Application of ultrasound-guided percutaneous nephrostomy in the treatment of a solitary kidney with hydronephrosis due to renal tuberculosis.

PURPOSE: To investigate the value of ultrasound-guided percutaneous nephrostomy and nephrostomy tube replacement for treating a solitary kidney with hydronephrosis due to renal tuberculosis. METHODS: Clinical data of patients with a solitary kidney with hydronephrosis caused by renal tuberculosis who underwent ultrasound-guided percutaneous nephrostomy in our hospital from January 2011 to December 2022 were retrospectively analyzed. The associated success rate and complications were statistically analyzed, pre- and post-catheterization changes in serum creatinine and blood urea nitrogen levels were compared, success rate and complications of nephrostomy tube replacement in patients with long-term catheterization were statistically analyzed, and the impact of long-term catheterization on patient life was investigated. RESULTS: Overall, 32 patients aged 17-75 years (average age: 44.1 ± 16.9 years) underwent ultrasound-guided percutaneous nephrostomy. Sixty-three punctures were performed; the puncture success rate was 100%. The levels of serum creatinine and blood urea nitrogen of patients decreased after catheterization, and the differences between the pre-catheterization and post-catheterization were significant (P < 0.05). There were 1, 3, and 12 cases of serious, minor, and fistula-related complications, respectively. The mean duration of the indwelling catheter was 56.7 ± 36.2 (range, 13-120) months. The number of nephrostomy tube replacements was 344 times, and the success rate was 100%. All patients could take care of the puncture point by themselves. CONCLUSION: Ultrasound-guided percutaneous nephrostomy and nephrostomy tube replacement have a high success rate and few complications, which can improve the renal function of patients. It is of great value for treating a solitary kidney with hydronephrosis caused by renal tuberculosis.

Gene-level association analysis of ordinal traits with functional ordinal logistic regressions.

In this paper, we develop functional ordinal logistic regression (FOLR) models to perform gene-based analysis of ordinal traits. In the proposed FOLR models, genetic variant data are viewed as stochastic functions of physical positions and the genetic effects are treated as a function of physical positions. The FOLR models are built upon functional data analysis which can be revised to analyze the ordinal traits and high dimension genetic data. The proposed methods are capable of dealing with dense genotype data which is usually encountered in analyzing the next-generation sequencing data. The methods are flexible and can analyze three types of genetic data: (1) rare variants only, (2) common variants only, and (3) a combination of rare and common variants. Simulation studies show that the likelihood ratio test statistics of the FOLR models control type I errors well and have good power performance. The proposed methods achieve the goals of analyzing ordinal traits directly, reducing high dimensionality of dense genetic variants, being computationally manageable, facilitating model convergence, properly controlling type I errors, and maintaining high power levels. The FOLR models are applied to analyze Age-Related Eye Disease Study data, in which two genes are found to strongly associate with four ordinal traits.

Elevated cytokines and chemokines in peripheral blood of patients with SARS-CoV-2 pneumonia treated with high-titer convalescent plasma.

The global SARS-CoV-2 coronavirus pandemic continues to be devastating in many areas. Treatment options have been limited and convalescent donor plasma has been used by many centers to transfer passive neutralizing antibodies to patients with respiratory involvement. The results often vary by institution and are complicated by the nature and quality of the donor plasma itself, the timing of administration and the clinical aspects of the recipients. SARS-CoV-2 infection is known to be associated with an increase in the blood concentrations of several inflammatory cytokines/chemokines, as part of the overall immune response to the virus and consequential to mediated lung pathology. Some of these correlates contribute to the cytokine storm syndrome and acute respiratory distress syndrome, often resulting in fatality. A Phase IIa clinical trial at our institution using high neutralizing titer convalescent plasma transfer gave us the unique opportunity to study the elevations of correlates in the first 10 days after infusion. Plasma recipients were divided into hospitalized COVID-19 pneumonia patients who did not (Track 2) or did (Track 3) require mechanical ventilation. Several cytokines were elevated in the patients of each Track and some continued to rise through Day 10, while others initially increased and then subsided. Furthermore, elevations in MIP-1α, MIP-1ß and CRP correlated with disease progression of Track 2 recipients. Overall, our observations serve as a foundation for further study of these correlates and the identification of potential biomarkers to improve upon convalescent plasma therapy and to drive more successful patient outcomes.

A Study of Novel Exploratory Tools, Digital Technologies, and Central Nervous System Biomarkers to Characterize Unipolar Depression.

Background: Digital technologies have the potential to provide objective and precise tools to detect depression-related symptoms. Deployment of digital technologies in clinical research can enable collection of large volumes of clinically relevant data that may not be captured using conventional psychometric questionnaires and patient-reported outcomes. Rigorous methodology studies to develop novel digital endpoints in depression are warranted. Objective: We conducted an exploratory, cross-sectional study to evaluate several digital technologies in subjects with major depressive disorder (MDD) and persistent depressive disorder (PDD), and healthy controls. The study aimed at assessing utility and accuracy of the digital technologies as potential diagnostic tools for unipolar depression, as well as correlating digital biomarkers to clinically validated psychometric questionnaires in depression. Methods: A cross-sectional, non-interventional study of 20 participants with unipolar depression (MDD and PDD/dysthymia) and 20 healthy controls was conducted at the Centre for Human Drug Research (CHDR), the Netherlands. Eligible participants attended three in-clinic visits (days 1, 7, and 14), at which they underwent a series of assessments, including conventional clinical psychometric questionnaires and digital technologies. Between the visits, there was at-home collection of data through mobile applications. In all, seven digital technologies were evaluated in this study. Three technologies were administered via mobile applications: an interactive tool for the self-assessment of mood, and a cognitive test; a passive behavioral monitor to assess social interactions and global mobility; and a platform to perform voice recordings and obtain vocal biomarkers. Four technologies were evaluated in the clinic: a neuropsychological test battery; an eye motor tracking system; a standard high-density electroencephalogram (EEG)-based technology to analyze the brain network activity during cognitive testing; and a task quantifying bias in emotion perception. Results: Our data analysis was organized by technology - to better understand individual features of various technologies. In many cases, we obtained simple, parsimonious models that have reasonably high diagnostic accuracy and potential to predict standard clinical outcome in depression. Conclusion: This study generated many useful insights for future methodology studies of digital technologies and proof-of-concept clinical trials in depression and possibly other indications.

Gene-based analysis of bi-variate survival traits via functional regressions with applications to eye diseases.

Genetic studies of two related survival outcomes of a pleiotropic gene are commonly encountered but statistical models to analyze them are rarely developed. To analyze sequencing data, we propose mixed effect Cox proportional hazard models by functional regressions to perform gene-based joint association analysis of two survival traits motivated by our ongoing real studies. These models extend fixed effect Cox models of univariate survival traits by incorporating variations and correlation of multivariate survival traits into the models. The associations between genetic variants and two survival traits are tested by likelihood ratio test statistics. Extensive simulation studies suggest that type I error rates are well controlled and power performances are stable. The proposed models are applied to analyze bivariate survival traits of left and right eyes in the age-related macular degeneration progression.

Genetic Associations with Indoor Tanning Addiction among non-Hispanic White Young Adult Women.

BACKGROUND: Some young people may become addicted to indoor tanning in a manner similar to other forms of addiction, but research on genetic associations with indoor tanning addiction remains limited. PURPOSE: To examine if liabilities in genetic addiction reward pathways and psychiatric comorbidity influence the risk of indoor tanning addiction. METHODS: This was a cross-sectional study with a community sample of 292 non-Hispanic white young adult women aged 18-30 years who reported indoor tanning in the past year. Self-report measures included indoor tanning frequency, appearance orientation, depressive symptoms, and two screeners of tanning addiction. DNA samples were analyzed for 34 single nucleotide polymorphisms (SNPs) in candidate genes in addiction reward pathways. RESULTS: No SNPs were significantly associated with tanning addiction in univariate analyses after multiplicity adjustment. In multivariable analyses adjusting for indoor tanning frequency, appearance orientation, and depressive symptoms, variant genotypes (CC or CT) in two DRD2 dopamine receptor gene SNPs were associated with increased odds of indoor tanning addiction (rs4436578, odds ratio [OR]: 2.30, 95% confidence interval [CI]: 1.11-4.77; rs4648318, OR: 1.95, 95% CI: 1.02-3.72). Variant SNP genotypes interacted with depressive symptoms to increase the risk of indoor tanning addiction: OR: 10.79, 95% CI: 3.25, 35.80, OR: 13.60, 95% CI: 4.13, 44.78, respectively. CONCLUSIONS: This study provides preliminary evidence that DRD2 dopamine receptor gene SNPs are associated with indoor tanning addiction and young women with variant genotypes and elevated depressive symptoms may be at higher risk. These preliminary results support a reward-based model for indoor tanning addiction and warrant further investigation.

Gene-based association analysis of survival traits via functional regression-based mixed effect cox models for related samples.

The importance to integrate survival analysis into genetics and genomics is widely recognized, but only a small number of statisticians have produced relevant work toward this study direction. For unrelated population data, functional regression (FR) models have been developed to test for association between a quantitative/dichotomous/survival trait and genetic variants in a gene region. In major gene association analysis, these models have higher power than sequence kernel association tests. In this paper, we extend this approach to analyze censored traits for family data or related samples using FR based mixed effect Cox models (FamCoxME). The FamCoxME model effect of major gene as fixed mean via functional data analysis techniques, the local gene or polygene variations or both as random, and the correlation of pedigree members by kinship coefficients or genetic relationship matrix or both. The association between the censored trait and the major gene is tested by likelihood ratio tests (FamCoxME FR LRT). Simulation results indicate that the LRT control the type I error rates accurately/conservatively and have good power levels when both local gene or polygene variations are modeled. The proposed methods were applied to analyze a breast cancer data set from the Consortium of Investigators of Modifiers of BRCA1 and BRCA2 (CIMBA). The FamCoxME provides a new tool for gene-based analysis of family-based studies or related samples.

Linear mixed models for association analysis of quantitative traits with next-generation sequencing data.

We develop linear mixed models (LMMs) and functional linear mixed models (FLMMs) for gene-based tests of association between a quantitative trait and genetic variants on pedigrees. The effects of a major gene are modeled as a fixed effect, the contributions of polygenes are modeled as a random effect, and the correlations of pedigree members are modeled via inbreeding/kinship coefficients. F -statistics and χ 2 likelihood ratio test (LRT) statistics based on the LMMs and FLMMs are constructed to test for association. We show empirically that the F -distributed statistics provide a good control of the type I error rate. The F -test statistics of the LMMs have similar or higher power than the FLMMs, kernel-based famSKAT (family-based sequence kernel association test), and burden test famBT (family-based burden test). The F -statistics of the FLMMs perform well when analyzing a combination of rare and common variants. For small samples, the LRT statistics of the FLMMs control the type I error rate well at the nominal levels α = 0.01 and 0.05 . For moderate/large samples, the LRT statistics of the FLMMs control the type I error rates well. The LRT statistics of the LMMs can lead to inflated type I error rates. The proposed models are useful in whole genome and whole exome association studies of complex traits.

Effectiveness of ultrasound-guided percutaneous microwave ablation for symptomatic uterine fibroids: a multicentre study in China.

PURPOSE: To evaluate the clinical efficacy of ultrasound-guided percutaneous microwave ablation (PMWA) therapy for symptomatic uterine fibroids in a multicentre study. MATERIALS AND METHODS: Patients with symptomatic uterine fibroids who underwent PMWA at multiple treatment centres in China between January 2013 and August 2015 were prospectively studied to compare the reduction rate of uterine fibroids, haemoglobin level and uterine fibroid symptom and health-related quality of life questionnaire (UFS-QOL) scores before and at 3, 6 and 12 months after ablation. RESULTS: A total of 311 patients (405 leiomyomas) from eight treatment centres underwent the treatment (age, 29-55 years; mean ± SD, 41 ± 5.11 years). The mean diameter of the myomas ranged from 2.03 to 12.50 cm (mean, 5.10 ± 1.28 cm) and the volume ranged from 4.40 to 1022.14 cm3 (mean, 95.01 ± 70.29 cm3). Forty-eight myomas were identified as FIGO type 1/2 fibroids, 256 as type 3/4 fibroids and 101 as type 5/6 fibroids. The mean ablation rate was 86.6% (54.0-100%). The mean reduction rate was 63.5%, 78.5% and 86.7% at 3, 6 and 12 months posttreatment, respectively. The haemoglobin level increased significantly from 88.84 ± 9.31 g/L before treatment to 107.14 ± 13.32, 116.05 ± 7.66 and 117.79 ± 6.51 g/L at 3, 6 and 12 months posttreatment, respectively (p = .000). The symptom severity score (SSS) and health-related quality of life (HRQL) scores were also significantly improved posttreatment compared with before treatment (p = .000). CONCLUSION: PMWA is an effective, minimally invasive treatment for symptomatic leiomyomas that can significantly improve the quality of life of patients.

Variables associated with vaginal discharge after ultrasound-guided percutaneous microwave ablation for adenomyosis.

Objective The aim of this study was to analyse the significant variables for vaginal discharge after ultrasound-guided percutaneous microwave ablation (PMWA) therapy. Materials and methods PMWA was performed on 117 patients with adenomyosis from October 2012 to July 2014. The presence or absence, colour, quantity and duration of vaginal discharge, which was different from pre-ablation, were recorded within 1 year after PMWA. Patients were categorised into G1 (n = 26, without vaginal discharge), G2 (n = 40, vaginal discharge lasting 1 to 19 days), and G3 (n = 51, vaginal discharge lasting ≥20 days) groups. The potentially correlative variables were analysed. Variables with significant correlations with vaginal discharge post-ablation were identified via binary logistic regression analysis. Results The differences in adenomyosis type, pre-ablation uterine volume, total microwave ablation energy, total non-perfused volume (NPV) and minimum distance from the non-perfused lesion (NPL) margin to the endomyometrial junction (EMJ) among groups were statistically significant (p = 0.005, p = 0.000, p = 0.000, p = 0.005 and p = 0.000, respectively). Minimum distance from the NPL margin to the EMJ was the strongest predictor of vaginal discharge post-ablation with odds ratio (OR) 0.632, p = 0.018, 95% CI 0.432-0.923. Patients with diffuse adenomyosis were more likely to have prolonged vaginal discharge (≥20 days) post-ablation (OR 3.461, p = 0.000, 95% CI 1.759-7.536). Conclusion The minimum distance from the NPL margin to the EMJ and adenomyosis type were significantly associated with vaginal discharge post-ablation.

Ultrasound-guided percutaneous microwave ablation for adenomyosis: efficacy of treatment and effect on ovarian function.

A total of 142 premenopausal women with symptomatic adenomyosis underwent ultrasound (US)-guided percutaneous microwave ablation (PMWA) at the Chinese PLA General Hospital. This study aimed to evaluate changes in serum pituitary, gonadal hormone and cancer antigen 125 (CA125) levels after US-guided PMWA. Therefore, estradiol (E2), follicle-stimulating hormone (FSH), prolactin (PRL) and CA125 levels were evaluated before ablation and at 3, 6, 9 and 12 months after ablation. No significant differences were observed in the E2 and FSH levels pre-ablation and during follow-up (E2: p=0.933, p=0.987, p=0.106, p=0.936; FSH: p=0.552, p=0.295, p=0.414, p=0.760). The mean absolute values of serum CA125 and PRL were significantly decreased at 3, 6, 9 and 12 months after ablation (CA125: p<0.001, p<0.001, p<0.001, p=0.003; PRL: p<0.001, p<0.001, p<0.001, p<0.001). A significant correlation between changes in CA125 levels and uterine volume was found (p<0.001). No evidence of a decline in ovarian function was observed after US-guided PMWA.

Ultrasound-guided percutaneous microwave ablation for symptomatic uterine fibroid treatment--a clinical study.

OBJECTIVE: The aim of this study was to assess the feasibility, safety and therapeutic effects of ultrasound (US)-guided percutaneous microwave thermal ablation (PMTA) in situ for the treatment of symptomatic uterine fibroid. MATERIALS AND METHODS: The microwave (MW) antenna was percutaneously inserted into the fibroid under US guidance to perform the ablation. The ultrasound images, any complications and side effects were assessed during and after ablation. The shrinkage rate of the fibroid was calculated after the treatment. RESULTS: Forty patients underwent the treatment. The baseline fibroid volume was 14.6 to 341.1 cm(3) (mean 140.1 ± 87.4 cm(3)). When the MW therapy started, a heightened echo around the MW emission aperture of the antenna was observed and gradually propagated throughout the fibroid while the ablation continued. The mean ablation time was 490 s. Contrast enhanced MRI showed no enhancement in the fibroid post-ablation. The shrinkage rate of the fibroid was 61.8%, 78.7%, 73.2% and 93.1% at 3, 6, 9, and 12 months after ablation, respectively. Six patients felt pain in their lower abdomens or waists within 12 hours post-ablation, and the discomfort rapidly disappeared. Seven patients had a small amount of vaginal bloody secretions within one to two weeks after treatment, and six of these patients recovered from the bleeding without any therapy after one week. No patient developed complications and fever during or after the ablation. CONCLUSIONS: PMTA for fibroid is feasible and safe, and it is an easy and fast procedure that is minimally invasive.

[The study of follow up of percutaneous microwave ablation for uterine fibroids treatment].

OBJECTIVE: To study the prognosis of fibroid after ultrasound-guidance percutaneous microwave ablation (PMAUF). METHODS: From Mar. 2007 to Jul.2010 forty uterine fibroids in forty patients with symptoms which were diagnosed in our hospital accepted PMAUF. One day after treatment blood supply within the fibroid was evaluated, by enhanced MRI. The size of fibroid was measured by ultrasonography in one year with 3 months interval, the monthly menstrual of patient was followed and the mass discharge through vagina were collected for pathological examination. RESULTS: Among the 40 fibroid nodules, 22 are intramural fibroids, 15 subserosal fibroids and 3 submucosal fibroids. The baseline mean diameter of the fibroids ranged from (3.7 to 9.0) cm, with an average of (6.4 ± 1.5) cm. The mean volume ranged from (14.6 - 341.1) cm(3), with an average of (140.1 ± 87.4) cm(3). Three months after treatment, the anechoic zone was observed within the ablated nodules and disappeared in six to seven months. the echo of ablated zone keep higher than the surrounding tissue, whereas the size of fibroid shrank significantly. Meat tissue was discharged from vagina in 8 patients (2 cases of submucosal fibroids, 6 cases intramural fibroids) in the period of menstrual in 1 - 8 months after ablation. The largest dimension of the discharge was 2.1 cm. Pathological examination confirmed the discharges as necrotic fibroid. The patients with subserosal fibroid had no discharge of necrotic tissue. The fibroid shrink rate was higher in the patients with vaginal discharges than that without vaginal discharges (P < 0.01). CONCLUSIONS: After PMAUF necrotic tissue of submucosal and intramural fibroids can be discharged through vagina, liquefaction in the center of subserosal and intramural fibroids may occur and be absorbed gradually, that may be the main reasons for fibroids reduced significantly or disappearance.