Category: Statistics

Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2023 May 10;40(5):532-537. doi: 10.3760/cma.j.cn511374-20201015-00721.

ABSTRACT

OBJECTIVE: To assess the value of chromosomal microarray analysis (CMA) and trio-whole exome sequencing (trio-WES) for fetuses with increased nuchal translucency (NT) thickness.

METHODS: Sixty two pregnant women who had visited Urumqi Maternal and Child Care Health Hospital between June 2018 and June 2020 for NT ≥ 3.0 mm at 11 ~ 13⁺⁶ gestational weeks were selected as study subjects. Relevant clinical data were collected. The patients were divided into 3.0 ~ ＜3.5 mm (n = 33) and ≥3.5 mm groups (n = 29). Chromosome karyotyping analysis and chromosomal microarray analysis were carried out. And trio-WES analysis was performed on 15 samples with NT thickening but negative CMA results. The distribution and incidence of chromosomal abnormalities in the two groups were compared by using chi-square test.

RESULTS: The median age of the pregnant women was 29 years old (22 ~ 41 years old), the median thickness of NT was 3.4 mm (3.0 ~ 9.1 mm), and the median gestational age at the detection was 13⁺⁴ weeks (11⁺⁵ ~ 13⁺⁶ weeks). Chromosome karyotyping analysis has detected 12 cases of aneuploidies and 1 case of derivative chromosome. The detection rate was 20.97% (13/62). CMA has detected 12 cases of aneuploidies, 1 case of pathogenic CNV and 5 cases of variant of uncertain significance (VUS), with a detection rate of 29.03% (18/62). The aneuploidy rate for the NT ≥ 3.5 mm group was higher than that for the 3.0 ≤ NT < 3.5 mm group [3.03% (1/33) vs. 41.38% (12/29), χ² = 13.698, P < 0.001]. There was no statistically significant difference between the two groups in the detection rate of fetal pathogenic CNV and VUS (χ² = 0.028, P > 0.05). Trio-WES analysis of 15 samples with negative CMA result and no structural abnormality has identified 6 heterozygous variants, including SOS1: c.3542C>T (p.A1181V) and c.3817C>G (p.L1273V), COL2A1: c.436C>T (p.P146S) and c.3700G>A (p.D1234N), LZTR1: c.1496T>C (p.V499A), and BRAF: c.64G>A (p.D22N), respectively. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), all of the variants were rated as VUS.

CONCLUSION: NT thickening can indicate chromosome abnormality, and CMA and trio-WES may be used for the prenatal diagnosis.

PMID:37102284 | DOI:10.3760/cma.j.cn511374-20201015-00721

Neuroradiol J. 2023 Apr 27:19714009231173109. doi: 10.1177/19714009231173109. Online ahead of print.

ABSTRACT

OBJECTIVES: Idiopathic intracranial hypertension (IIH) is a disease defined by elevated intracranial pressure (ICP) without an established etiology. Arachnoid granulations (AG) are conduits for CSF resorption from the subarachnoid space to the venous system. AG have been implicated to play a central role in maintaining CSF homeostasis. We tested the hypothesis that patients with fewer visible AG on MRI are more likely to present with IIH.

METHODS: In this institutional review board (Institutional Review Board)-approved retrospective chart review study, 65 patients with a clinical diagnosis of idiopathic intracranial hypertension were compared to 144 control patients who met inclusion/exclusion criteria. Patients’ signs and symptoms pertaining to IIH were obtained through the electronic medical record Brain MR images were reviewed for the number and distribution of AGs indenting the dural venous sinuses. The presence of imaging and clinical findings associated with long standing increased ICP was noted. Propensity score method (with inverse probability weighting technique) was used to compare case and control groups.

RESULTS: In the control group, the number of AG indenting the dural venous sinuses on MRI (NAG) was lower in women compared to men when matched for age (20-45 yo) and BMI (>30 kg/m²). The NAG was lower in 20-45 yo females in the IIH group as compared to the 20-45 yo females in the control group. This statistically significant difference persists when controlled for BMI. In contrast, the NAG in >45 yo females in the IIH group trended higher compared to the >45 yo females in the control group.

CONCLUSION: Our results suggest that alterations in arachnoid granulations could play a role in the development of IIH.

PMID:37102274 | DOI:10.1177/19714009231173109

Med Phys. 2023 Apr 27. doi: 10.1002/mp.16430. Online ahead of print.

ABSTRACT

BACKGROUND: Cancer prognosis before and after treatment is key for patient management and decision making. Handcrafted imaging biomarkers-radiomics-have shown potential in predicting prognosis.

PURPOSE: However, given the recent progress in deep learning, it is timely and relevant to pose the question: could deep learning based 3D imaging features be used as imaging biomarkers and outperform radiomics?

METHODS: Effectiveness, reproducibility in test/retest, across modalities, and correlation of deep features with clinical features such as tumor volume and TNM staging were tested in this study. Radiomics was introduced as the reference image biomarker. For deep feature extraction, we transformed the CT scans into videos, and we adopted the pre-trained Inflated 3D ConvNet (I3D) video classification network as the architecture. We used four datasets-LUNG 1 (n = 422), LUNG 4 (n = 106), OPC (n = 605), and H&N 1 (n = 89)-with 1270 samples from different centers and cancer types-lung and head and neck cancer-to test deep features’ predictiveness and two additional datasets to assess the reproducibility of deep features.

RESULTS: Support Vector Machine-Recursive Feature Elimination (SVM-RFE) selected top 100 deep features achieved a concordance index (CI) of 0.67 in survival prediction in LUNG 1, 0.87 in LUNG 4, 0.76 in OPC, and 0.87 in H&N 1, while SVM-RFE selected top 100 radiomics achieved CIs of 0.64, 0.77, 0.73, and 0.74, respectively, all statistically significant differences (p < 0.01, Wilcoxon’s test). Most selected deep features are not correlated with tumor volume and TNM staging. However, full radiomics features show higher reproducibility than full deep features in a test/retest setting (0.89 vs. 0.62, concordance correlation coefficient).

CONCLUSION: The results show that deep features can outperform radiomics while providing different views for tumor prognosis compared to tumor volume and TNM staging. However, deep features suffer from lower reproducibility than radiomic features and lack the interpretability of the latter.

PMID:37102270 | DOI:10.1002/mp.16430

Cancer Med. 2023 Apr 27. doi: 10.1002/cam4.6004. Online ahead of print.

ABSTRACT

BACKGROUND: Insulin resistance has been shown to be related to a higher risk of several cancers, but the association with prostate cancer (PCa) has been inconsistent.

METHODS: We investigated prediagnostic markers of insulin resistance in men in four cohorts in Sweden, in relation to PCa risk (total, non-aggressive and aggressive) and PCa death using multivariable-adjusted Cox regression. The number of men, PCa cases and PCa deaths was up to 66,668, 3940 and 473 for plasma glucose and the triglyceride-glucose (TyG) index, and up to 3898, 586 and 102 for plasma insulin, glycated haemoglobin (HbA1c) and leptin.

RESULTS: Higher HbA1c was related to a lower risk of non-aggressive PCa but no significant associations were found for insulin resistance markers with the risk of aggressive or total PCa. In PCa cases, higher glucose and TyG index were related to a higher risk of PCa death (hazard ratio [HR] per higher standard deviation, 1.22, 95% CI 1.00-1.49 and 1.24, 95% CI 1.00-1.55), which further increased when restricting the analyses to glucose and TyG index measures taken <10 years before the PCa diagnosis (HR, 1.70, 95% CI 1.09-2.70 and 1.66, 95% CI 1.12-2.51). No associations were observed for other markers in relation to PCa death.

CONCLUSIONS: The results of this study showed no associations of insulin resistance markers with the risk of clinically relevant PCa, but higher glucose and TyG index were associated with poorer survival from PCa. The lack of association for other insulin resistance markers may be due to their smaller sample size.

PMID:37102250 | DOI:10.1002/cam4.6004

J Anim Breed Genet. 2023 Apr 26. doi: 10.1111/jbg.12776. Online ahead of print.

ABSTRACT

The objective of the present study was to evaluate the breeding value and accuracy of genomic estimated breeding values (GEBVs) of carcass traits in Jeju Black cattle (JBC) using Hanwoo steers and JBC as a reference population using the single-trait animal model. Our research included genotype and phenotype information on 19,154 Hanwoo steers with 1097 JBC acting as the reference population. Likewise, the test population consisted of 418 genotyped JBC individuals with no phenotypic records for those carcass traits. For estimating the accuracy of GEBV, we divided the entire population into three groups. Hanwoo and JBC make up the first group; Hanwoo and JBC, who has both the genotype and phenotypic records, are referred to as the reference (training) population, and JBC, who lacks phenotypic information is referred to as the test (validation) population. The second group consists of the JBC (without phenotype) as the test population and Hanwoo as a reference population with phenotype and genotypic data. The only JBCs in the third group are those who have genotypic and phenotypic data on them as a reference population but no phenotypic data on them as a test population. The single-trait animal model was used in all three groups for statistical purposes. The reference populations estimated heritabilities for carcass weight (CWT), eye muscle area (EMA), backfat thickness (BF), and marbling score (MS) as 0.30, 0.26, 0.26, and 0.34 for the Hanwoo steer and 0.42, 0.27, 0.26, and 0.48 for JBC. The average accuracy for carcass traits in Group 1 was 0.80 for the Hanwoo and JBC reference population compared with 0.73 for the JBC test population. Although the average accuracy for carcass traits in Group 2 was 0.80, it was 0.80 for the Hanwoo reference population and only 0.56 for the JBC test population. The average accuracy for the JBC reference and test populations was 0.68 and 0.50, respectively, when they were included in the accuracy comparison without the Hanwoo reference population. Groups 1 and 2 used Hanwoo as reference population, which led to a better average accuracy; however, Group 3 only used the JBC reference and test population, which led to a lower average accuracy. This might be due to the fact that Group 3 used a smaller reference size than the group that came before it and that the genetic makeup of the Hanwoo and JBC breeds differed. The GEBV accuracy for MS was higher than that of other traits across all three analysis groups, followed by CWT, EMA, and BF, which may be partially explained by the MS traits’ higher heritability. This study suggests that in order to achieve more accuracy, a large reference population particular to a breed should be established. Therefore, to increase the accuracy of GEBV prediction and the genetic benefit from genomic selection in JBC, individual reference breeds, and large populations are required.

PMID:37102238 | DOI:10.1111/jbg.12776

Coron Artery Dis. 2023 Apr 25. doi: 10.1097/MCA.0000000000001246. Online ahead of print.

ABSTRACT

BACKGROUND: Ventricular arrhythmia is a common complication of acute myocardial infarction (AMI). The Arg389Gly polymorphism of the β1-adrenergic receptor genotype may affect AMI patients.

METHOD: Patients diagnosed with AMI were included in this study. Clinical data were obtained from the patient’s medical history, and genotypes were retrieved from laboratory test reports. ECG data were recorded daily. Data analysis was performed using SPSS 20.0, and differences were deemed statistically significant at P < 0.05.

RESULT: In the final study, 213 patients were included. The proportions of the Arg389Arg, Arg389Gly, and Gly389Gly genotypes were 65.7%, 21.6%, and 12.7%, respectively. Patients with the Arg389Arg genotype exhibited significantly elevated cardiac troponin T (cTnT) and pro-BNP levels compared to the Arg389Gly and Gly389Gly genotypes [cTnT: 4.00 ± 2.43 ng/ml versus 2.82 ± 1.82 ng/ml, P = 0.012; pro-BNP: 1942.37 (1223.194, 206.59) pg/ml versus 1604.57 (798.05, 1884.79) pg/ml, P = 0.005]. Patients with the Arg389Arg genotype exhibited a lower ejection fraction than those with the Gly389Gly genotype (54.13 ± 4.94% vs. 57.11 ± 2.87%, P < 0.001). Patients homozygous for Arg389Arg exhibited a higher incidence of ventricular tachycardia and a greater proportion of premature ventricular contraction (PVC) compared to patients homozygous for Gly389Gly (ventricular tachycardia: 19.29% vs. 0.00%, P = 0.009; PVC: 70.00% vs. 40.74%, P = 0.003).

CONCLUSION: The Arg389Arg genotype is associated with greater myocardial damage, impaired cardiac function, and an increased probability of ventricular arrhythmia in AMI patients.

PMID:37102236 | DOI:10.1097/MCA.0000000000001246

Coron Artery Dis. 2023 Jun 1;34(4):227-235. doi: 10.1097/MCA.0000000000001233. Epub 2023 Apr 7.

ABSTRACT

BACKGROUND: Lipoprotein(a) is associated with adverse cardiovascular outcomes and its association with premature coronary artery disease (pCAD) is underexamined. The primary aim of the study is to compare serum lipoprotein(a) levels between pCAD cases and controls.

METHODS: We conducted a systematic review and the MEDLINE database, ClinicalTrials.gov, medRxiv and Cochrane Library were searched for studies evaluating lipoprotein(a) and pCAD. Standardized mean differences (SMD) of lipoprotein(a) in pCAD patients versus the controls were pooled by a random-effects meta-analysis. The presence of statistical heterogeneity was evaluated with the Cochran Q chi-square test and the quality of the included studies was assessed via the Newcastle-Ottawa Scale.

RESULTS: A total of 11 studies were found eligible, reporting on the difference in lipoprotein(a) levels between pCAD patients and controls. Serum lipoprotein(a) concentration was found significantly increased in patients with pCAD (SMD = 0.97; 95% confidence intervals, 0.52-1.42; P < 0.0001; I2 = 98%) as compared to controls. High statistical heterogeneity and relatively small case-control studies of moderate quality are the main limitations of this meta-analysis.

CONCLUSION: Lipoprotein(a) levels are significantly increased in patients with pCAD as compared to controls. Further studies are needed to clarify the clinical significance of this finding.

PMID:37102228 | DOI:10.1097/MCA.0000000000001233

Cancer Med. 2023 Apr 26. doi: 10.1002/cam4.5989. Online ahead of print.

ABSTRACT

BACKGROUND: Patients with certain autoimmune conditions are at a reduced risk of developing breast cancer compared to the general population. Despite this, little is known about outcomes in patients with breast cancer who have a concurrent autoimmune diagnosis.

METHODS: This study compared differences in outcomes between women with breast cancer who had or did not have an autoimmune diagnosis. The SEER-Medicare databases (2007-2014) were used to identify patients with breast cancer and diagnosis codes were used to identify those with an autoimmune disorder.

RESULTS: The studied autoimmune diseases had a prevalence of 27% among the 137,324 patients with breast cancer. Autoimmune disease was associated with significantly longer overall survival (OS) and significantly lower cancer-specific mortality (CSM) among stage IV breast cancer patients (p < 0.0001). After controlling for the effects of age, race, chronic kideny disease, chemotherapy, and radiation therapy autoimmune disease was still predictive of improved OS (HR: 1.45, 95% CI: 1.35-1.55, p < 0.0001) and CSM (HR: 1.40, 95% CI: 1.29-1.5, p < 0.0001). By contrast, in patients with stage I-III breast cancer, the presence of an autoimmune diagnosis was associated with a lower OS (p < 0.0001, p < 0.0001, and p = 0.026, respectively), compared to patients without autoimmune disease.

CONCLUSIONS: We found a higher prevalence of rheumatoid arthritis, Crohn’s disease, ulcerative colitis, and systemic lupus erythematosus in patients with breast cancer compared to age matched cohorts in the general population. The presence of an autoimmune diagnosis was associated with a lower OS in stages I-III breast cancer and improved OS and CSM in patients with stage IV disease. These results suggest that anti-tumor immunity plays an important role in late stage breast cancer and could potentially be exploited to improve the effectiveness of immunotherapy.

PMID:37102221 | DOI:10.1002/cam4.5989

J Cosmet Dermatol. 2023 Apr 26. doi: 10.1111/jocd.15786. Online ahead of print.

ABSTRACT

BACKGROUND: The recent removal of hydroquinone from the over-the-counter market has created a need for modern skin lightening formulations. An effective pigment lightening formulation must be non-irritating to prevent skin darkening from post-inflammatory hyperpigmentation, penetration enhanced to reach the epidermal/dermal junction, contain anti-inflammatory ingredients, and address multiple mechanisms of pigment production.

OBJECTIVE: The objective of this research was to demonstrate the efficacy of a topical multimodal pigment lightening preparation containing tranexamic acid, niacinamide, and licorice.

METHODS: Fifty female subjects 18+ years of all Fitzpatrick skin types with mild to moderate facial dyspigmentation were enrolled. Subjects were provided with the study product for twice daily use on the entire face and an SPF50 sunscreen with evaluations occurring at Week 4, Week 8, Week 12, and Week 16. The investigator used a face map to identify a pigmented target site on the face for dermaspectrophotometer (DSP) measurement. The dermatologist investigator completed a baseline facial efficacy and tolerability assessment. The subjects completed a tolerability assessment.

RESULTS: 48/50 subjects completed the study without tolerability issues. The DSP readings demonstrated a statistically significant reduction in target spot pigmentation at Week 16. The investigator assessed a 37% decrease in pigment intensity, a 31% decrease in pigment extent, a 30% decrease in pigment homogeneity, a 45% improvement in brightness, a 42% improvement in clarity, and a 32% improvement in overall facial skin dyspigmentation at Week 16.

CONCLUSION: The combination of penetration enhanced tranexamic acid, niacinamide, and licorice was effective in inducing facial pigment lightening.

PMID:37102219 | DOI:10.1111/jocd.15786

Scand J Gastroenterol. 2023 Apr 26:1-14. doi: 10.1080/00365521.2023.2200443. Online ahead of print.

ABSTRACT

OBJECTIVE: To systematically evaluate the efficacy and safety of the method of placing the distal stent opening above the duodenal papilla (hereinafter referred to Above method) for endoscopic retrograde stent internal drainage in MBO patients.

METHODS: PubMed, Embase, Web of science and Cochrane databases were searched to identify clinical studies comparing the stent distal opening mounted above the papilla and across the papilla (hereinafter referred to Across method), Comparison indicators included stent patency, stent occlusion rate, clinical success rate, overall complication rate, postoperative cholangitis rate, and overall survival. Revman5.4 software was used for meta-analysis, funnel plot and publication bias and Egger’s test were completed by Stata14.0 software.

RESULTS: A total of 11 clinical studies (8 case-control studies, 3 RCT studies) were included, with a total of 751 patients (318 cases in the Above group and 433 cases Across group). The overall patency of Above method was longer than that of Across method (HR = 0.60, 95%CI [0.46-0.78], p < 0.001). Subgroup analysis showed statistical difference using plastic stent (HR = 0.49, 95%CI [0.33,0.73], p < 0.001). Inversely, there didn’t exist significant difference in which metal stent were adopted (HR= 0.74, 95%CI [0.46,1.18], p = 0.21). Similarly, there also without statistical difference between patients with plastic stent placed above the papilla and metal stent mounted Across the papilla (HR = 0.73, 95%CI [0.15,3.65], p = 0.70). Moreover, the overall complication rate of the Above method was lower than that of the Across method (OR = 0.48,95%CI [0.30,0.75], p = 0.002). On the contrary, the differences of stent occlusion rate (OR = 0.86,95%CI [0.51,1.44], p = 0.56), overall survival (HR = 0.90, 95%CI [0.71,1.13]), p = 0.36), the clinical success rate (OR = 1.30, 95%CI [0.52,3.24], p = 0.57) and postoperative cholangitis rats (OR = 0.73, 95%CI [0.34,1.56], p = 0.41) were not statistically significant.

CONCLUSIONS: The distal opening of the stent can be placed above the duodenal main papilla for eligible MBO patients who receiving endoscopic retrograde stent drainage treatment, which can effectively prolong the patency duration when plastic stent is used, and reduce the overall risk of complications.

PMID:37102215 | DOI:10.1080/00365521.2023.2200443