Non-invasive detection of lymphoma with circulating tumor DNA features and protein tumor markers.

Background: According to GLOBOCAN 2020, lymphoma ranked as the 9th most common cancer and the 12th leading cause of cancer-related deaths worldwide. Traditional diagnostic methods rely on the invasive excisional lymph node biopsy, which is an invasive approach with some limitations. Most lymphoma patients are diagnosed at an advanced stage since they are asymptomatic at the beginning, which has significantly impacted treatment efficacy and prognosis of the disease. Method: This study assessed the performance and utility of a newly developed blood-based assay (SeekInCare) for lymphoma early detection. SeekInCare utilized protein tumor markers and a comprehensive set of cancer-associated genomic features, including copy number aberration (CNA), fragment size (FS), end motif, and lymphoma-related virus, which were profiled by shallow WGS of cfDNA. Results: Protein marker CA125 could be used for lymphoma detection independent of gender, and the sensitivity was 27.8% at specificity of 98.0%. After integrating these multi-dimensional features, 77.8% sensitivity was achieved at specificity of 98.0%, while its NPV and PPV were both more than 92% for lymphoma detection. The sensitivity of early-stage (I-II) lymphoma was up to 51.3% (47.4% and 55.0% for stage I and II respectively). After 2 cycles of treatment, the molecular response of SeekInCare was correlated with the clinical outcome. Conclusion: In summary, a blood-based assay can be an alternative to detect lymphoma with adequate performance. This approach becomes particularly valuable in cases where obtaining tissue biopsy is difficult to obtain or inconclusive.

Whole-genome sequencing as an alternative to analyze copy number abnormalities in acute myeloid leukemia and myelodysplastic syndrome.

Copy number aberrations (CNA) are the core determinants for diagnosis, risk stratification and prognosis in acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). In this study, a shallow whole-genome sequencing-based assay, LeukoPrint, was utilized to depict genomic CNA profiles from the bone marrow of 137 newly diagnosed AML/MDS patients. It demonstrated 98.1% concordance of CNA profiles with cytogenetics and/or fluorescence in situ hybridization (FISH). It is advantageous in detecting CNAs of short segments (1 Mb) and from samples with low leukemic cell content, more accurate for describing complex karyotypes and less confounded by subjective bias. LeukoPrint improved the overall diagnostic yield by redefining the risk categories for 16 patients by presenting new information. In summary, LeukoPrint provided an automated, convenient, and cost-effective approach to describe genomic CNA profiles. It brought greater diagnostic yield and risk stratification information by incorporating into the routine cytogenetics based on the CNA-related criteria of standard ELN/IPSS-R guidelines.

[NPM1 High Mutant Allele Burden is an Adverse Prognostic Factor for AML Patients with Mutated NPM1].

OBJECTIVE: To investigate the clinical features, accompanying gene mutation characteristics and prognostic factors of adult patients with acute myeloid leukemia with mutated NPM1 (NPM1+AML). METHODS: Seventy-three patients with newly diagnosed adult NPM1+AML were selected. The mutations of 22 genes were detected by second generation sequencing and 43 fusion genes of AML were detected by real-time fluorescent quantitative PCR. The Kaplan-Meier survival curve and Cox multivariate regression analysis were used to study the prognostic factors. RESULTS: A total of 74 NPM1 site mutations were detected in 73 patients with NPM1+AML. The incidence rates were 92.0% L287fs, 2.7% Q289fs and W288fs, 1.4% L258fs and Q289H, among which 1 patient had 2 NPM1 mutations; the different mutation sites had no effect on the prognosis of NPM1+AML. The median value of NPM1 variant allele frequency (VAF) was 35.4% (1.8%-56.6%). Based on the uppermost quartile of 38.4%, the patients were classified as NPM1 VAF>38.4% (NPM1highAML) and NPM1 VAF≤38.4% (NPM1lowAML). Compared with NPM1lowAML, the early mortality rate was statistically significantly higher (33.3% vs 7.3%, P<0.05), and median EFS (148 d，95%CI 58-238 d vs 372 d，95%CI 264-480 d) (P<0.01) and median OS (179 d 95%CI 6-352 d vs 444 d) (P<0.01) were significantly shorter in NPM1high AML. A total of 126 accompanying gene mutation sites were detected in 87.7% of patients with NPM1+AML. The patients with NRAS gene mutation displayed a higher rate of complete remission (100% vs 58%) (P<0.05) and longer median OS (not reached to 320 d, 95%CI 150-490 d) (P<0.05). The 43 fusion genes were examined in 65 out of 73 cases of NPM1+AML, and in all the patients the fusion gene test was negative. Multivariate analysis showed that NPM1 VAF>38.4% was an independent prognostic factor for EFS (HR=3.1, 95% CI 1.6-6.4, P<0.01) and OS (HR=3.0, 95% CI 1.4-6.2, P<0.01). CONCLUSION: The NPM1 gene mutation in AML patients often is accompanied by other gene mutations, while the coexistence of fusion genes is rare; high NPM1 mutant allele burden is an independent prognostic factor for adult AML patients with mutated NPM1.

The Efficacy of an In-Service Education Program Designed to Enhance the Effectiveness of Physical Restraints.

BACKGROUND: Physical restraints are used to enhance the safety of patients and to avoid injury. However, physical restraints may cause injuries if improperly used or if they are used in the absence of continuous monitoring. Nursing staff who use physical restraints often lack sufficient related knowledge, which may increase the risk to patient safety. PURPOSE: This study investigates the impact of an in-service education program for nursing staff that is designed to improve physical-restraint-related knowledge, attitudes, behaviors, and techniques. METHODS: A pretest-posttest design and a quasi-experimental method were employed to evaluate the effectiveness of the in-service education program. One hundred thirty-six nursing staff from four adult intensive care units (ICUs), including two medical ICUs and two surgical ICUs, in a medical center in central Taiwan were enrolled as participants. The experimental group (EG) and the control group (CG) were composed of patients from one randomly assigned medical ICU and one randomly assigned surgical ICU each. The pretest data on physical-restraint-related knowledge, attitudes, behaviors, and techniques were collected before the in-service education program. The EG received 2 hours of classroom education on guidelines and techniques related to physical restraints. The posttest data for the two groups were collected a month after implementation of the in-service education program. General Estimation Equation was used to measure and analyze the data repeatedly. RESULTS: The posttest scores of the EG for knowledge and technique were significantly higher than the pretest scores (p < .0001). However, the posttest scores of the EG for attitudes and behaviors did not significantly differ from the pretest scores. CONCLUSIONS/IMPLICATIONS FOR PRACTICE: In-service education for physical restraints enhances relevant knowledge and techniques but does not significantly affect attitudes or behaviors. Correct implementation of physical restraints not only promotes the quality of nursing care for patients in the ICU but also reduces the risk of physical-restraint-related complications. This study highlights the importance of changing the thoughts and concepts related to the use of physical restraints within the overall caring strategy of hospitals.

Incidence of and risk factors for infection or colonization of vancomycin-resistant enterococci in patients in the intensive care unit.

The prevalence of vancomycin-resistant enterococci (VRE) colonization or infection in the hospital setting has increased globally. Many previous studies had analysed the risk factors for acquiring VRE, based on cross-sectional studies or prevalent cases. However, the actual incidence of and risk factors for VRE remain unclear. The present study was conducted in order to clarify the incidence of and risk factors for VRE in the intensive care unit (ICU). From 1(st) April 2008 to 31(st) March 2009, all patients admitted to a surgical ICU (SICU) were put on active surveillance for VRE. The surveillance cultures, obtained by rectal swab, were taken on admission, weekly while staying in the SICU, and on discharge from the SICU. A total of 871 patients were screened. Among them, 34 were found to carry VRE before their admission to the SICU, and 47 acquired VRE during their stay in the SICU, five of whom developed VRE infections. The incidence of newly acquired VRE during ICU stay was 21.9 per 1000 patient-days (95% confidence interval [CI], 16.4-29.1). Using multivariate analysis by logistic regression, we found that the length of ICU stay was an independent risk factor for new acquisition of VRE. In contrast, patients with prior exposure to first-generation cephalosporin were significantly less likely to acquire VRE. Strategies to reduce the duration of ICU stay and prudent usage of broad-spectrum antibiotics are the keys to controlling VRE transmission.

Infections occurring during extracorporeal membrane oxygenation use in adult patients.

OBJECTIVE: The application of extracorporeal membrane oxygenation in adults has been increasing, but infections occurring during extracorporeal membrane oxygenation use are rarely described. METHODS: We retrospectively analyzed the prospectively collected data on nosocomial infection surveillance of 334 patients aged 16 years or more undergoing their first extracorporeal membrane oxygenation for more than 48 hours at a university hospital from 1996 to 2007 for respiratory (20.4%) and cardiac (79.6%) support. RESULTS: During a total of 2559 extracorporeal membrane oxygenation days, 55 episodes of infections occurred in 45 patients (13.5%), including 38 bloodstream (14.85 per 1000 extracorporeal membrane oxygenation days), 6 surgical site, 4 respiratory tract, 3 urinary tract, and 4 other infections. Stenotrophomonas maltophilia (16.7%) and Candida species (14.6%) were the predominant blood isolates. In stepwise logistic regression analysis, longer duration of extracorporeal membrane oxygenation use (odds ratio 1.003; 95% confidence interval, 1.001-1.005; P = .004), mechanical complications (odds ratio, 4.849; 95% confidence interval, 1.569-14.991; P = .006), autoimmune disease (odds ratio, 6.997; 95% confidence interval, 1.541-31.766; P = .012), and venovenous mode (odds ratio, 4.473; 95% confidence interval, 1.001-19.977; P = .050) were independently associated with a higher risk for infections during extracorporeal membrane oxygenation use. Overall in-hospital mortality was 68.3%, and its independent risk factors included older age (odds ratio, 1.037; 95% confidence interval, 1.021-1.054; P < .001), neurologic complications (odds ratio, 51.153; 95% confidence interval, 6.773-386.329; P < .001), and vascular complications (odds ratio, 1.922; 95% confidence interval, 1.112-3.320; P < .001), but not infections during extracorporeal membrane oxygenation use. CONCLUSIONS: Bloodstream infection was the most common infection during extracorporeal membrane oxygenation use. Duration of extracorporeal membrane oxygenation, mechanical complications, autoimmune disease, and venovenous mode seemed to be independently associated with infections.