Category: Nevin Manimala

Urolithiasis. 2024 Jun 19;52(1):94. doi: 10.1007/s00240-024-01577-0.

ABSTRACT

Approximately 80% of kidney stone diseases contain calcium. Inherited genetic factors are among the variables that influence the development of calcium-containing kidney stone diseases (CKSD). Previous genome-wide association studies (GWAS) on stone diseases have been reported worldwide; however, these are not focused on calcium-containing stones. We conducted a GWAS to identify germline genetic polymorphisms associated with CKSD in a Medical Center in Taiwan; hence, this study was based primarily on a hospital-based database. CKSD was diagnosed using the chart records. Patients infected with urea-splitting-microorganisms and those with at least two urinary pH value below 5.5 were excluded. None of the patients had cystic stones based on stone analysis. Those over 40 years of age with no history of CKSD and no microscopic hematuria on urinalysis were considered as controls. The DNA isolated from the blood of 14,934 patients (63.7% male and 36.3% female) with CKSD and 29,868 controls (10,830 men and 19,038 women) at a medical center was genotyped for approximately 714,457 single nucleotide polymorphisms (SNPs) with minor allele frequency of ≥ 0.05. We used PLINK 1.9 to calculate the polygenic risk score (PRS) to investigate the association between CKSD and controls. The accuracy of the PRS was verified by dividing it into the training and testing groups. The statistical analyses were calculated with the area under the curve (AUC) using IBM SPSS version 22. We identified 432 susceptibility loci that reached a genome-wide threshold of P < 1.0 × 10^{– 5}. A total of 132 SNPs reached a threshold of P < 5 × 10^{– 8} using a stricter definition of significance on chromosomes 4, 13, 16, 17, and 18. At the top locus of our study, SNPs in DGKH, PDILT, BCAS3, and ABCG2 have been previously reported. RN7SKP27, HDAC4, PCDH15, AP003068.2, and NFATC1 were novel findings in this study. PRS was adjusted for sex and age, resulting in an AUC of 0.65. The number of patients in the top quartile of PRS was 1.39 folds in the risk of CKSD than patients in the bottom quartile. Our data identified the significance of GWAS for patients with CKSD in a hospital-based study. The PRS also had a high AUC for discriminating patients with CKSD from controls. A total of 132 SNP loci of SNPs significantly associated with the development of CKSD. This first survey, which focused on patients with CKSD, will provide novel insights specific to CKSD and its potential clinical biomarkers.

PMID:38896256 | DOI:10.1007/s00240-024-01577-0

Abdom Radiol (NY). 2024 Jun 19. doi: 10.1007/s00261-024-04419-0. Online ahead of print.

ABSTRACT

PURPOSE: To develop and validate a nomogram model that combines radiomics features, clinical factors, and coagulation function indexes (CFI) to predict intraoperative blood loss (IBL) during cesarean sections, and to explore its application in optimizing perioperative management and reducing maternal morbidity.

METHODS: In this retrospective consecutive series study, a total of 346 patients who underwent magnetic resonance imaging (156 for training and 68 for internal test, center 1; 122 for external test, center 2) were included. IBL+ was defined as more than 1000 mL estimated blood loss during cesarean sections. The prediction models of IBL were developed based on machine-learning algorithms using CFI, radiomics features, and clinical factors. ROC analysis was performed to evaluate the performance for IBL diagnosis.

RESULTS: The support vector machine model incorporating all three modalities achieved an AUC of 0.873 (95% CI 0.769-0.941) and a sensitivity of 1.000 (95% CI 0.846-1.000) in the internal test set, with an AUC of 0.806 (95% CI 0.725-0.872) and a sensitivity of 0.873 (95% CI 0.799-0.922) in the external test set. It was also scored significantly higher than the CFI model (P = 0.035) on the internal test set, and both the CFI (P = 0.002) and radiomics-CFI models (P = 0.007) on the external test set. Additionally, the nomogram constructed based on three modalities achieved an internal testing set AUC of 0.960 (95% CI 0.806-0.999) and an external testing set AUC of 0.869 (95% CI 0.684-0.967) in the pregnant population without a pernicious placenta previa. It is noteworthy that the AUC of the proposed model did not show a statistically significant improvement compared to the Clinical-CFI model in both internal (P = 0.115) and external test sets (P = 0.533).

CONCLUSION: The proposed model demonstrated good performance in predicting intraoperative blood loss (IBL), exhibiting high sensitivity and robust generalizability, with potential applicability to other surgeries such as vaginal delivery and postpartum hysterectomy. However, the performance of the proposed model was not statistically significantly better than that of the Clinical-CFI model.

PMID:38896245 | DOI:10.1007/s00261-024-04419-0

Anal Bioanal Chem. 2024 Jun 19. doi: 10.1007/s00216-024-05380-z. Online ahead of print.

ABSTRACT

The measurement uncertainty is a crucial quantitative parameter for assessing the reliability of the result. The study aimed to propose a new budget for uncertainty evaluation of a reference measurement procedure for the determination of total testosterone in human serum. The adaptive Monte Carlo method (aMCM) was used for the propagation of probability distributions assigned to various input quantities to determine the uncertainty of the testosterone concentration. The basic principles of the propagation and the statistical analysis were described based on the experimental results of the quality control serum sample. The analysis of the number of Monte Carlo trials was discussed. The procedure of validation of the GUM uncertainty framework using the aMCM was also provided. The number of Monte Carlo trials was 2.974 × 10⁶ when the results had stabilized. The total testosterone concentration was 16.02 nmol/L, and the standard uncertainty was 0.30 nmol/L. The coverage interval at coverage probability of 95% was 15.45 to 16.62 nmol/L, while the probability distribution for testosterone concentration was approximately described by a Gaussian distribution. The validation of results was not passed as the expanded uncertainty result obtained by the aMCM was slightly lower, about 7%, than that by the GUM uncertainty framework with consistent results of the concentration.

PMID:38896240 | DOI:10.1007/s00216-024-05380-z

Health Sci Rep. 2024 Jun 17;7(6):e2161. doi: 10.1002/hsr2.2161. eCollection 2024 Jun.

ABSTRACT

BACKGROUND AND AIM: Test-sets are standardized assessments used to evaluate reader performance in breast screening. Understanding how test-set results affect real-world performance can help refine their use as a quality improvement tool. The aim of this study is to explore if mammographic test-set results could identify breast-screening readers who improved their cancer detection in association with test-set training.

METHODS: Test-set results of 41 participants were linked to their annual cancer detection rate change in two periods oriented around their first test-set participation year. Correlation tests and a multiple linear regression model investigated the relationship between each metric in the test-set results and the change in detection rates. Additionally, participants were divided based on their improvement status between the two periods, and Mann-Whitney U test was used to determine if the subgroups differed in their test-set metrics.

RESULTS: Test-set records indicated multiple significant correlations with the change in breast cancer detection rate: a moderate positive correlation with sensitivity (0.688, p < 0.001), a moderate negative correlation with specificity (-0.528, p < 0.001), and a low to moderate positive correlation with lesion sensitivity (0.469, p = 0.002), and the number of years screen-reading mammograms (0.365, p = 0.02). In addition, the overall regression was statistically significant (F (2,38) = 18.456 p < 0.001), with an R² of 0.493 (adjusted R² = 0.466) based on sensitivity (F = 27.132, p < 0.001) and specificity (F = 9.78, p = 0.003). Subgrouping the cohort based on the change in cancer detection indicated that the improved group is significantly higher in sensitivity (p < 0.001) and lesion sensitivity (p = 0.02) but lower in specificity (p = 0.003).

CONCLUSION: Sensitivity and specificity are the strongest test-set performance measures to predict the change in breast cancer detection in real-world breast screening settings following test-set participation.

PMID:38895553 | PMC:PMC11183186 | DOI:10.1002/hsr2.2161

Cereb Cortex. 2024 Jun 4;34(6):bhae252. doi: 10.1093/cercor/bhae252.

ABSTRACT

Neurofeedback, a non-invasive intervention, has been increasingly used as a potential treatment for major depressive disorders. However, the effectiveness of neurofeedback in alleviating depressive symptoms remains uncertain. To address this gap, we conducted a comprehensive meta-analysis to evaluate the efficacy of neurofeedback as a treatment for major depressive disorders. We conducted a comprehensive meta-analysis of 22 studies investigating the effects of neurofeedback interventions on depression symptoms, neurophysiological outcomes, and neuropsychological function. Our analysis included the calculation of Hedges’ g effect sizes and explored various moderators like intervention settings, study designs, and demographics. Our findings revealed that neurofeedback intervention had a significant impact on depression symptoms (Hedges’ g = -0.600) and neurophysiological outcomes (Hedges’ g = -0.726). We also observed a moderate effect size for neurofeedback intervention on neuropsychological function (Hedges’ g = -0.418). As expected, we observed that longer intervention length was associated with better outcomes for depressive symptoms (β = -4.36, P < 0.001) and neuropsychological function (β = -2.89, P = 0.003). Surprisingly, we found that shorter neurofeedback sessions were associated with improvements in neurophysiological outcomes (β = 3.34, P < 0.001). Our meta-analysis provides compelling evidence that neurofeedback holds promising potential as a non-pharmacological intervention option for effectively improving depressive symptoms, neurophysiological outcomes, and neuropsychological function in individuals with major depressive disorders.

PMID:38889442 | DOI:10.1093/cercor/bhae252

Obstet Gynecol. 2024 Jun 18. doi: 10.1097/AOG.0000000000005648. Online ahead of print.

ABSTRACT

OBJECTIVE: To assess the efficacy of topical sildenafil cream, 3.6% among healthy premenopausal women with female sexual arousal disorder.

METHODS: We conducted a phase 2b, exploratory, randomized, placebo-controlled, double-blind study of sildenafil cream. Coprimary efficacy endpoints were the change from baseline to week 12 in the Arousal Sensation domain of the SFQ28 (Sexual Function Questionnaire) and question 14 of the FSDS-DAO (Female Sexual Distress Scale-Desire, Arousal, Orgasm).

RESULTS: Two hundred women with female sexual arousal disorder were randomized to sildenafil cream (n=101) or placebo cream (n=99). A total of 174 participants completed the study (sildenafil 90, placebo 84). Among the intention-to-treat (ITT) population, which included women with only female sexual arousal disorder and those with female sexual arousal disorder with concomitant sexual dysfunction diagnoses or genital pain, although the sildenafil cream group demonstrated greater improvement in the SFQ28 Arousal Sensation domain scores, there were no statistically significant differences between sildenafil and placebo cream users in the coprimary and secondary efficacy endpoints. An exploratory post hoc subset of the ITT population with an enrollment diagnosis of female sexual arousal disorder with or without concomitant decreased desire randomized to sildenafil cream reported significant increases in their SFQ28 Arousal Sensation domain score (least squares mean 2.03 [SE 0.62]) compared with placebo cream (least squares mean 0.08 [SE 0.71], P=.04). This subset achieved a larger mean improvement in the SFQ28 Desire and Orgasm domain scores. This subset population also had significantly reduced sexual distress and interpersonal difficulties with sildenafil cream use as measured by FSDS-DAO questions 3, 5, and 10 (all P≤.04).

CONCLUSION: Topical sildenafil cream improved outcomes among women with female sexual arousal disorder, most significantly in those who did not have concomitant orgasmic dysfunction. In particular, in an exploratory analysis of a subset of women with female sexual arousal disorder with or without concomitant decreased desire, topical sildenafil cream increased sexual arousal sensation, desire, and orgasm and reduced sexual distress.

CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT04948151.

PMID:38889431 | DOI:10.1097/AOG.0000000000005648

Biomol Biomed. 2024 Jun 17. doi: 10.17305/bb.2024.10659. Online ahead of print.

ABSTRACT

The effective iodine-131 (I-131) half-life (EHL) plays an important role in the evaluation of radioactive iodine therapy for Graves’ disease (GD) patients. It has been observed that the EHL of GD patients varies after taking lithium carbonate. The purpose of this study is to investigate whether EHL can be extended and to identify the predictive factors associated with this outcome. The clinical data of 225 GD patients were retrospectively reviewed. Patients were divided into two groups based on whether the ΔEHL was ≥ 0.5 days. EHL tested after lithium carbonate was defined as Li-EHL. In the univariate analysis, age, sex, thyrotropin receptor antibody (TRAb), thyroglobulin antibody (TgAb), thyroid peroxidase antibody (TPOAb), and baseline-EHL exhibited significant differences between the two groups (P < 0.05). Cutoff values of age and baseline-EHL to predict significant EHL extension were 40.5 years and 4.85 days, respectively, as determined by receiver operating characteristic (ROC) curve analysis. Multiple linear regression analysis further revealed that the regression equation, which included age, sex, baseline-EHL, and the FT3, free triiodothyronine (FT4)/free thyroxine(FT3) ratio, was statistically significant (P < 0.05). Li-EHL positively correlated with baseline-EHL and the FT4/FT3 ratio, but negatively correlated with age. Li-EHL was also increased in female individuals. In conclusion, age, sex, baseline-EHL and the FT4/FT3 ratio were associated with Li-EHL in GD patients.

PMID:38889393 | DOI:10.17305/bb.2024.10659

J Clin Oncol. 2024 Jun 18:JCO2301680. doi: 10.1200/JCO.23.01680. Online ahead of print.

ABSTRACT

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.Observational studies have associated aspirin or cyclooxygenase 2 (COX-2) inhibitor usage either before or after colorectal cancer diagnosis with lower risk of recurrence and suggest that PIK3CA mutational status is predictive of better response to COX-2 inhibition. To prospectively test whether adding the COX-2 inhibitor celecoxib to standard adjuvant chemotherapy reduces the risk of recurrence and improves survival, the National Cancer Institute sponsored the CALGB/SWOG 80702 trial (ClinicalTrials.gov identifier: NCT01150045) for patients with stage III resected colon cancer. Although the primary hypothesis for all patients did not show a statistically significant improvement in disease-free survival (DFS) with celecoxib, subgroup analysis by PIK3CA mutational status was a preplanned study. PIK3CA gain-of-function mutations were detected in 259 of 1,197 tumors with available whole-exome sequencing data. When stratified by PIK3CA status, patients with PIK3CA gain-of-function mutations treated with celecoxib exhibited improved DFS (adjusted hazard ratio [HR], 0.56 [95% CI, 0.33 to 0.96]) compared with PIK3CA wildtype patients (adjusted HR, 0.89 [95% CI, 0.70 to 1.14]), although the interaction test was nonsignificant (P_interaction = .13). Overall survival was similarly improved for patients with PIK3CA gain-of-function mutations (adjusted HR, 0.44 [95% CI, 0.22 to 0.85]) compared with PIK3CA wildtype patients (adjusted HR, 0.94 [95% CI, 0.68 to 1.30]; P_interaction = .04). Although the test for heterogeneity in DFS did not reach statistical significance, the results suggest potential utility of PIK3CA to consider selective usage of COX-2 inhibitors in addition to standard treatment for stage III colon cancer.

PMID:38889377 | DOI:10.1200/JCO.23.01680

Am J Audiol. 2024 Jun 18:1-9. doi: 10.1044/2024_AJA-22-00190. Online ahead of print.

ABSTRACT

PURPOSE: The objective of this study was to determine the normative vestibulo-ocular reflex gain output values of the computerized rotational head impulse test (crHIT) with stationary visual targets (earth bound) in healthy participants in each decade age band of life: 10-19, 20-29, 30-39, 40-49, 50-59, 60-69, and 70+ years.

METHOD: Seventy-seven community-dwelling participants (10-85 years of age) with normal lateral semicircular canal (SCC) functioning and no symptoms or history of vestibular dysfunction were recruited through convenience sampling and assessed with the crHIT using stationary targets. These participants were assessed using two standard protocols in a randomized order.

RESULTS: Results from 77 participants (M _age = 46 years; 43 women, 34 men) were analyzed. Pearson’s correlation coefficient and simple linear regression indicated a statistically significant relationship between crHIT gain output and age (p > .05) for right gain, 1030°/s², and left gain, 1005°/s². Although a statistically significant relationship was found, the slope was minor, demonstrating that the clinical effect of age on crHIT gain output was insignificant. Furthermore, no statistically significant relationship exists between crHIT gain output and gender (p > .05). Age-dependent normative data were calculated using the 2.5th and 97.5th confidence interval (CI) percentile method. The responses of angular vestibulo-ocular reflex (aVOR) gain values for crHIT are expected to occur within the range for lower limit reference interval (RI) of 0.85-0.9 and upper limit RI of 1.11-1.18 for 1030°/s² and lower limit RI of 0.86-0.92 and upper limit RI of 1.13-1.16 for 1005°/s². It can be expected that 90% CI of the population with normal lateral SCC functioning will have aVOR gain values that fall within this range.

CONCLUSION: Despite a statistically significant relationship that exists with aVOR gain output and age, the changes are minor, declining by 0.0088 units per 10 years, justifying the same normative data for all decade age bands.

PMID:38889375 | DOI:10.1044/2024_AJA-22-00190