR = 1.729, 95%CI = 1.385–2.158, P = 0.000) in breast cancer. Based on the COX regression analysis of multiple factors, a nomogram prediction model for the survival of breast cancer was established. The calibration curve analysis indicated that the nomogram results were highly consistent between predicted and actual outcomes. Compared to stage (C-index of OS and DFS were 0.583 and 0.588 respectively), PR (C-index of OS and DFS were 0.592 and 0.592 respectively) and FAR-PLR score (C-index of OS and DFS were 0.592 and 0.591 respectively), the nomogram showed better predictive accuracy (C-index of OS and DFS were 0.652 and 0.651 respectively). ConclusionsThe results of this study suggest that preoperative FAR-PLR score may be a potential new biomarker for predicting survival and prognosis of breast cancer. A prognostic nomogram model based on preoperative FAR-PLR score and clinicopathological factors may help doctors make better clinical decisions for breast cancer treatment.

Adjuvant chemotherapy improves the prognosis of early stage resectable pulmonary large cell carcinoma: analysis of SEER data.

Pulmonary large cell carcinoma (LCC) is a poorly differentiated and rare tumor with dismal outcome, and there are no recommended treatments for LCC. Little is known about the efficacy of postoperative chemotherapy in patients with early stage LCC. The patients with early stage I/II LCC in the Surveillance, Epidemiology and End Results (SEER) database between 2004 and 2015 were retrospectively reviewed. The overall survival (OS) of patients with LCC at different stages and treatments were evaluated by Kaplan-Meier analysis with log-rank test. Univariate and multivariate Cox proportional risk regression analysis were employed to determine the independent risk factors of OS. Finally, a nomogram was constructed to predict the 1 -, 3- and 5-year OS of early stage LCC patients. A total of 1,099 pulmonary LCC cases were included in this study. 71.8% of patients were over 60 years old, and 66.7% of the tumor lesions located in the upper lobe, followed by the lower lobe (25.7%). Meanwhile, the majority of tumors showed poor differentiation (96.1%). The median OS of surgical patients with or without post-operative adjuvant chemotherapy was 61 and 47 months, respectively. Post-operative chemotherapy was associated with better OS (HR: 0.805; 95% CI: 0.676-0.959, P=0.020). For patients with tumor size >3 cm or IB stage tumor, the prognosis of postoperative chemotherapy was better than that of patients without chemotherapy. Multivariate Cox analysis revealed the age, stage and treatments were independent risk factors of OS for early stage LCC. The nomogram had a calibration index of 0.581. The incidence of LCC was high in the elderly, and it generally had poor differentiation. Post-operative chemotherapy is strongly recommended for patients with LCC at stage IB or higher.

Expression of p-AKT and p-mTOR in pediatric Burkitt lymphoma and their correlation with prognosis

Objective: To evaluate the expression of p-AKT and p-mTOR, the key proteins in PI3K/AKT/mTOR pathway in pediatric Burkitt lymphoma (BL), and to investigate the clinical and prognostic significance. Methods: Fifty-eight cases of pediatric BL and thirty cases of reactive hyperplastic lymphadenitis (RH) were collected at Children's Hospital of Fudan University from September 2011 to July 2018. Paraffin sections of tissues were immune stained for p-AKT and p-mTOR, and the expression was assessed and correlated with the clinical features and prognosis. Results: A total of 58 cases were diagnosed and 6 cases lost the follow-up. Of the remaining 52 BL patients including 43 males and 9 females, the median age was 5 years (range: 2 to 14 years). Regarding to the correlation between the two biomarkers, Spearman test showed that p-mTOR was positively associated with the expression of p-AKT (r=0.759, P<0.001). Of all BL patients, the positive rates of p-AKT and p-mTOR were 62.1% (36/58) and 60.3%(35/58) respectively, both significantly higher than control group (P=0.011, P=0.035 respectively). The presence of p-AKT was significantly associated with higher lactate dehydrogenase (LDH≥573 IU/L) level in patients of the disease (P=0.006), while p-mTOR was increased both in the higher LDH and lower ratio of albumin to globulin (A/G) group (P=0.006, P=0.034 respectively). Expression of p-AKT and p-mTOR did not show any statistical correlation with sex, age, St.jude stage, tumor size, B-symptom present or not, number of extra-nodal sites or international prognostic index (IPI) (P>0.05). Fifty-two patients had a median follow-up of 40 months (range: 5-87 months). Univariate analysis showed that p-AKT expression was significant in predicting both inferior OS (5-year estimate, 72.7% vs. 94.7%, χ(2)=4.123, P=0.042) and PFS (5-year estimate, 66.7% vs. 94.7%, χ(2)=5.822, P=0.016). The 5-year OS rate was 71.0% (22/31) for the p-mTOR positive cohort of patients compared to 95.2% (17/21) for p-mTOR negative group (χ(2)=4.881, P=0.027); however, there was no statistical significance in 5-year PFS rate (P>0.05). Especially, the 5-year OS and PFS rate of p-AKT/p-mTOR double-positive group were significantly lower than negative control group (including absence of single p-AKT or p-mTOR expression, and absence of both) (OS: 69.0% vs. 95.7%, χ(2)=6.285, P=0.012; PFS: 65.5% vs. 91.3%, χ(2)=5.405, P=0.020). The results of multivariate COX proportional risk regression analysis indicated that p-AKT/p-mTOR double-positive, higher LDH and IPI score 3-5 were independent prognostic factors for both OS and PFS, and the bulky tumor (>10 cm) for PFS of pediatric BL. Conclusion: The expression of p-AKT and p-mTOR may be a potential reference for diagnosis and the independent prognostic indicators of pediatric BL.

DNA methylation profiling to predict overall survival risk in gastric cancer: development and validation of a nomogram to optimize clinical management.

DNA methylation has been reported to serve an important role in the carcinogenesis and development of gastric cancer. Our aim was to systematically develop an individualized prediction model of the survival risk combing clinical and methylation factors in gastric cancer. A univariate Cox proportional risk regression analysis was used to identify the prognosis-associated methylation sites based on the differentially expressed methylation sites between early and advanced gastric cancer group, then we applied least absolute shrinkage and selection operator (LASSO) Cox regression model to screen candidate methylation sites. Subsequently, multivariate Cox proportional risk regression analysis was conducted to identify predictive signature according to the candidate sites. Relative operating characteristic curve (ROC) analysis manifested that an 11-methylation signature exhibited great predictive efficiency for 1-, 3-, 5-year survival events. Patients in the low-risk group classified according to 11-methylation signature-based risk score yield significantly better survival than that in high-risk group. Moreover, Cox regression analysis combing methylation-based risk score and other clinical factors indicated that 11-methylation signature served as an independent risk factor. The predictive value of risk score was validated in the testing dataset. In addition, a nomogram was constructed and the ROC as well as calibration plots analysis demonstrated the good performance and clinical application of the nomogram. In conclusion, the result suggested the 11-DNA methylation signature may be potentially independent prognostic marker and functioned as a significant tool for guiding the clinical prediction of gastric cancer patients' overall survival.

Clinical significance and prospective molecular mechanism of C‑C motif chemokine receptors in patients with early‑stage pancreatic ductal adenocarcinoma after pancreaticoduodenectomy.

The present study aimed to determine the clinical significance and potential molecular mechanisms of C-C motif chemokine receptor (CCR) genes in patients with early-stage pancreatic ductal adenocarcinoma (PDAC). The transcriptomic, survival and clinical data of 112 patients with early-stage PDAC who underwent pancreaticoduodenectomy were obtained from The Cancer Genome Atlas. The prognostic values of the CCR genes involved in early-stage PDAC were evaluated using Kaplan-Meier analysis and the multivariate Cox proportional risk regression model, and the potential molecular mechanisms were determined using bioinformatics tools. The identified CCRs closely interacted with each other at both the gene and protein levels. High expression levels of CCR5 [adjusted P=0.012; adjusted hazard ration (HR)=0.478, 95% confidence interval (CI)=0.269–0.852], CCR6 (adjusted P=0.026; adjusted HR=0.527, 95% CI=0.299–0.927) and CCR9 (adjusted P=0.001; adjusted HR=0.374, 95% CI=0.209–0.670) were significantly associated with longer overall survival times in patients with early-stage PDAC. The contribution of CCR5, CCR6 and CCR9 to the outcome of early-stage PDAC was also demonstrated. Combined survival analysis of CCR5, CCR6 and CCR9 suggested that patients with high expression levels of these CCRs exhibited the most favorable outcomes. A prognostic signature was constructed in terms of the expression level of CC5, CCR6 and CCR9, and time-dependent receiver operating characteristic curves indicated that this signature was able to effectively predict the outcome of patients with early-stage PDAC. The potential molecular mechanisms of CCR5, CC6 and CCR9 in PDAC include its intersection of the P53, nuclear factor (NF)-κB, generic transcription, mitogen-activated protein kinase and STAT signaling pathways. Collectively, this highlights that CCR5, CCR6 and CCR9 are potential prognostic biomarkers for early-stage PDAC.

Community-Based Management of Child Malnutrition in Zambia: HIV/AIDS Infection and Other Risk Factors on Child Survival.

(1) Background: Supplementary feeding programs (SFPs) are effective in the community-based treatment of moderate acute malnutrition (MAM) and prevention of severe acute malnutrition (SAM); (2) Methods: A retrospective study was conducted on a sample of 1266 Zambian malnourished children assisted from 2012 to 2014 in the Rainbow Project SFPs. Nutritional status was evaluated according to WHO/Unicef methodology. We performed univariate and multivariate Cox proportional risk regression to identify the main predictors of mortality. In addition, a time-to event analysis was performed to identify predictors of failure and time to cure events; (3) Results: The analysis included 858 malnourished children (19 months ± 9.4; 49.9% males). Program outcomes met international standards with a better performance for MAM compared to SAM. Cox regression identified SAM (3.8; 2.1–6.8), HIV infection (3.1; 1.7–5.5), and WAZ <−3 (3.1; 1.6–5.7) as predictors of death. Time to event showed 80% of children recovered by SAM/MAM at 24 weeks. (4) Conclusions: Preventing deterioration of malnutrition, coupled to early detection of HIV/AIDS with adequate antiretroviral treatment, and extending the duration of feeding supplementation, could be crucial elements for ensuring full recovery and improve child survival in malnourished Zambian children.

Pronóstico tras una agudización grave de la EPOC tratada con ventilación mecánica no invasiva

Introduction Patients with chronic obstructive pulmonary disease (COPD) who survived an acute exacerbation with acute respiratory failure that required non-invasive mechanical ventilation (NIMV) are a group with a poor medium-term prognosis. Objective To identify re-admission and mortality rates within one year from discharge and to analyse factors associated with both events in a consecutive series of COPD patients treated with NIMV. Methods A cohort of 93 COPD patients who survived an acute exacerbation and who required NIMV was followed up after discharge. Re-admissions due to respiratory causes and survival were measured and the outcomes were analysed against possible factors associated to such events using multivariate Cox proportional risk regression analysis. Results Over the year following discharge, 61 patients (66%) had to be re-admitted into hospital due to respiratory complications. Upon multivariate analysis, a low FEV 1 value in stable phase and a high average length of stay were associated independently with a high risk of hospital readmission. The probability of survival at 1 year was 0.695. Age, PaCO 2 prior to initiation of NIMV and the number of hospitalisation days in the previous year were associated independently with a high mortality risk. Conclusions This group of COPD patients has a high mortality rate and need for re-hospitalisation in the ensuing year following discharge. The variables relating to the severity of the baseline disease and the actual exacerbation have been shown to be associated with these events, and could be applied to this subgroup of patients in specific follow-up programs.

Prognosis Following Acute Exacerbation of COPD Treated With Non-invasive Mechanical Ventilation

Introduction Patients with chronic obstructive pulmonary disease (COPD) who survived an acute exacerbation with acute respiratory failure that required non-invasive mechanical ventilation (NIMV) are a group with a poor medium-term prognosis. Objective To identify re-admission and mortality rates within one year from discharge and to analyse factors associated with both events in a consecutive series of COPD patients treated with NIMV. Methods A cohort of 93 COPD patients who survived an acute exacerbation and who required NIMV was followed up after discharge. Re-admissions due to respiratory causes and survival were measured and the outcomes were analysed against possible factors associated to such events using multivariate Cox proportional risk regression analysis. Results Over the year following discharge, 61 patients (66 %) had to be re-admitted into hospital due to respiratory complications. Upon multivariate analysis, a low FEV 1 value in stable phase and a high average length of stay were associated independently with a high risk of hospital readmission. The probability of survival at 1 year was 0.695. Age, PaCO 2 prior to initiation of NIMV and the number of hospitalisation days in the previous year were associated independently with a high mortality risk. Conclusions This group of COPD patients has a high mortality rate and need for re-hospitalisation in the ensuing year following discharge. The variables relating to the severity of the baseline disease and the actual exacerbation have been shown to be associated with these events, and could be applied to this subgroup of patients in specific follow-up programs.