Category: Statistics

Cell Mol Life Sci. 2021 Mar 13. doi: 10.1007/s00018-021-03808-8. Online ahead of print.

ABSTRACT

The COVID-19 pandemic poses a major burden on healthcare and economic systems across the globe. Even though a majority of the population develops only minor symptoms upon SARS-CoV-2 infection, a significant number are hospitalized at intensive care units (ICU) requiring critical care. While insights into the early stages of the disease are rapidly expanding, the dynamic immunological processes occurring in critically ill patients throughout their recovery at ICU are far less understood. Here, we have analysed whole blood samples serially collected from 40 surviving COVID-19 patients throughout their recovery in ICU using high-dimensional cytometry by time-of-flight (CyTOF) and cytokine multiplexing. Based on the neutrophil-to-lymphocyte ratio (NLR), we defined four sequential immunotypes during recovery that correlated to various clinical parameters, including the level of respiratory support at concomitant sampling times. We identified classical monocytes as the first immune cell type to recover by restoration of HLA-DR-positivity and the reduction of immunosuppressive CD163 + monocytes, followed by the recovery of CD8 + and CD4 + T cell and non-classical monocyte populations. The identified immunotypes also correlated to aberrant cytokine and acute-phase reactant levels. Finally, integrative analysis of cytokines and immune cell profiles showed a shift from an initially dysregulated immune response to a more coordinated immunogenic interplay, highlighting the importance of longitudinal sampling to understand the pathophysiology underlying recovery from severe COVID-19.

PMID:33715015 | DOI:10.1007/s00018-021-03808-8

Aging (Albany NY). 2021 Mar 10;13. doi: 10.18632/aging.202689. Online ahead of print.

ABSTRACT

BACKGROUND: Early diagnosis of severe acute pancreatitis (SAP) is essential to minimize its mortality and improve prognosis. We aimed to develop an accurate and applicable machine learning predictive model based on routine clinical testing results for stratifying acute pancreatitis (AP) severity.

RESULTS: We identified 11 markers predictive of AP severity and trained an AP stratification model called APSAVE, which classified AP cases within 24 hours at an average area under the curve (AUC) of 0.74 +/- 0.04. It was further validated in 568 validation cases, achieving an AUC of 0.73, which is similar to that of Ranson’s criteria (AUC = 0.74) and higher than APACHE II and BISAP (AUC = 0.69 and 0.66, respectively).

CONCLUSIONS: We developed and validated a venous blood marker-based AP severity stratification model with higher accuracy and broader applicability, which holds promises for reducing SAP mortality and improving its clinical outcomes.

MATERIALS AND METHODS: Nine hundred and forty-five AP patients were enrolled into this study. Clinical venous blood tests covering 65 biomarkers were performed on AP patients within 24 hours of admission. An SAP prediction model was built with statistical learning to select biomarkers that are most predictive for AP severity.

PMID:33714951 | DOI:10.18632/aging.202689

Aging (Albany NY). 2021 Mar 10;13. doi: 10.18632/aging.202672. Online ahead of print.

ABSTRACT

In this study, we investigated whether nutrition status mediates the relationship between cognitive decline and sarcopenia. Sarcopenia was assessed in 4023 community-dwelling older adults from West China using the AWGS 2014 diagnostic criteria. Cognitive function and nutrition status were assessed using the 10-item Short Portable Mental Status Questionnaire (SPMSQ) and Mini Nutrition Assessment-Short Form (MNA-SF) scale, respectively. Mediation model regression analysis demonstrated that nutrition status was negatively associated with sarcopenia (β = -0.521; 95% CI: -0.583 to -0.459). The indirect effects of cognitive decline on sarcopenia were significant after adjusting for age, sex, and ethnicity (β = 0.015; 95% CI: 0.012 to 0.017), but the direct effects of cognitive decline on sarcopenia were not statistically significant after adding nutrition status as a parameter in the mediation model analysis (β = -0.001; 95% CI: -0.008 to 0.005). Structural equation model (SEM) framework pathway analysis confirmed the association between nutrition status, cognitive decline, and sarcopenia. These findings demonstrate that the negative effects of cognitive decline on sarcopenia were mediated by nutrition status. We therefore postulate that maintaining a good nutrition status delays the negative effects of cognitive decline on sarcopenia in older adults.

PMID:33714959 | DOI:10.18632/aging.202672

Aging (Albany NY). 2021 Mar 10;13. doi: 10.18632/aging.202686. Online ahead of print.

ABSTRACT

This study aimed to construct and validate an immunoscore nomogram that may be used to predict the prognosis of oesophageal cancer. With the gene expression data of oesophageal cancer in a public database, we used CIBERSORT to estimate the fractions of 22 infiltrating immune cell types. We then built an immunoscore signature based on 12 types of infiltrating immune cells using the least absolute shrinkage and selection operator (LASSO) model. This immunoscore was used as an independent predictor in the prognostic model (training cohort: [hazard ratio (HR), 4.78; 95% confidence interval (CI), 2.64-8.67; P < 0.001], validation cohort: [HR, 2.15; 95% CI, 1.04-4.45; P = 0.040]). Subgroup analysis by clinical features showed that overall survival was significantly different between the high-immunoscore group and the low-immunoscore group. The predictors that constituted the individualized prediction nomogram were immunoscore, age, and tumour stage. The nomogram had good discrimination and calibration. Decision curve analysis showed that the immunoscore nomogram was clinically useful. Therefore, the novel immunoscore signature based on infiltrating immune cells can be used as a reliable predictor of the prognosis of oesophageal cancer, and the immunoscore nomogram is a convenient tool for predicting the survival of individual patients.

PMID:33714960 | DOI:10.18632/aging.202686

Acta Paediatr. 2021 Mar 13. doi: 10.1111/apa.15842. Online ahead of print.

ABSTRACT

AIM: This study explored the differences in demographic and socioeconomic factors between children hospitalised due to four common viral infections.

METHODS: Demographic data were obtained from Statistics Sweden on >3,000 children admitted to Astrid Lindgren Children’s Hospital in 2009-2014 with rotavirus, influenza, respiratory syncytial virus (RSV), or chickenpox. We compared demographic and socioeconomic factors between case groups using logistic regression with rotavirus cases as reference.

RESULTS: There were differences in the median age at admission; RSV cases were younger (0.4 years), influenza (2.4 years) and chickenpox cases (2.7 years) older than rotavirus cases (1.2 years). RSV, influenza and chickenpox cases lived in families with more children than rotavirus cases. RSV and influenza cases were more likely to have underlying chronic conditions. Mothers of RSV cases were more likely to be born in Sweden. Further socioeconomic differences were not robustly confirmed in sensitivity analyses.

CONCLUSION: We found a few differences in demographic factors between children hospitalised with the four common infections, which were mainly explained by the epidemiology and transmission patterns of these infections.

PMID:33714232 | DOI:10.1111/apa.15842

Colorectal Dis. 2021 Mar 13. doi: 10.1111/codi.15625. Online ahead of print.

ABSTRACT

AIM: Covid-19 has delayed elective colorectal cancer (CRC) surgery. The aim of this study was to see whether or not this may affect overall survival (OS) and disease-free survival (DFS).

METHODS: A systematic review was carried out in according to PRISMA guidelines (PROSPERO ID: CRD42020189158). Medline, EMBASE and Scopus were interrogated. Patients aged over 18 with a diagnosis of colon or rectal cancer who received elective surgery as their primary treatment were included. Delay to elective surgery was defined as the period between CRC diagnosis and the day of surgery. Meta-analysis of the outcomes OS and DFS were conducted. Forest plots, funnel plots, and tests of heterogeneity were produced. An estimated Number Needed to Harm (NNH) was calculated for statistically significant pooled Hazard Ratios (HRs).

RESULTS: Of 3753 articles identified, seven met the inclusion criteria. Encompassing 314560 patients, three of the seven studies showed that a delay to elective resection is associated with poorer OS or DFS. OS was assessed at a one-month delay, the HR for six datasets was 1.13 (95%CI 1.02-1.26, p = 0.020) and at three months the pooled HR for three datasets was 1.57 (95%CI 1.16-2.12, p = 0.004). Estimated NNH for a delay at one month and three months were 35 and 10 respectively. Delay was non-significantly negatively associated with DFS on metanalysis.

CONCLUSION: This study suggests that postponing elective CRC surgery by more than four weeks, after diagnosis is associated with a poorer outcome. Future research should try and identify those patients most at risk so that they can be prioritized in the event of any future pandemic.

PMID:33714235 | DOI:10.1111/codi.15625

Aging (Albany NY). 2021 Mar 10;13. doi: 10.18632/aging.202654. Online ahead of print.

ABSTRACT

We previously showed that donor plasma mitochondrial DNA (dmtDNA) levels were correlated with renal allograft function. The aim of the current study was to determine whether dmtDNA levels are associated with the occurrence of antibody-mediated rejection (ABMR). This is a retrospective open cohort study comprised of 167 donors and 323 recipients enrolled from January 2015 to December 2017. We quantified the mtDNA level present in donor plasma using quantitative real-time polymerase chain reaction. The average plasma dmtDNA level in the acute rejection (AR) group was higher than that of the control group (0.156 versus 0.075, p<0.001). Multivariate logistic regression analysis showed that dmtDNA levels were also significantly associated with AR (OR=1.588, 95% CI 1.337-4.561, p<0.001). When the dmtDNA level was >0.156, the probability of AR was 62.9%. The plasma dmtDNA level in the ABMR group was significantly higher than that of the T cell-mediated rejection group (0.185 versus 0.099, p=0.032). The area under the receiver operating characteristic curve of dmtDNA for prediction of ABMR was as high as 0.910 (95% CI 0.843-0.977). We demonstrated that plasma dmtDNA was an independent risk factor for ABMR, which is valuable in organ evaluation. dmtDNA level is a possible first predictive marker for ABMR.

PMID:33714205 | DOI:10.18632/aging.202654

Mol Ecol. 2021 Mar 13. doi: 10.1111/mec.15882. Online ahead of print.

ABSTRACT

Disentangling the biogeographic patterns of rare and abundant microbes is essential in order to understand the generation and maintenance of microbial diversity with respect to the functions they provide. However, little is known about ecological assembly processes and environmental adaptation of rare and abundant microbes across large spatial-scale wetlands. Using Illumina sequencing and multiple statistical analyses, we characterized the taxonomic and phylogenetic diversity of rare and abundant bacteria and fungi in Qinghai-Tibet Plateau wetland soils. Abundant microbial taxa exhibited broader environmental thresholds and stronger phylogenetic signals for ecological traits than rare ones. By contrast, rare taxa showed higher sensitivity to environmental changes and closer phylogenetic clustering than abundant ones. The null model analysis revealed that dispersal limitation belonging to stochastic process dominated community assemblies of abundant bacteria, and rare and abundant fungi, while variable selection belonging to deterministic process governed community assembly of rare bacteria. Neutral model analysis and variation partitioning analysis further confirmed that abundant microbes were less environmentally constrained. Soil ammonia nitrogen was the crucial factor in mediating the balance between stochasticity and determinism of both rare and abundant microbes. Abundant microbes may have better environmental adaptation potential and are less dispersed by environmental changes than rare ones. Our findings extend knowledge of the adaptation of rare and abundant microbes to ongoing environmental change and could facilitate prediction of biodiversity loss caused probably by climate change and human activity in the Qinghai-Tibet Plateau wetlands.

PMID:33714213 | DOI:10.1111/mec.15882

Int J Urol. 2021 Mar 13. doi: 10.1111/iju.14537. Online ahead of print.

ABSTRACT

OBJECTIVES: To compare perioperative and oncologic survival outcomes between laparoscopic radical cystectomy and open radical cystectomy.

METHODS: A total of 607 patients underwent open radical cystectomy (n = 412) or laparoscopic radical cystectomy (n = 195) at a single academic institution from January 2006 to April 2017. Their medical records were retrospectively analyzed. One-to-one propensity score matching was carried out to reduce selection bias. Estimated blood loss and complications were compared. Overall survival, cancer-specific survival and progression-free survival estimates for all patients and patients with locally advanced bladder cancer were analyzed using the Kaplan-Meier method.

RESULTS: Either before or after matching, the laparoscopic radical cystectomy group had less estimated blood loss (P < 0.001 and P < 0.001) and fewer complications (P < 0.001 and P = 0.008). There was no difference in the overall survival (P = 0.216 and P = 0.961) and progression-free survival (P = 0.826 and P = 0.462) for all the patients having either laparoscopic radical cystectomy or open radical cystectomy. However, the 5-year progression-free survival of open radical cystectomy was higher than that of laparoscopic radical cystectomy (P = 0.019 and P = 0.021) for patients with locally advanced bladder cancer.

CONCLUSIONS: Laparoscopic radical cystectomy is superior to open radical cystectomy in terms of perioperative outcomes, and similar to open radical cystectomy in terms of oncologic outcomes for patients with early stage bladder cancer. However, for patients with locally advanced bladder cancer, laparoscopic radical cystectomy seems to be associated with shorter progression-free survival than open radical cystectomy.

PMID:33714227 | DOI:10.1111/iju.14537

Chemosphere. 2021 Feb 26;276:130118. doi: 10.1016/j.chemosphere.2021.130118. Online ahead of print.

ABSTRACT

The objective of this study was to evaluate the effects of gestational exposure to low doses of bisphenol A (BPA), bisphenol S (BPS), and bisphenol F (BPF) on pregnancy outcomes and offspring development. Pregnant Sprague-Dawley rats were orally dosed with vehicle, 5 μg/kg body weight (BW)/day of BPA, BPS and BPF, or 1 μg/kg BW/day of BPF on gestational days 6-21. Pregnancy and gestational outcomes, including number of abortions and stillbirths, were monitored. Male and female offspring were subjected to morphometry at birth, followed by pre- and post-weaning body weights, post-weaning food and water intakes, and adult organ weights. Ovarian follicular counts were also obtained from adult female offspring. We observed spontaneous abortions in over 80% of dams exposed to 5 μg/kg of BPF. BPA exposure increased Graafian follicles in female offspring, while BPS and BPF exposure decreased the number of corpora lutea, suggesting reduced ovulation rates. Moreover, BPA exposure increased male kidney and prostate gland weights, BPF decreased epididymal adipose tissue weights, and BPS had modest effects on male abdominal adipose tissue weights. Prenatal BPS exposure reduced anogenital distance (AGD) in male offspring, suggesting possible feminization, whereas both BPS and BPA induced oxidative stress in the testes. These results indicate that prenatal exposure to BPF affects pregnancy outcomes, BPS alters male AGD, and all three bisphenols alter certain organ weights in male offspring and ovarian function in female offspring. Altogether, it appears that prenatal exposure to BPA or its analogues can induce reproductive toxicity even at low doses.

PMID:33714148 | DOI:10.1016/j.chemosphere.2021.130118