Tag: nevin manimala

Folia Microbiol (Praha). 2022 Jun 6. doi: 10.1007/s12223-022-00980-7. Online ahead of print.

ABSTRACT

Next-generation sequencing methods provide comprehensive data for the analysis of structural and functional analysis of the genome. The draft genomes with low contig number and high N50 value can give insight into the structure of the genome as well as provide information on the annotation of the genome. In this study, we designed a pipeline that can be used to assemble prokaryotic draft genomes with low number of contigs and high N50 value. We aimed to use combination of two de novo assembly tools (SPAdes and IDBA-Hybrid) and evaluate the impact of this approach on the quality metrics of the assemblies. The followed pipeline was tested with the raw sequence data with short reads (< 300) for a total of 10 species from four different genera. To obtain the final draft genomes, we firstly assembled the sequences using SPAdes to find closely related organism using the extracted 16 s rRNA from it. IDBA-Hybrid assembler was used to obtain the second assembly data using the closely related organism genome. SPAdes assembler tool was implemented using the second assembly, produced by IDBA-hybrid as a hint. The results were evaluated using QUAST and BUSCO. The pipeline was successful for the reduction of the contig numbers and increasing the N50 statistical values in the draft genome assemblies while preserving the coverage of the draft genomes.

PMID:35668290 | DOI:10.1007/s12223-022-00980-7

Cancer Prev Res (Phila). 2022 Jun 6:OF1-OF11. doi: 10.1158/1940-6207.CAPR-21-0601. Online ahead of print.

ABSTRACT

The microbiome has increasingly been linked to cancer. Little is known about the lung and oral cavity microbiomes in smokers, and even less for electronic cigarette (EC) users, compared with never-smokers. In a cross-sectional study (n = 28) of smokers, EC users, and never-smokers, bronchoalveolar lavage and saliva samples underwent metatranscriptome profiling to examine associations with lung and oral microbiomes. Pairwise comparisons assessed differentially abundant bacteria species. Total bacterial load was similar between groups, with no differences in bacterial diversity across lung microbiomes. In lungs, 44 bacteria species differed significantly (FDR < 0.1) between smokers/never-smokers, with most decreased in smokers. Twelve species differed between smokers/EC users, all decreased in smokers of which Neisseria sp. KEM232 and Curvibacter sp. AEP1-3 were observed. Among the top five decreased species in both comparisons, Neisseria elongata, Neisseria sicca, and Haemophilus parainfluenzae were observed. In the oral microbiome, 152 species were differentially abundant for smokers/never-smokers, and 17 between smokers/electronic cigarette users, but only 21 species were differentially abundant in both the lung and oral cavity. EC use is not associated with changes in the lung microbiome compared with never-smokers, indicating EC toxicity does not affect microbiota. Statistically different bacteria in smokers compared with EC users and never-smokers were almost all decreased, potentially due to toxic effects of cigarette smoke. The low numbers of overlapping oral and lung microbes suggest that the oral microbiome is not a surrogate for analyzing smoking-related effects in the lung.

PREVENTION RELEVANCE: The microbiome affects cancer and other disease risk. The effects of e-cig usage on the lung microbiome are essentially unknown. Given the importance of lung microbiome dysbiosis populated by oral species which have been observed to drive lung cancer progression, it is important to study effects of e-cig use on microbiome.

PMID:35667088 | DOI:10.1158/1940-6207.CAPR-21-0601

Blood. 2022 Jun 6:blood.2022016308. doi: 10.1182/blood.2022016308. Online ahead of print.

ABSTRACT

Evidence of effectiveness of prophylactic use of tranexamic acid (TXA) in thrombocytopenia is lacking. To determine whether TXA safely reduces bleeding incidence in patients undergoing treatment for hematologic malignancies, a randomized double blind clinical trial was conducted June 2016 through June 2020. Of 3120 screened adults 356 patients were eligible and enrolled, and 337 patients (mean age, 53.9; 141 (41.8%) women), randomized to 1,300mg TXA orally or 1,000mg TXA intravenously (n=168) versus placebo (n=169) thrice daily for maximum 30 days. 330 patients were activated when their platelet counts fell below 30,000/µl; 279 (83%) had complete outcome ascertainment. WHO grade 2 or higher bleeding was observed in the 30 days following activation in 50.3% (73/145) and 54.2% (78/144) of patients in the TXA and placebo groups, adjusted odds ratio: 0.83 (95%CI:0.50,1.34; p=0.44). There was no statistically significant difference in mean number of platelet transfusions (0.1;95%CI:-1.9,2.0), mean days alive without grade 2 or higher bleeding (0.8;95%CI:-0.4,2.0), thrombotic events (6/163 (3.7%) TXA, 9/163 (5.5%) placebo), or deaths due to serious bleeding. Most common adverse events were: diarrhea [(116/164 (70.7%) TXA and 114/163 (69.9%) placebo)]; febrile neutropenia [111/164 (67.7%) TXA, 105/163 (64.4%) placebo]; fatigue [106/164 (64.6%) TXA, 109/163 (66.9%) placebo]; and nausea [104/164 (63.4%) TXA, 97/163 (59.5%) placebo]. Among patients with hematologic malignancy undergoing chemotherapy or hematopoietic stem cell transplantation, prophylactic treatment with tranexamic acid compared with placebo did not significantly reduce the risk of WHO grade 2 or higher bleeding. Trial Registration: Clinicaltrials.gov Identifier: NCT02578901.

PMID:35667085 | DOI:10.1182/blood.2022016308

Am J Drug Alcohol Abuse. 2022 Jun 6:1-12. doi: 10.1080/00952990.2022.2072223. Online ahead of print.

ABSTRACT

BACKGROUND: There is a striking geographic variation in drug overdose deaths without a specific drug recorded, many of which likely involve opioids. Knowledge of the reasons underlying this variation is limited.

OBJECTIVES: We sought to understand the role of medicolegal death investigation (MDI) systems in unclassified drug overdose mortality.

METHODS: This is an observational study of 2014 and 2018 fatal drug overdoses and U.S. county-level MDI system type (coroner vs medical examiner). Mortality data are from the CDC’s National Center for Health Statistics. We estimated multivariable logistic regressions to quantify associations between MDI system type and several outcome variables: whether the drug overdose was unclassified and whether involvement of any opioid, synthetic opioid, methadone, and heroin was recorded (vs unclassified), for 2014 (N = 46,996) and 2018 (N = 67,359).

RESULTS: In 2018, drug overdose deaths occurring in coroner counties were almost four times more likely to be unclassified (OR 3.87, 95% CI 2.32, 6.46) compared to medical examiner counties. These odds ratios are twice as large as in 2014 (difference statistically significant, P < .001), indicating that medical examiner counties are improving identification of opioids in drug overdoses faster than coroner counties.

CONCLUSIONS: Accurate reporting of drug overdose deaths depends on MDI systems. When developing state policies and local interventions aimed to decrease opioid overdose mortality, decision-makers should understand the role their MDI system is playing in underestimating the extent of the opioid overdose crisis. Improvements to state and county MDI systems are desirable if accurate reporting and appropriate policy response are to be achieved.

PMID:35667084 | DOI:10.1080/00952990.2022.2072223

J Pediatr Orthop. 2022 Jul 1;42(6):e696-e700. doi: 10.1097/BPO.0000000000002136. Epub 2022 Mar 10.

ABSTRACT

BACKGROUND: Understanding differences between types of study design (SD) and level of evidence (LOE) are important when selecting research for presentation or publication and determining its potential clinical impact. The purpose of this study was to evaluate interobserver and intraobserver reliability when assigning LOE and SD as well as quantify the impact of a commonly used reference aid on these assessments.

METHODS: Thirty-six accepted abstracts from the Pediatric Orthopaedic Society of North America (POSNA) 2021 annual meeting were selected for this study. Thirteen reviewers from the POSNA Evidence-Based Practice Committee were asked to determine LOE and SD for each abstract, first without any assistance or resources. Four weeks later, abstracts were reviewed again with the guidance of the Journal of Bone and Joint Surgery (JBJS) LOE chart, which is adapted from the Oxford Centre for Evidence-Based Medicine. Interobserver and intraobserver reliability were calculated using Fleiss’ kappa statistic (k). χ2 analysis was used to compare the rate of SD-LOE mismatch between the first and second round of reviews.

RESULTS: Interobserver reliability for LOE improved slightly from fair (k=0.28) to moderate (k=0.43) with use of the JBJS chart. There was better agreement with increasing LOE, with the most frequent disagreement between levels 3 and 4. Interobserver reliability for SD was fair for both rounds 1 (k=0.29) and 2 (k=0.37). Similar to LOE, there was better agreement with stronger SD. Intraobserver reliability was widely variable for both LOE and SD (k=0.10 to 0.92 for both). When matching a selected SD to its associated LOE, the overall rate of correct concordance was 82% in round 1 and 92% in round 2 (P<0.001).

CONCLUSION: Interobserver reliability for LOE and SD was fair to moderate at best, even among experienced reviewers. Use of the JBJS/Oxford chart mildly improved agreement on LOE and resulted in less SD-LOE mismatch, but did not affect agreement on SD.

LEVEL OF EVIDENCE: Level II.

PMID:35667059 | DOI:10.1097/BPO.0000000000002136

J Pediatr Orthop. 2022 Jul 1;42(6):e565-e569. doi: 10.1097/BPO.0000000000002137. Epub 2022 Mar 10.

ABSTRACT

BACKGROUND: A subset of patients successfully treated for developmental dysplasia of the hip (DDH) as infants have symptomatic acetabular dysplasia at skeletal maturity leading to periacetabular osteotomy (PAO). The purpose of this study was to compare femoral and acetabular morphology in PAO patients with late acetabular dysplasia after previous treatment for DDH with PAO patients who do not have a history of DDH treatment.

METHODS: A single surgeon’s patients who underwent PAO between 2011 and 2021 were retrospectively reviewed. Patients previously treated for infantile DDH with a Pavlik harness, abduction brace, closed reduction and spica casting, or open reduction and spica casting were included. Patients with previous bony hip surgery were excluded. Preoperative radiographic measurements of each hip were recorded including lateral center edge angle, anterior center edge angle, and Femoro-Epiphyseal Acetabular Roof index. Computed tomography measurements included the coronal center edge angle, sagittal center edge angle, Tönnis angle, acetabular anteversion at 1, 2, and 3 o’clock, femoral neck-shaft angle, femoral version, and alpha angle. Control PAO cases without a history of DDH diagnosis or treatment were matched with the infantile DDH treatment group in a 2:1 ratio based on coronal center edge angle, age, and sex.

RESULTS: There were 21 hips in 18 patients previously treated for infantile DDH (13 patients Pavlik harness, 3 abduction brace, 1 closed reduction, and 1 open reduction). The control PAO cohort was 42 hips in 42 patients who did not have previous DDH treatment. There was no statistically significant difference in any of the recorded measurements between patients previously treated for DDH and those without previous treatment including femoral version (P=0.494), anteversion at 1 o’clock (P=0.820), anteversion at 2 o’clock (P=0.584), anteversion at 3 o’clock (P=0.137), neck-shaft angle (P=0.612), lateral center edge angle (P=0.433), Femoro-Epiphyseal Acetabular Roof index (P=0.144), and alpha angle (P=0.156).

CONCLUSIONS: Femoral and acetabular morphology is similar between PAO patients with persistent symptomatic acetabular dysplasia following DDH treatment and patients presenting after skeletal maturity with acetabular dysplasia and no previous history of DDH treatment.

LEVEL OF EVIDENCE: Level III-case-control, prognostic study.

PMID:35667051 | DOI:10.1097/BPO.0000000000002137

Blood. 2022 Jun 6:blood.2021015173. doi: 10.1182/blood.2021015173. Online ahead of print.

ABSTRACT

To determine the survival benefit of allogeneic hematopoietic cell transplantation (allo-HCT) in chronic myelomonocytic leukemias (CMML), we assembled a retrospective cohort of CMML patients aged 18-70 years diagnosed between 2000 and 2014 from an International CMML Dataset (ICD, n=730) and from the EBMT registry (n=384). The prognostic impact of allo-HCT was analyzed through univariable and multivariable time-dependent models and with a multi-state model, accounting for age, sex, CMML prognostic scoring system (CPSS low and intermediate-1: lower-risk, intermediate-2 and high: higher-risk) at diagnosis, and AML transformation. In univariable analysis, lower-risk CMMLs had a 5-year OS of 20% (95%CI 12-33%) with allo-HCT versus 42% (95%CI 35-49%) without allo-HCT (P<0.001). In higher-risk patients, 5-year OS was 27% (95%CI 21-34%) with allo-HCT versus 15% (95%CI 11-22%) without allo-HCT (P=0.13). With multi-state models, performing allo-HCT before AML transformation reduced overall survival in patients with lower risk CMML while a survival benefit was predicted for men with higher risk CMML. In a multivariable analysis of lower-risk patients, performing allo-HCT before transformation to AML significantly increased the risk of death within two years of transplantation (HR=3.19, 95%CI 2.30-4.42, P<0.001), with no significant change in long-term survival beyond this time point (HR=0.98, 95%CI 0.58-1.64, P=0.92). In higher risk patients, allo-HCT significantly increased the risk of death in the first two years after transplant (HR=1.46, 95%CI 1.09-1.96, P=0.01), but not beyond (HR=0.60, 95%CI 0.34-1.08, P=0.09). Performing allo-HCT before AML transformation decreases life expectancy in lower risk patients but may be considered in higher risk patients.

PMID:35667047 | DOI:10.1182/blood.2021015173

J Pediatr Orthop. 2022 Jul 1;42(6):e559-e564. doi: 10.1097/BPO.0000000000002151. Epub 2022 Mar 22.

ABSTRACT

BACKGROUND: Clinical and administrative registries provide large volumes of data that can be used for clinical research. However, there are several limitations relating to the quality, consistency, and generalizability of big data. In this study, we aim to compare reported demographics and certain outcomes in patients undergoing posterior spinal fusion (PSF) for adolescent idiopathic scoliosis (AIS), neuromuscular scoliosis (NS), and Scheuermann kyphosis (SK) between 3 commonly utilized databases in pediatric orthopaedic research.

METHODS: We used International Classification of Diseases, Ninth Revision (ICD-9), International Classification of Diseases, 10th Revision (ICD-10), and Current Procedural Terminology (CPT) codes to identify patients in the National Surgical Quality Improvement Program (NSQIP), Healthcare Cost and Utilization Project (HCUP), and Pediatric Health Information System (PHIS) between the ages of 10 to 18 that underwent PSF for AIS, SK, and NS from 2012 to 2015. We compared various demographic factors, such as sex, race/ethnicity, age, and rates of postsurgical infection and 30-day readmissions. Data was analyzed with descriptive and univariate statistics.

RESULTS: We identified 9891 patients that underwent PSF in NSQIP, 10,771 patients in PHIS, and 4335 patients in HCUP over the study period. There were significant differences in patient demographics, readmission rates, and infection rates between all patients that underwent PSF across the databases (P<0.01), as well as specifically in patients with AIS (P<0.01). HCUP had the highest proportion of Hispanic patients that underwent PSF (13.5%), as well as patients who had AIS (13.3%) or NS (17.9%). The PHIS database had the highest proportion of patients undergoing PSF for SK. Among patients with NS, there were significant differences in race across the databases (P<0.01), but no significant differences in sex, ethnicity, or readmission (P>0.05). In addition, there were significant differences in race (P=0.04) and readmission (P=0.01) across databases for patients with SK, but no differences in sex or ethnicity (P>0.05). NSQIP reported the highest rate of 30-day readmissions for patients undergoing PSF (17.9%) compared with other databases (HCUP 4.1%, PHIS 12.1%).

CONCLUSIONS: There are significant differences in patient demographics, sample sizes, and rates of complications for pediatric patients undergoing PSF across 3 commonly utilized US administrative databases. Given the variability in reported outcomes and demographics, generalizability is difficult to extrapolate from these large data sources. In addition, certain databases should be selected to appropriately power studies focusing on particular patient populations or outcomes.

PMID:35667050 | DOI:10.1097/BPO.0000000000002151

Brief Bioinform. 2022 Jun 7:bbac227. doi: 10.1093/bib/bbac227. Online ahead of print.

ABSTRACT

In recent work, researchers have paid considerable attention to the estimation of causal effects in observational studies with a large number of covariates, which makes the unconfoundedness assumption plausible. In this paper, we review propensity score (PS) methods developed in high-dimensional settings and broadly group them into model-based methods that extend models for prediction to causal inference and balance-based methods that combine covariate balancing constraints. We conducted systematic simulation experiments to evaluate these two types of methods, and studied whether the use of balancing constraints further improved estimation performance. Our comparison methods were post-double-selection (PDS), double-index PS (DiPS), outcome-adaptive LASSO (OAL), group LASSO and doubly robust estimation (GLiDeR), high-dimensional covariate balancing PS (hdCBPS), regularized calibrated estimators (RCAL) and approximate residual balancing method (balanceHD). For the four model-based methods, simulation studies showed that GLiDeR was the most stable approach, with high estimation accuracy and precision, followed by PDS, OAL and DiPS. For balance-based methods, hdCBPS performed similarly to GLiDeR in terms of accuracy, and outperformed balanceHD and RCAL. These findings imply that PS methods do not benefit appreciably from covariate balancing constraints in high-dimensional settings. In conclusion, we recommend the preferential use of GLiDeR and hdCBPS approaches for estimating causal effects in high-dimensional settings; however, further studies on the construction of valid confidence intervals are required.

PMID:35667004 | DOI:10.1093/bib/bbac227

J Clin Oncol. 2022 Jun 6:JCO2101393. doi: 10.1200/JCO.21.01393. Online ahead of print.

ABSTRACT

PURPOSE: High levels of circulating tumor plasma cells (CTC-high) in patients with multiple myeloma are a marker of aggressive disease. We aimed to confirm the prognostic impact and identify a possible cutoff value of CTC-high for the prediction of progression-free survival (PFS) and overall survival (OS), in the context of concomitant risk features and minimal residual disease (MRD) achievement.

METHODS: CTC were analyzed at diagnosis with two-tube single-platform flow cytometry (sensitivity 4 × 10^-5) in patients enrolled in the multicenter randomized FORTE clinical trial (ClinicalTrials.gov identifier: NCT02203643). MRD was assessed by second-generation multiparameter flow cytometry (sensitivity 10^-5). We tested different cutoff values in series of multivariate (MV) Cox proportional hazards regression analyses on PFS outcome and selected the value that maximized the Harrell’s C-statistic. We analyzed the impact of CTC on PFS and OS in a MV analysis including baseline features and MRD negativity.

RESULTS: CTC analysis was performed in 401 patients; the median follow-up was 50 months (interquartile range, 45-54 months). There was a modest correlation between the percentage of CTC and bone marrow plasma cells (r = 0.38). We identified an optimal CTC cutoff of 0.07% (approximately 5 cells/µL, C-index 0.64). In MV analysis, CTC-high versus CTC-low patients had significantly shorter PFS (hazard ratio, 2.61; 95% CI, 1.49 to 2.97, P < .001; 4-year PFS 38% v 69%) and OS (hazard ratio, 2.61; 95% CI, 1.49 to 4.56; P < .001; 4-year OS 68% v 92%). The CTC levels, but not the bone marrow plasma cell levels, affected the outcome. The only factor that reduced the negative impact of CTC-high was the achievement of MRD negativity (interaction P = .039).

CONCLUSION: In multiple myeloma, increasing levels of CTC above an optimal cutoff represent an easy-to-assess, robust, and independent high-risk factor. The achievement of MRD negativity is the most important factor that modulates their negative prognostic impact.

PMID:35666982 | DOI:10.1200/JCO.21.01393