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

Jihui Chen ◽  
Yu Yang ◽  
Huimin Yao ◽  
Shuhong Bu ◽  
Lixia Li ◽  

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.

2021 ◽  
Vol 2021 ◽  
pp. 1-6
Yuwang Bao ◽  
Jianxiong Luo ◽  
Tianxing Yu ◽  
Yang Liu ◽  
Xiaohua Li ◽  

We constructed a prognostic-related risk prediction for patients with lung adenocarcinoma by integrating multiple omics information of lung adenocarcinoma clinical information group and genome and transcriptome. Blood samples and cancer and paracancerous lung tissue samples were collected from 480 patients with lung adenocarcinoma. DNA and RNA sequencing was performed on DNA samples and RNA samples. The first follow-up was carried out 3 months after discharge. Clinical information of patients including age, gender, smoking history, and TNM stage was collected. The Cox proportional hazard model evaluated more than 600 potential SNPs related to the prognosis of lung adenocarcinoma. After LASSO analysis, we obtained 4 SNPs related to the prognosis of lung adenocarcinoma (including rs1059292, rs995343, rs2013335, and rs8078328). Through the Cox proportional hazard model, 260 candidate genes related to the prognosis of lung adenocarcinoma were evaluated. After subsequent analysis, 3 genes related to the prognosis of lung adenocarcinoma (LDHA, SDHC, and TYMS) were obtained. All survived patients were spilt into a high-risk group ( n = 170 ) and a low-risk group ( n = 170 ) according to 4 SNPs and 3 genes related to the prognosis of lung adenocarcinoma. The overall survival rate of patients in the high-risk group was lower than that in the low-risk group. The prognostic risk prediction index constructed by combining clinical information group and genomic and transcriptome characteristics of multiomics information can effectively distinguish the prognosis of patients with lung adenocarcinoma, which will provide effective support for the precise treatment of patients with lung adenocarcinoma.

2021 ◽  
Qiuling Wu ◽  
Chenjing Qian ◽  
Hua Ying ◽  
Fang Liu ◽  
Yaohui Wu ◽  

Abstract PurposeTo investigate the high-risk factors associated with the increased vulnerability for subsequent clinical infection in Carbapenem-resistant Gram-negative bacteria (CR-GNB) colonized hematological malignancies (HMs) patients, and build a statistical model to predict subsequent infection.MethodAll adult HMs patients with positive anal swab culture for CR-GNB between January 2018 and June 2020 were prospectively followed to assess for any subsequent CR-GNB infections and to investigate the risk factors and clinical features of subsequent infection.ResultsA total of 392 HMs patients were enrolled. Of them, 46.7% developed a subsequent clinical infection, and 42 (10.7%) were confirmed infection and 141 (36%) were clinically diagnosed infection. Klebsiella pneumoniae was the dominant species. The overall mortality rate of patients colonized and infected with CR-GNB was 8.6% and 43.7%. A multivariate analysis showed that remission induction chemotherapy, the duration of agranulocytosis, mucositis, and hypoalbuminemia were significant predictors of subsequent infection after CR-GNB colonization. According to our novel risk predictive scoring model, the high-risk group were > 3 times more likely to develop a subsequent infection in comparison with the low-risk group.ConclusionOur risk predictive scoring model can early and accurately predict subsequent infection in HMs patients with CR-GNB colonization. Early administration of CR-GNB-targeted empirical therapy in the high-risk group is strongly recommended to decrease their mortality.

Ehud Chorin ◽  
Matthew Dai ◽  
Eric Shulman ◽  
Lalit Wadhwani ◽  
Roi-Bar-Cohen ◽  

AbstractWe report the change in the QT interval in 84 adult patients with SARS-CoV-2 infection treated with Hydroxychloroquine/Azithromycin combination. QTc prolonged maximally from baseline between days 3 and 4. in 30% of patients QTc increased by greater than 40ms. In 11% of patients QTc increased to >500 ms, representing high risk group for arrhythmia. The development of acute renal failure but not baseline QTc was a strong predictor of extreme QTc prolongation.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4151-4151
Francesca Montanari ◽  
Govind Bhagat ◽  
Venkatraman Seshan ◽  
Sean Clark-Garvey ◽  
Jasmine M. Zain ◽  

Abstract Abstract 4151 Post-transplant lymphoproliferative disorder (PTLD) is a broad spectrum of lymphoproliferative disorders that can occur after solid organ transplant or hematopoietic stem cell transplant. The incidence ranges from 1% to 20% depending on the type of organ graft, the intensity of the immunosuppression and the Epstein-Barr virus (EBV) serostatus. It represents a serious and potentially life threatening complication, with reported mortality rate up to 40–50%. According to the World Health Organization classification system, PTLD are classified as early lesions (EL), polymorphic (p-PTLD), monomorphic (m-PTLD), and Hodgkin-like (HL). Here we analyzed the prognosis and clinical characteristics of 120 patients diagnosed and treated over a 19-year period (from 1990 to 2009). To the best of our knowledge, this is the largest series of PTLD to be reported by a single Institution. The cases were classified as follows: 70 (58.3%) m-PTLD, 34 (28.3%) p-PTLD, 14 (11.7%) EL, and 2 (1.7%) HL. In the m-PTLD group, 59 were of B-cell origin (52 DLBCL, 4 BL, 2 plasmacytoma-like, 1 multiple myeloma and 1 pleural effusion) and 10 were of T/NK cell lineage (4 peripheral T-cell lymphomas, 2 CTCL, 2 HSTCL, 1 T-ALL and 1 NK-cell lymphoma). The age of the patients ranged from 1 to 76 years, with 39 pediatric patients (<16 year old) and 81 adult patients. The EBV status of the PTLD, was determined in 94 cases, 58 (61.7%) were positive and 38 (38.3%) were negative, with no difference between pediatric and adult patients (p=0.11). CD 20 positivity was available in 106 specimens and was highly expressed in our series (87.6%) with no differences between adult and pediatric patients (p=0.4). Approximately half of the patients were diagnosed in stage I or II of disease (44.2%), and the other half in advanced stage III or IV (55.8%) with no substantial differences between adults and pediatrics (p=1). ECOG score 0 or 1 was observed in 2/3 of the patients (67.2%), and it was more frequently observed in pediatrics than in adults (respectively 80% and 61%) but the difference was not statistically significant (p=0.06). Younger age, CD 20 positivity, good ECOG score, platelet and absolute neutrophil count within normal limits correlated with a longer OS (p=0.001, P<0.001, P<0.001, P<0.001 and p=0.003 respectively). PTLD subtype (i.e. EL, pPTLD, mPTLD, HL), gender, decade of diagnosis (1990-1999 vs 2000–2009), organ transplanted, EBV status, anemia, hypoalbuminemia, elevated LDH, extranodal sites involvement, grafted organ involvement, stage at diagnosis did not correlate with the OS in the univariate analysis. Using the recursive partitioning modeling, a new prognostic score was developed: ECOG score (0-1 vs 2–3), age (pediatrics [<16 year old], adults [>= 16 and <60 year old] and elderly [>60 year old]) and CD 20 status (positive vs negative) provided a tree with 5 nodes (figure 1), separating the patients into 4 risk categories. The low-risk group included pediatric patients with ECOG score of 0–1 (median OS not reached); the intermediate-low-risk group included adults with an ECOG score of 0–1 (median OS of 6.8 years); the intermediate-high-risk group included elderly with ECOG score 0–1 or pediatrics and adults with an ECOG score of 2–4 and CD20 positive or n/a (median OS of 1.8 years); the high-risk group included any patient with an ECOG score of 2–4 and CD20 negative, and elderly patients with CD20 positive or n/a (median OS of 1.3 months). In addition, in the group of adult patients with DLBCL PTLD and pPTLD (61 total), we analyzed the impact on OS of Rituximab treatment, as single agent or in combination with chemotherapy, compared to chemotherapy or immunosuppressant tapering alone. OS curves of patients treated with and without Rituximab adjusted by ECOG score, are shown in figure 2. The median OS of patients treated without rituximab with ECOG score 0–1 (18 patients) was 10.5 years, with ECOG 2–4 (13 patients) was 1.5 months compared to a median OS of 2.7 years in the rituximab group with ECOG score 0–1 (19 patients), and 1.2 years in the rituximab group with ECOG score 2–4 (11 patients) (p=0.8). This series proposed a new prognostic model for patients with PTLD, based on ECOG score, age and CD 20 expression. Interestingly, in our series, in a homogeneous population of adult patients with DLBCL and p-PTLD, the use of rituximab as single agent or in combination, compared to chemotherapy and immunosuppression tapering, did not show a survival benefit. Disclosures: O'Connor: Allos Therapeutics, Inc.: Research Funding.

Marta Marí-Almirall ◽  
Clara Cosgaya ◽  
Cristina Pitart ◽  
Joaquim Viñes ◽  
Laura Muñoz ◽  

Abstract Objectives To characterize the clonal spread of carbapenem-resistant Klebsiella pneumoniae and Escherichia coli isolates between different healthcare institutions in Catalonia, Spain. Methods Antimicrobial susceptibility was tested by disc diffusion. MICs were determined by gradient diffusion or broth microdilution. Carbapenemase production was confirmed by lateral flow. PCR and Sanger sequencing were used to identify the allelic variants of resistance genes. Clonality studies were performed by PFGE and MLST. Plasmid typing, conjugation assays, S1-PFGE plus Southern blotting and MinION Oxford Nanopore sequencing were used to characterize resistance plasmids. Results Twenty-nine carbapenem-resistant isolates recovered from three healthcare institutions between January and November 2016 were included: 14 K. pneumoniae isolates from a tertiary hospital in the south of Catalonia (hospital A); 2 K. pneumoniae isolates from a nearby healthcare centre; and 12 K. pneumoniae isolates and 1 E. coli isolate from a tertiary hospital in Barcelona (hospital B). The majority of isolates were resistant to all antimicrobial agents, except colistin, and all were NDM producers. PFGE identified a major K. pneumoniae clone (n = 27) belonging to ST147 and co-producing NDM-1 and CTX-M-15, with a few isolates also harbouring blaOXA-48. Two sporadic isolates of K. pneumoniae ST307 and E. coli ST167 producing NDM-7 were also identified. blaNDM-1 was carried in two related IncR plasmid populations and blaNDM-7 in a conjugative 50 kb IncX3 plasmid. Conclusions We report the inter-hospital dissemination of XDR high-risk clones of K. pneumoniae and E. coli associated with the carriage of small, transferable plasmids harbouring blaNDM genes.

2021 ◽  
Vol 12 (12) ◽  
Ying Zhang ◽  
Wenping Ma ◽  
Wenhua Fan ◽  
Changyuan Ren ◽  
Jianbao Xu ◽  

AbstractGlioma 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.

1993 ◽  
Vol 36 (5) ◽  
pp. 883-896 ◽  
J. Scott Yaruss ◽  
Edward G. Conture

The purpose of the present study was to examine the relationships between second formant (F2) transitions during the sound/syllable repetitions (SSRs) of young children who stutter and their predicted chronicity of stuttering. Subjects were 13 youngsters who stutter, who were divided into two groups based on their predicted chronicity of stuttering as measured by the Stuttering Prediction Instrument (SPI; Riley, 1984): a high-risk group, consisting of 7 boys. (mean age=50.6 months), and a low-risk group, consisting of 5 boys and 1 girl (mean age=48.5 months). Each child was audio/videotape-recorded during a 30-minute conversational interaction with his or her mother. Ten SSRs per child were acoustically analyzed to identify differences in F2 transitions between the repeated (stuttered) and fluent (nonstuttered) portions of the words. Present findings are consistent with those of Stromsta (1965, 1986), who reported that children who stutter produce F2 transitions during stuttering that are nonmeasurable or missing or that differ in direction of movement from fluent transitions. However, there were no significant between-group differences in the frequency of occurrence of these "abnormal" F2 transitions, findings that are apparently inconsistent with Stromsta’s results. The remaining measurable F2 transitions showed no significant between-group differences in the mean differences between stuttered and fluent F2 transitions for onset and offset frequencies, transition extents, and transition rates. Within both groups, significant positive correlations were found between stuttered and fluent F2 transitions for all acoustic measures except for transition durations, which were not significantly correlated for either high-risk or low-risk subjects. Within the low-risk group, stuttered F2 transitions were typically shorter than fluent transitions. Findings were taken to suggest that some elements of sound or segment prolongation may be present within the SSRs of children who stutter and who are considered to be at high risk for continuing to stutter, indicating that further study of selected aspects of F2 transitions during stuttering may provide useful clinical information for predicting the likelihood that a child will continue to stutter.

2021 ◽  
Yongfei He ◽  
Shuqi Zhao ◽  
Zhongliu Wei ◽  
Xin Zhou ◽  
Tianyi Liang ◽  

Abstract BackgroundIn this study, we comprehensively analyzed the relationship between ferroptosis regulator genes (FRGs) and prognosis of hepatocellular carcinoma (HCC), determined the prognostics value of FRGs, established a prediction model, and explored the relationship with immunotherapy for HCC.MethodsThe mRNA transcriptional levels and clinical information of HCC were obtained from The Cancer Genome Atlas (TCGA) database. The 24 FRGs were combined with the differential expression genes (DEGs) of HCC for further analysis. The prognostics values of differential FRGs via the construction of model and validation by the Cox regression analysis.ResultThere were three genes (CARS1, FANCD2, and SLC7A11) were identified as independent risk factors for HCC, and a predictive model was constructed based on CARS1, FANCD2, and SLC7A11. The model showed that the low-risk group HCC patients with a more prolonged overall survival (OS) than the high-risk group (P=0.001). The high-risk group with higher expression of FRGs than the low-risk group. Finally, the relations between FGEs and immune infiltration showed that CARS1, FANCD2, and SLC7A11 had a positive relationship with macrophage infiltration. From these, three genes might be the potential therapeutic targets.ConclusionOur study indicated that CARS1, FANCD2, and SLC7A11 might have potential value for therapeutic strategies as practical and reliable prognostic tools for HCC.

Jianglin Zheng ◽  
Zijie Zhou ◽  
Yue Qiu ◽  
Minjie Wang ◽  
Hao Yu ◽  

Recent studies have demonstrated that long non-coding RNAs (lncRNAs) are implicated in the regulation of tumor cell ferroptosis. However, the prognostic value of ferroptosis-related lncRNAs has never been comprehensively explored in glioma. In this study, the transcriptomic data and clinical information of glioma patients were downloaded from TCGA, CGGA and Rembrandt databases. We identified 24 prognostic ferroptosis-related lncRNAs, 15 of which (SNAI3-AS1, GDNF-AS1, WDFY3-AS2, CPB2-AS1, WAC-AS1, SLC25A21-AS1, ARHGEF26-AS1, LINC00641, LINC00844, MIR155HG, MIR22HG, PVT1, SNHG18, PAXIP1-AS2, and SBF2-AS1) were used to construct a ferroptosis-related lncRNAs signature (FRLS) according to the least absolute shrinkage and selection operator (LASSO) regression. The validity of this FRLS was verified in training (TCGA) and validation (CGGA and Rembrandt) cohorts, respectively. The Kaplan-Meier curves revealed a significant distinction of overall survival (OS) between the high- and low-risk groups. The receiver operating characteristic (ROC) curves exhibited robust prognostic capacity of this FRLS. A nomogram with improved accuracy for predicting OS was established based on independent prognostic factors (FRLS, age, and WHO grade). Besides, patients in the high-risk group had higher immune, stroma, and ESTIMATE scores, lower tumor purity, higher infiltration of immunosuppressive cells, and higher expression of immune checkpoints. Patients in the low-risk group benefited significantly from radiotherapy, while no survival benefit of radiotherapy was observed for those in the high-risk group. In conclusion, we identified the prognostic ferroptosis-related lncRNAs in glioma, and constructed a prognostic signature which was associated with the immune landscape of glioma microenvironment and radiotherapy response.

2019 ◽  
Xiaojun Zhan ◽  
Chandala Chitguppi ◽  
Ethan Berman ◽  
Gurston Nyquist ◽  
Tomas Garzon-Muvdi ◽  

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