Tag: statistics

Eur Heart J. 2021 Feb 27:ehab110. doi: 10.1093/eurheartj/ehab110. Online ahead of print.

ABSTRACT

BACKGROUND : Cardiogenic shock (CS) complicating acute myocardial infarction (AMI) still reaches excessively high mortality rates. This analysis is aimed to develop a new easily applicable biomarker-based risk score.

METHODS AND RESULTS : A biomarker-based risk score for 30-day mortality was developed from 458 patients with CS complicating AMI included in the randomized CULPRIT-SHOCK trial. The selection of relevant predictors and the coefficient estimation for the prognostic model were performed by a penalized multivariate logistic regression analysis. Validation was performed internally, internally externally as well as externally in 163 patients with CS included in the randomized IABP-SHOCK II trial. Blood samples were obtained at randomization. The two trials are registered with ClinicalTrials.gov (NCT01927549 and NCT00491036), are closed to new participants, and follow-up is completed. Out of 58 candidate variables, the four strongest predictors for 30-day mortality were included in the CLIP score (cystatin C, lactate, interleukin-6, and N-terminal pro-B-type natriuretic peptide). The score was well calibrated and yielded high c-statistics of 0.82 [95% confidence interval (CI) 0.78-0.86] in internal validation, 0.82 (95% CI 0.75-0.89) in internal-external (temporal) validation, and 0.73 (95% CI 0.65-0.81) in external validation. Notably, it outperformed the Simplified Acute Physiology Score II and IABP-SHOCK II risk score in prognostication (0.83 vs 0.62; P < 0.001 and 0.83 vs. 0.76; P = 0.03, respectively).

CONCLUSIONS : A biomarker-only score for 30-day mortality risk stratification in infarct-related CS was developed, extensively validated and calibrated in a prospective cohort of contemporary patients with CS after AMI. The CLIP score outperformed other clinical scores and may be useful as an early decision tool in CS.

PMID:33647946 | DOI:10.1093/eurheartj/ehab110

Bioinformatics. 2021 Feb 27:btab136. doi: 10.1093/bioinformatics/btab136. Online ahead of print.

ABSTRACT

MOTIVATION: Many recent advancements in single molecule localisation microscopy exploit the stochastic photo-switching of fluorophores to reveal complex cellular structures beyond the classical diffraction limit. However, this same stochasticity makes counting the number of molecules to high precision extremely challenging, preventing key insight into the cellular structures and processes under observation.

RESULTS: Modelling the photo-switching behaviour of a fluorophore as an unobserved continuous time Markov process transitioning between a single fluorescent and multiple dark states, and fully mitigating for missed blinks and false positives, we present a method for computing the exact probability distribution for the number of observed localisations from a single photo-switching fluorophore. This is then extended to provide the probability distribution for the number of localisations in a dSTORM experiment involving an arbitrary number of molecules. We demonstrate that when training data is available to estimate photoswitching rates, the unknown number of molecules can be accurately recovered from the posterior mode of the number of molecules given the number of localisations. Finally, we demonstrate the method on experimental data by quantifying the number of adapter protein Linker for Activation of T cells (LAT) on the cell surface of the T cell immunological synapse.

AVAILABILITY: Software available at https://github.com/lp1611/mol_count_dstorm.

SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

PMID:33647949 | DOI:10.1093/bioinformatics/btab136

Cancer Treat Res Commun. 2021 Feb 24;27:100343. doi: 10.1016/j.ctarc.2021.100343. Online ahead of print.

ABSTRACT

BACKGROUND: No large-scale study evaluating the usefulness of tamoxifen after meningioma surgery has been undertaken.

METHODS: We processed the French Système National des Données de Santé (SNDS) database using an algorithm combining the type of surgical procedure and the International Classification of Diseases to retrieve cases of meningiomas operated between 2007 and 2017. Survival analyses were performed using a matched cohort study.

RESULTS: 251 patients treated by tamoxifen were extracted from a nationwide population-based cohort of 28 924 patients operated on for a meningioma over a 10-year period. 94% were female and median age at meningioma first surgery was 57 years IQR[47-67]. Tamoxifen treatment median duration was 1.4 years IQR[0.4-3.2]. Tamoxifen treatment median cumulative given dose was 11.4 gs, IQR[3.6-24.9]. There was a strong positive correlation between treatment duration and cumulative dose (τ=0.81, p<0.001). 6% of the patient had to be reoperated for a meningioma recurrence and 26.3% had radiotherapy. OS rates at 5 and 10 years were: 92.3%, _95%CI[90.3-94.3] and 81.3%, _95%CI[75.2-88] respectively. These 251 patients were matched by gender, age at surgery and grade with the same number of subjects within the nationwide cohort. Nor overall (HR=1.46, _95%CI[0.86- 2.49], p=0.163) or progression-free survival (HR=1.2, _95%CI[0.89- 1.62], p=0.239) were significantly improved by the tamoxifen treatment.

CONCLUSION: Using this unique database, in the setting of breast cancer, we could not conclude on a favourable effect of tamoxifen to prevent recurrence after meningioma surgery or to increase meningioma-related survival even in case of prolonged treatment duration or high cumulative given dose.

PMID:33647870 | DOI:10.1016/j.ctarc.2021.100343

Urol Int. 2021 Mar 1:1-8. doi: 10.1159/000505757. Online ahead of print.

ABSTRACT

OBJECTIVES: The aim of the study was to assess the efficacy and safety of an enhanced recovery program (ERP) after robot-assisted partial nephrectomy (RAPN) for cancer.

METHODS: It was a monocentric, retrospective, comparative study. An ERP after RAPN was introduced at our institution in 2015 and proposed to all consecutive patients admitted for RAPN. The control group for this study was composed of patients managed immediately before the introduction of the ERP. We collected information on patient characteristics, tumor sizes, ischemia times, biology, hospital length of stays, postoperative (≤30 days) complications, and readmission rates. Group comparisons were made using the Pearson χ2 test for qualitative data and the Student t test for quantitative data.

RESULTS: Between 2015 and 2017, 112 patients were included in the ERP group. Fifty patients were included in the control group. Ninety patients in the ERP group (80.4%) were discharged at or before postoperative day (POD) 2 versus 10 patients (20%) in the control group (p < 0.001). There was no significant difference between the ERP and control groups for the urinary retention rate (respectively 3.6 vs. 2%; p = 0.593). Resumption of normal bowel function was significantly shorter in the ERP group (94.6% at POD1 vs. 69.6% in the control group, p < 0.001). There were no significant differences for postoperative complications (15.2% in the ERP group vs. 20% in the control group, p = 0.447) or readmissions within 30 days (8.04 vs. 0.2%, p = 0.140).

CONCLUSIONS: ERP after RAPN seems to reduce postoperative length of stay without increasing postoperative complications or readmissions.

PMID:33647899 | DOI:10.1159/000505757

Dermatology. 2021 Mar 1:1-7. doi: 10.1159/000512931. Online ahead of print.

ABSTRACT

BACKGROUND: Ulcerative colitis (UC) is a well-known underlying comorbidity of pyoderma gangrenosum (PG). However, the risk conferred by UC for the subsequent development of PG is yet to be elucidated. We aimed to estimate the magnitude of the association between UC and the subsequent occurrence of PG, which would enable us to assess the odds of PG developing in individuals with a history of UC.

METHODS: A population-based case-control study was conducted to compare PG patients (n = 302) and age-, sex- and ethnicity-matched control subjects (n = 1,497) regarding the presence of UC. Logistic regression models were utilized for univariate and multivariate analyses.

RESULTS: The prevalence of preexisting UC was greater in patients with PG than in controls (7.3 vs. 0.5%; p < 0.001). A 15-fold increase in the odds of PG in individuals with preexisting UC was observed (OR 14.62, 95% CI 6.45-33.18). The greatest risk of developing PG occurred in the first years following the diagnosis of UC (OR 35.50, 95% CI 4.35-289.60), and decreased thereafter to 10.03 (95% CI 1.83-55.03), 6.69 (95% CI 1.49-30.02), and 10.03 (95% CI 1.83-55.03) at 1-5, 5-10, and 10-15 years after the diagnosis of UC, respectively. This association retained its statistical significance following the adjustment for confounding factors (adjusted OR 10.78, 95% CI 4.55-25.52). Patients with both PG and UC were younger and had a lower prevalence of smoking than the remaining patients with PG.

CONCLUSIONS: UC increases the odds of developing PG by 15-fold, with the highest probability of developing PG occurring within the first year after the diagnosis of UC. Patients with UC may be advised to avoid additional precipitating factors for the development of PG.

PMID:33647909 | DOI:10.1159/000512931

Bioinformatics. 2021 Feb 27:btab139. doi: 10.1093/bioinformatics/btab139. Online ahead of print.

ABSTRACT

MOTIVATION: Trans-acting expression quantitative trait loci (eQTLs) collectively explain a substantial proportion of expression variation, yet are challenging to detect and replicate since their effects are often individually weak. A large proportion of genetic effects on distal genes are mediated through cisgene expression. Cis-association (between SNP and cis-gene) and gene-gene correlation conditional on SNP genotype could establish trans-association (between SNP and trans-gene). Both cis-association and gene-gene conditional correlation have effects shared across relevant tissues and conditions, and transassociations mediated by cis-gene expression also have effects shared across relevant conditions.

RESULTS: . We proposed a Cross-Condition Mediation analysis method (CCmed) for detecting cis-mediated trans-associations with replicable effects in relevant conditions/studies. CCmed integrates cis-association and gene-gene conditional correlation statistics from multiple tissues/studies. Motivated by the bimodal effect-sharing patterns of eQTLs, we proposed two variations of CCmed, CCmedmost and CCmedspec for detecting cross-tissue and tissue-specific trans-associations, respectively. We analyzed data of 13 brain tissues from the Genotype-Tissue Expression (GTEx) project, and identified trios with cis-mediated transassociations across brain tissues, many of which showed evidence of trans-association in two replication studies. We also identified trans-genes associated with schizophrenia loci in at least two brain tissues.

AVAILABILITY AND IMPLEMENTATION: CCmed software is available at http://github.com/kjgleason/CCmed.

SUPPLEMENTARY INFORMATION: Supplementary Material are available at Bioinformatics online.

PMID:33647928 | DOI:10.1093/bioinformatics/btab139

Pregnancy Hypertens. 2021 Feb 13;24:37-43. doi: 10.1016/j.preghy.2021.02.003. Online ahead of print.

ABSTRACT

PURPOSE: An elevated soluble fms-like tyrosine kinase-1 (sFlt-1) / placental growth factor (PlGF) ratio is associated with adverse perinatal outcome (APO) and the mean time until delivery (MTUD) in singleton pregnancies complicated by pre-eclampsia (PE). Data on APO and MTUD prediction in twin pregnancies using sFlt-1/PlGF ratio are scarce. We evaluated the predictive value of the sFlt-1/PIGF ratio regarding APO and MTUD in twin pregnancies with suspected PE and/or HELLP syndrome.

METHODS: This is a single center retrospective cohort study. All twin pregnancies with suspected PE/HELLP and determined sFlt-1/PIGF were included. Composite APO (CAPO) was defined as the presence of at least one of the following outcomes: respiratory distress syndrome (RDS), intubation, admission to neonatal intensive care unit (NICU) and arterial umbilical cord pH value < 7.10. Selective fetal growth restriction (s-FGR) was analyzed separately.

RESULTS: For final analysis, 49 twin pregnancies were included. Median sFlt-1/PIGF ratio was not significantly different in patients with CAPO compared to those without (89.45 vs. 62.00, p = 0.669). MTUD was significantly negative correlated with sFlt-1/PIGF ratio (r = -0.409, p < 0.001). For the whole study cohort, ROC analysis revealed no predictive value for sFlt-1/PIGF and CAPO (AUC = 0.618, 95% CI: 0.387-0.849, p = 0.254). However, sFlt-1/PIGF ratio showed a predictive value for s-FGR (AUC = 0.755, 95% CI: 0.545-0.965, p = 0.032).

CONCLUSION: In twin pregnancies with PE and/or HELLP, sFlt-1/PIGF ratio may be helpful for s-FGR prediction and decision-making regarding close monitoring of high-risk patients. However, further prospective studies are warranted to define the role of sFlt-1/PlGF ratio as outcome predictor in twin pregnancies.

PMID:33647841 | DOI:10.1016/j.preghy.2021.02.003

Int J Paleopathol. 2021 Feb 26;33:30-42. doi: 10.1016/j.ijpp.2020.12.002. Online ahead of print.

ABSTRACT

OBJECTIVE: A malformed pectoral joint of the middle Devonian antiarch fish Asterolepis ornata is described, and a survey of congenital malformations in the fossil record is provided.

MATERIALS: The specimen of A. ornata (MB.f.73) from Ehrman in Latvia, stored at the Museum für Naturkunde Berlin, Germany.

METHODS: A. ornata was macroscopically and radiologically investigated, and the overview on congenital malformation was based on an extensive literature survey.

RESULTS: In the deformed joint of A. ornata, the articular surfaces and muscle attachment sites are greatly reduced, indicating restricted mobility. Congenital malformations can be found since the middle Silurian and affect all groups of vertebrates, but they are rare. Teeth and the vertebral column are the most commonly affected anatomical regions, and the mechanisms causing these malformations probably remained the same through geological time.

CONCLUSIONS: Micro-CT of the deformed joint shows no disturbance of the normal trabecular pattern and no evidence of trauma or disease, suggesting a congenital hypoplasia, although an acquired deformity cannot be ruled out completely.

SIGNIFICANCE: Congenital malformations, even those that are rare, were part of the common history of vertebrates for more than 400 million years.

LIMITATIONS: Epidemiologic measures like incidence and prevalence usually cannot be applied to define rare diseases in the fossil record.

SUGGESTIONS FOR FURTHER RESEARCH: A broadly based analysis of species of fossil vertebrates with numerus recovered specimens (e.g. many bony fishes, amphibians, certain dinosaurs) might statistically affirm the occurrence of malformations and possible correlations with the paleoenvironment.

PMID:33647859 | DOI:10.1016/j.ijpp.2020.12.002

Pathol Res Pract. 2021 Feb 17;220:153386. doi: 10.1016/j.prp.2021.153386. Online ahead of print.

ABSTRACT

Warthin tumour (WT) is a benign tumour of the salivary gland that proliferates in both glandular epithelial and lymphoid tissue components, and rarely exhibits cystic changes. T follicular helper cells (Tfh) are involved in the formation and maintenance of germinal centres, the differentiation of B cells into plasma cells, and the maintenance of helper T cell type 2 (Th2)-dominant humoral immune responses. T-bet induces differentiation into helper T cell type 1 (Th1) by suppressing differentiation into Tfh and enhances cellular immune responses. The objective of this study was to enhance our understanding of the immune responses and relationship between Tfh and Th1 cells in patients with WTs. In this study, we classified WTs (n = 64) into solid-type (n = 25) and cyst-type (n = 39). We also performed immunostaining of the Tfh markers CXCR5 and CD40 L, and the Th1 marker T-bet for statistical analysis. The cyst-type exhibited significant atrophy of the germinal centre area (P = 0.0019), significantly fewer Tfh-positive lymphocytes in germinal centres (P < 0.0001), and significantly more T-bet-positive lymphocytes in the epithelium (P = 0.0017). We observed that Tfh were involved in the formation and maintenance of lymphoid follicles in WTs. In the cyst-type, Th2-dominant humoral immune responses were suppressed, and Th1-dominant cellular immune responses may have caused damage to tumour tissue.

PMID:33647861 | DOI:10.1016/j.prp.2021.153386

J Clin Virol. 2021 Feb 20;137:104779. doi: 10.1016/j.jcv.2021.104779. Online ahead of print.

ABSTRACT

PURPOSE: Genotypic resistance-related mutations in HIV-1 disease are often difficult to interpret. Different algorithms have been developed to provide meaningful application into clinical context. We aimed to compare, for the first time in Greece, the results of genotypic resistance derived from three interpretation algorithms.

METHODS: The sequences of 120 HIV 1-infected patients were tested for genotypic resistance to 19 antiretroviral (ARV) drugs (n = 2280 sequences). The interpretation results of Rega, ANRS and ViroSeq algorithms were compared.

RESULTS: Complete concordance was found for 2/19 ARV drugs, namely lamivudine and emptricitabine. Concordance was high for nucleoside reverse transcriptase inhibitors (NRTIs) and low for protease inhibitors (PIs). In inter-algorithm pairs, agreement was high between Rega and ViroSeq (kappa = 0.701), especially by ARV class, namely NRTIs (k = 0.869) and NNRTIs (k = 0.562). The only exception was noted for rilpivirine, where agreement was higher between ANRS and Rega (k = 0.410) compared to other inter-algorithm pairs (k = 0.018-0.055). By contrast, for PIs all comparisons yielded concordance equivalent to chance (k = 0.000).

CONCLUSIONS: Our exploratory analysis provided evidence of significant inter-algorithm discordances, especially for PIs and NNRTIs highlighting the importance of matching the results of different algorithms to achieve optimized risk stratification. Ongoing research could assist clinical physicians in interpreting complex genotypic resistance patterns.

PMID:33647801 | DOI:10.1016/j.jcv.2021.104779