Prediction of Prognosis in Adult Patients With Carbapenem-Resistant Klebsiella pneumoniae Infection

ObjectiveCarbapenem-resistant Klebsiella pneumoniae (CRKP) infections are associated with poor patient outcomes. We aimed to analyze the clinical information of adult patients with CRKP infection in order to establish a nomogram for mortality risk as well as to determine the treatment effectiveness of different antimicrobial regimens.MethodsAdult patients diagnosed with CRKP infection in a tertiary hospital in Shanghai between September 2019 and March 2021 were included. The clinical characteristics and clinical outcomes of these patients were analyzed.ResultsA total of 199 cases of CRKP infection were examined. Five factors, namely age ≥65 years, respiratory failure, Sequential Organ Failure Assessment score, serum procalcitonin ≥5 ng/mL, and appropriate treatments in 3 days, were found to be associated with 30-day mortality. Upon incorporating these factors, the nomogram achieved good concordance indexes of 0.85 (95% confidence interval [CI]: 0.80–0.90) and well-fitted calibration curves. Receiver-operating characteristic curves for 7-, 15-, and 30-day survival had areas under the curve of 0.90, 0.87, and 0.88, respectively. Three-drug combination therapy was observed to be associated with lower mortality in the high-risk group (adjusted hazard ratio = 0.24, 95% CI: 0.06–0.99) but not in the low-risk group. Ceftazidime–avibactam, fosfomycin, and amikacin were effective against infections caused by CRKP. Tigecycline improved the treatment efficiency in 7 days, but a trend toward increased mortality was seen (HR, 1.69; 95% CI: 0.98–2.94; P = 0.061).ConclusionThe antimicrobial regimen efficacy data and the predictive nomogram established in this study can help clinicians in identifying high-risk adult patients with CRKP infection, improving the therapeutic effect, and reducing mortality.

CENPF Upregulation is Associated with Immunosuppressive Status and Predicts Poor Clinical Outcomes in Lung Adenocarcinoma Validated by Qrt- PCR

Background: CENPF was differentially expressed in various cancers. However, the relationship between CENPF and immune infiltrates in lung adenocarcinoma was previously unknown.Methods: We implemented a comprehensive analysis of expression of CENPF in the GEO and TCGA databases. CENPF was evaluated for its prognostic value combining clinical samples from the GEPIA2 and TCGA databases. The Metascape together with WebGestalt databases were used for enrichment analysis of genesets that were most postively associated with CENPF. We retrieved the score for immune cell infiltration in TCGA data and examined the correlation between CENPF expression and the infiltration of immune cell by R software.Results: The outcomes exhibited that up-regulated CENPF mRNA expression was evidently related to poor PFS, DSS and OS in patients with lung adenocarcinoma. Moreover, high expression of CENPF was markedly related to genes associated with immune checkpoint. Further analysis showed that T cell CD4+ Th2 infiltration increased in lung adenocarcinoma samples with high CENPF expression.Conclusions: Our study indicated that CENPF led to T cell CD4+ Th2 infiltration through oncogenic activity and may be employed as a biomarker for the prediction of prognosis in lung adenocarcinoma.

RhoA, Claudin 18, and c-MET in Gastric Cancer: Clinicopathological Characteristics and Prognostic Significance in Curative Resected Patients

Background: Recently, markers related to molecular classification were suggested as promising therapeutic targets for treatment and prediction of prognosis in gastric cancer (GC), including c-MET, RhoA, and Claudin-18 (CLDN18). This study aimed to investigate their expression in GC and its correlation with clinicopathological characteristics and survival. Methods: We retrospectively evaluated GC patients who underwent curative gastrectomy. c-MET, RhoA, and CLDN18 were analyzed through immunohistochemistry (IHC), and groups for analysis were determined according to the median values obtained for each marker. Results: Among the 349 GC evaluated, 180 (51.6%), 59 (16.9%), and 61 (17.5%) patients were completely negative for c-MET, RhoA, and CLDN18, respectively. Total gastrectomy, D1 lymphadenectomy, poorly differentiated histology, and greater inflammatory infiltrate were more frequent in the c-MET-negative group. Diffuse type, greater inflammatory infiltrate, and advanced pT and pTNM stage were associated with low-RhoA GC. The venous invasion was more frequent in the low-CLDN18 group. Furthermore, c-MET was positively correlated with RhoA and negatively with CLDN18. HER2 expression was associated with c-MET-positive and high-CLDN18 GC; and loss of E-cadherin expression in c-MET-negative and low-RhoA GC. c-MET-negative and Low-RhoA were significantly associated with worse disease-free survival. Conclusions: c-MET, RhoA, and CLD18 expression occurred frequently in GC. RhoA GC had distinct clinicopathological characteristics related to prognosis. c-MET and RhoA were associated with survival but were not independent predictors of prognosis.

Role of neoadjuvant therapy(chemotherapy and/or radiotherapy) in lymph node and primary rectal tumor regression and prognosis (Preprint)

UNSTRUCTURED Background: Rectal tumors are important malignancies and prediction of prognosis after neoadjuvant therapy is important to improve the prognosis process. The purpose of this study was to determine therole ofneoadjuvant therapy in lymph node regression and primary rectal tumor as well as its association with prognosis. Methods and materials: In this descriptive study, 40 consecutive patients with rectal tumor who were referred toTaleghani Hospital for surgery from 2011 to 2018 were enrolled. Moreover, theneoadjuvant therapy role in lymph node regression and primary rectal tumor was determined as well as its association with prognosis. Results: The results of this study demonstrate that there was no tumor regression in 20% of patients and it wasalso less than 25%, 25-50%, 50-75%, and complete in 22.5%, 35%, 20%, and 2.5% of the patients,respectively. The lymph node regression was complete in 5% of the patients and it wasalso less than 25% in 20% and more than 25% in 50% of them. In addition, it was with no regression in 25% of the patients. The lymph node regression was related to N stage (P=0.018), primary tumor regression grade (P=0.001), yPT (P=0.008), and yPN (P=0.020); however, it was not related to prognosis (P > 0.05). Conclusions: Totally, according to the obtained results, it can be concluded thatneoadjuvant therapy plays a good role in lymph node regression and primary rectal tumor, but it has no association with prognosis. Keywords:Neoadjuvant therapy, Lymph node regression, Primary rectal tumor, Prognosis

Acute Infectious Gastroenteritis: The Causative Agents, Omics-Based Detection of Antigens and Novel Biomarkers

Acute infectious gastroenteritis (AGE) is among the leading causes of mortality in children less than 5 years of age worldwide. There are many causative agents that lead to this infection, with rotavirus being the commonest pathogen in the past decade. However, this trend is now being progressively replaced by another agent, which is the norovirus. Apart from the viruses, bacteria such as Salmonella and Escherichia coli and parasites such as Entamoeba histolytica also contribute to AGE. These agents can be recognised by their respective biological markers, which are mainly the specific antigens or genes to determine the causative pathogen. In conjunction to that, omics technologies are currently providing crucial insights into the diagnosis of acute infectious gastroenteritis at the molecular level. Recent advancement in omics technologies could be an important tool to further elucidate the potential causative agents for AGE. This review will explore the current available biomarkers and antigens available for the diagnosis and management of the different causative agents of AGE. Despite the high-priced multi-omics approaches, the idea for utilization of these technologies is to allow more robust discovery of novel antigens and biomarkers related to management AGE, which eventually can be developed using easier and cheaper detection methods for future clinical setting. Thus, prediction of prognosis, virulence and drug susceptibility for active infections can be obtained. Case management, risk prediction for hospital-acquired infections, outbreak detection, and antimicrobial accountability are aimed for further improvement by integrating these capabilities into a new clinical workflow.

Comprehensive transcriptomic characterization reveals core genes and module associated with immunological changes via 1619 samples of brain glioma

Glioma is the most common primary malignant brain tumor with limited treatment options and poor prognosis. To investigate the potential relationships between transcriptional characteristics and clinical phenotypes, we applied weighted gene co-expression network analysis (WGCNA) to construct a free-scale gene co-expression network yielding four modules in gliomas. Turquoise and yellow modules were positively correlated with the most malignant glioma subtype (IDH-wildtype glioblastomas). Of them, genes in turquoise module were mainly involved in immune-related terms and were regulated by NFKB1, RELA, SP1, STAT1 and STAT3. Meanwhile, genes in yellow module mainly participated in cell-cycle and division processes and were regulated by E2F1, TP53, E2F4, YBX1 and E2F3. Furthermore, 14 genes in turquoise module were screened as hub genes. Among them, five prognostic hub genes (TNFRSF1B, LAIR1, TYROBP, VAMP8, and FCGR2A) were selected to construct a prognostic risk score model via LASSO method. The risk score of this immune-related gene signature is associated with clinical features, malignant phenotype, and somatic alterations. Moreover, this signature showed an accurate prediction of prognosis across different clinical and pathological subgroups in three independent datasets including 1619 samples. Our results showed that the high-risk group was characterized by active immune-related activities while the low-risk group enriched in neurophysiological-related pathway. Importantly, the high-risk score of our immune signature predicts an enrichment of glioma-associated microglia/macrophages and less response to immune checkpoint blockade (ICB) therapy in gliomas. This study not only provides new insights into the molecular pathogenesis of glioma, but may also help optimize the immunotherapies for glioma patients.

Identification of transcriptomics biomarkers for the early prediction of the prognosis of septic shock from pneumopathies

Background Identifying the biological subclasses of septic shock might provide specific targeted therapies for the treatment and prognosis of septic shock. It might be possible to find biological markers for the early prediction of septic shock prognosis. Methods The data were obtained from the Gene Expression Omnibus databases (GEO) in NCBI. GO enrichment and KEGG pathway analyses were performed to investigate the functional annotation of up- and downregulated DEGs. ROC curves were drawn, and their areas under the curves (AUCs) were determined to evaluate the predictive value of the key genes. Results 117 DEGs were obtained, including 36 up- and 81 downregulated DEGs. The AUC for the MME gene was 0.879, as a key gene with the most obvious upregulation in septic shock. The AUC for the THBS1 gene was 0.889, as a key downregulated gene with the most obvious downregulation in septic shock. Conclusions The upregulation of MME via the renin-angiotensin system pathway and the downregulation of THBS1 through the PI3K–Akt signaling pathway might have implications for the early prediction of prognosis of septic shock in patients with pneumopathies.

Status Epilepticus Mortality Risk Factors and a Correlation Survey with the Newly Modified STESS

Background: Status epilepticus (SE) is a neurological emergency and is usually associated with significant morbidity and mortality rates. Several clinical scales have been proposed to predict the clinical outcome of such incidents, including the Status Epilepticus Severity Score (STESS), the modified STESS (mSTESS), and the Encephalitis-Nonconvulsive Status Epilepticus-Diazepam Resistance-Image Abnormalities-Tracheal intubation (END-IT). Nevertheless, there is still a need for a more practical and precise predictive scale. Methods: This is a retrospective cohort study which examines data from patients with SE in our Department of Neurology between 2009 and 2020. Based on the outcome of each case, the patients were divided into survivor and non-survivor groups. We analyzed the independent factors and adjusted the STESS to achieve a better prediction of prognosis. The predictive accuracy of our new STESS scale was then compared with that of the mSTESS and the END-IT. Results: Data on a total of 59 patients were collected, with 6 of them classified as non-survivors. The effects of the variables of age, sex, underlying disease(s), and type(s) of antiepileptic drug (AED) use showed no significant differences between the survivor and non-survivor groups. Importantly, the number of AEDs used in the first week and the use of thiobarbiturates predicted non-survival. We adjusted the STESS to create the newly modified STESS (nSTESS), which showed a better predictive capacity than the STESS, the mSTESS, and the END-IT. Conclusions: Our adjustment of the STESS with the addition of the factors “number of AEDs within the first week” and “use of thiobarbiturates”, could have a positive impact on the prediction of mortality rates compared with currently used scales. This nSTESS could potentially be useful in clinical practices, for the early prediction of outcomes for patients with SE.

Optimal value of CA19-9 determined by KRAS-mutated circulating tumor DNA contributes to the prediction of prognosis in pancreatic cancer patients

Despite the acceptance of carbohydrate antigen 19-9 (CA19-9) as a valuable predictor for the prognosis of pancreatic ductal adenocarcinoma (PDAC), its cutoff value remains controversial. Our previous study showed a significant correlation between CA19-9 levels and the presence of KRAS-mutated ctDNA in the blood of patients with PDAC. Based on this correlation, we investigated the optimal cutoff value of CA19-9 before surgery. Continuous CA19-9 values and KRAS-mutated ctDNAs were monitored in 22 patients with unresectable PDAC who underwent chemotherapy between 2015 and 2017. Receiver operating characteristic curve analysis identified 949.7 U/mL of CA19-9 as the cutoff value corresponding to the presence of KRAS-mutated ctDNA. The median value of CA19-9 was 221.1 U/mL. Subsequently, these values were verified for their prognostic values of recurrence-free survival (RFS) and overall survival (OS) in 60 patients who underwent surgery between 2005 and 2013. Multivariate analysis revealed that 949.7 U/mL of CA19-9 was an independent risk factor for OS and RFS in these patients (P = 0.001 and P = 0.010, respectively), along with lymph node metastasis (P = 0.008 and P = 0.017), unlike the median CA19-9 level (P = 0.150 and P = 0.210). The optimal CA19-9 level contributes to the prediction of prognosis in patients with PDAC before surgery.