Clinical Validation Research Articles

Pulmonary surfactant impacts in vitro activity of selected antifungal drugs against Candida krusei and Candida albicans.

This study investigates how surfactants affect the in-vitro anti-infective efficacy of micafungin, caspofungin, anidulafungin, and amphotericin B in treating pulmonary mycoses. MIC values for antifungal agents were determined against Candida krusei (now Pichia kudriavzevii) ATCC 6258, Candida albicans ATCC 90028, and 18 clinical isolates using the broth microdilution method in RPMI medium, following EUCAST recommendations. MIC assays included testing with and without Curosurf® surfactant at 1mg/mL for C. krusei ATCC 6258 and all C. krusei isolates. Subsequent Time-kill studies in Sabouraud broth involved testing both C. albicans ATCC 90028 and C. krusei ATCC 6258 strains at concentrations equal their respective MIC values, with and without surfactant, using all four antifungals. CFU/mL were assessed at multiple time points up to 24h. TKCs with different surfactant concentrations for C. krusei ATCC 6258 and mini-TKCs at various concentrations relative to the MIC of C. krusei isolates and the reference strain were conducted with micafungin, anidulafungin, and caspofungin. MIC results showed that 1µg/mL surfactant reduced killing of micafungin and anidulafungin against C. krusei, while caspofungin was unaffected. Amphotericin B's MIC decreased by half. TKCs demonstrated significant effects of surfactant on micafungin and anidulafungin against C. krusei, with complete abolition of anidulafungin's activity against C. albicans. This in-vitro study highlights the concentration-dependent inhibitory effect of surfactant on antifungal activity against C. krusei and, to some extent, C. albicans, necessitating further clinical validation for invasive lung mycoses treatment.

A Cell-free DNA Blood-Based Test for Colorectal Cancer Screening

BackgroundColorectal cancer is the third most diagnosed cancer in adults in the United States. Early detection could prevent more than 90% of colorectal cancer–related deaths, yet more than one third of the screening-eligible population is not up to date with screening despite multiple available tests. A blood-based test has the potential to improve screening adherence, detect colorectal cancer earlier, and reduce colorectal cancer–related mortality.MethodsWe assessed the performance characteristics of a cell-free DNA (cfDNA) blood-based test in a population eligible for colorectal cancer screening. The coprimary outcomes were sensitivity for colorectal cancer and specificity for advanced neoplasia (colorectal cancer or advanced precancerous lesions) relative to screening colonoscopy. The secondary outcome was sensitivity to detect advanced precancerous lesions.ResultsThe clinical validation cohort included 10,258 persons, 7861 of whom met eligibility criteria and were evaluable. A total of 83.1% of the participants with colorectal cancer detected by colonoscopy had a positive cfDNA test and 16.9% had a negative test, which indicates a sensitivity of the cfDNA test for detection of colorectal cancer of 83.1% (95% confidence interval [CI], 72.2 to 90.3). Sensitivity for stage I, II, or III colorectal cancer was 87.5% (95% CI, 75.3 to 94.1), and sensitivity for advanced precancerous lesions was 13.2% (95% CI, 11.3 to 15.3). A total of 89.6% of the participants without any advanced colorectal neoplasia (colorectal cancer or advanced precancerous lesions) identified on colonoscopy had a negative cfDNA blood-based test, whereas 10.4% had a positive cfDNA blood-based test, which indicates a specificity for any advanced neoplasia of 89.6% (95% CI, 88.8 to 90.3). Specificity for negative colonoscopy (no colorectal cancer, advanced precancerous lesions, or nonadvanced precancerous lesions) was 89.9% (95% CI, 89.0 to 90.7).ConclusionsIn an average-risk screening population, this cfDNA blood-based test had 83% sensitivity for colorectal cancer, 90% specificity for advanced neoplasia, and 13% sensitivity for advanced precancerous lesions. (Funded by Guardant Health; ECLIPSE ClinicalTrials.gov number, NCT04136002.)

Clinical Validation of Nuclear Factor Kappa B (p65) Among Head and Neck Cancer Patients at One Institution

Clinical Validation of Nuclear Factor Kappa B (p65) Among Head and Neck Cancer Patients at One Institution

Development and clinical validation of a seven-gene signature based on tumor stem cell-related genes to predict ovarian cancer prognosis

ObjectiveTumors are highly heterogeneous, and within their parenchyma, a small population of tumor-stem cells possessing differentiation potential, high oncogenicity, and self-renewal capabilities exists. These cells are pivotal in mediating tumor development, chemotherapy resistance, and recurrence. Ovarian cancer shares characteristics with tumor stem cells, making it imperative to investigate molecular markers associated with these cells.MethodsStem cell-related genes were collected, and molecular subtypes were established based on gene expression profiles from The Cancer Genome Atlas using the R package tool “ConsensusClusterPlus.” Multi-gene prognostic markers were identified using LASSO regression analysis. Gene set enrichment analysis was employed to gain insights into the potential molecular mechanisms of these identified markers. The robustness of these prognostic markers was analyzed across different cohorts, and their clinical independence was determined through multivariate Cox analysis. A nomogram was constructed to assess the model’s clinical applicability. Immunohistochemistry was performed to validate the expression of hub genes.ResultsUtilizing 49 tumor stem cell-related genes associated with prognosis, 362 ovarian cancer samples were divided into two distinct clusters, revealing significant prognostic disparities. A seven-gene signature (GALP, CACNA1C, COL16A1, PENK, C4BPA, PSMA2, and CXCL9), identified through LASSO regression, exhibited stability and robustness across various platforms. Multivariate Cox regression analysis confirmed the signature’s independence in predicting survival in patients with ovarian cancer. Furthermore, a nomogram combining the gene signature demonstrated strong predictive abilities. Immunohistochemistry results indicated significantly elevated GALP, CACNA1C, COL16A1, PENK, C4BPA, PSMA2, and CXCL9 expression in cancer tissues.ConclusionThe seven-gene signature holds promise as a valuable tool for decision-making and prognosis prediction in patients with ovarian cancer.

Assay Validation of Cell-Free DNA Shallow Whole-Genome Sequencing to Determine Tumor Fraction in Advanced Cancers

Blood-based liquid biopsy is increasingly used in clinical care of patients with cancer, and fraction of tumor-derived DNA in circulation (tumor fraction; TFx) has demonstrated clinical validity across multiple cancer types. To determine TFx, shallow whole-genome sequencing of cell-free DNA (cfDNA) can be performed from a single blood sample, using an established computational pipeline (ichorCNA), without prior knowledge of tumor mutations, in a highly cost-effective manner. We describe assay validation of this approach to facilitate broad clinical application, including evaluation of assay sensitivity, precision, repeatability, reproducibility, pre-analytic factors, and DNA quality/quantity. Sensitivity to detect TFx of 3% (lower limit of detection) was 97.2% to 100% at 1× and 0.1× mean sequencing depth, respectively. Precision was demonstrated on distinct sequencing instruments (HiSeqX and NovaSeq) with no observable differences. The assay achieved prespecified 95% agreement of TFx across replicates of the same specimen (repeatability) and duplicate samples in different batches (reproducibility). Comparison of samples collected in EDTA and Streck tubes from single venipuncture in 23 patients demonstrated that EDTA or Streck tubes were comparable if processed within 8 hours. On the basis of a range of DNA inputs (1 to 50 ng), 20 ng cfDNA is the preferred input, with 5 ng minimum acceptable. Overall, this shallow whole-genome sequencing of cfDNA and ichorCNA approach offers sensitive, precise, and reproducible quantitation of TFx, facilitating assay application in clinical cancer care.

Circulating Tumor DNA (ctDNA) and Its Role in Gynecologic Malignancies.

Circulating tumor DNA (ctDNA) refers to small fragments of DNA released into the bloodstream by cancer cells. It is obtained through "liquid biopsy;" which most commonly refers to plasma or blood samples, but can be obtained from a number of bodily fluids including ascitic fluid, saliva, and even urine and stool. ctDNA is detected via polymerase chain reaction (PCR) or next-generation sequencing (NGS). The DNA from these samples is analyzed for the detection of point mutations, copy-number alterations, gene fusion, and DNA methylation. These results have the potential for use in cancer diagnosis, determining prognosis, targeting gene-specific therapies, and monitoring for/predicting disease recurrence and response to treatment. ctDNA offers an alternative to tissue biopsy; it is less invasive and can be monitored serially over time without multiple procedures. Moreover it may have the ability to detect disease recurrence or predict behavior in a way that solid tissue biopsies, tumor marker surveillance, and imaging cannot. Recent explosion in interest in ctDNA shows promising developments for widespread adoption of these techniques in cancer care. However, the use of ctDNA in diagnosis and treatment of gynecologic malignancies is currently limited, compared to adoption in other solid-organ tumors such as breast and colorectal cancers. Compared to other cancer types, there appear to be fewer comprehensive studies and clinical validations specifically focusing on the use of ctDNA in gynecologic cancers. More research is needed in this area to advance the potential for use of ctDNA in ovarian, endometrial, and cervical cancers before this can be routinely adopted to improve care for patients with gynecologic malignancies.

On building machine learning models for medical dataset with correlated features

Abstract This work builds machine learning models for the dataset generated using a numerical model developed on an idealized human artery. The model has been constructed accounting for varying blood characteristics as it flows through arteries with variable vascular properties, and it is applied to simulate blood flow in the femoral and its continued artery. For this purpose, we designed a pipeline model consisting of three components to include the major segments of the femoral artery: CFA, the common femoral artery and SFA, the superficial artery, and its continued one, the popliteal artery (PA). A notable point of this study is that the features and target variables of the former component pipe form the set of features of the latter, thus resulting in multicollinearity among the features in the third component pipe. Thus, we worked on understanding the effect of these correlated features on the target variables using regularized linear regression models, ensemble, and boosting algorithms. This study highlighted the blood velocity in CFA as the primary influential factor for wall shear stress in both CFA and SFA. Additionally, it established the blood rheology in PA as a significant factor for the same in it. Nevertheless, because the study relies on idealized conditions, these discoveries necessitate thorough clinical validation.

Concurrent and Discriminant Validity of the Farsi Translation of the Social Responsiveness Scale-Second Edition (SRS-2) and Social Communication Questionnaire (SCQ).

Objective: Early detection of autism spectrum disorder (ASD) can lead to earlier intervention and greater improvement of children's quality of life and performance; hence, the use of screening tools is essential to facilitate the diagnosis process. The aim of the present study was to determine the clinical and differential validity of Social Responsiveness Scale-Second Edition (SRS-2) and Social Communication Questionnaire (SCQ) in a group of children and adolescents with autism spectrum disorder compared to a normal developmental group. Method : The study was conducted in Roozbeh Hospital involving 52 children with ASD and 53 typically developing (TD) children, aged between 4-12 years. Their parents completed the SRS-2 and SCQ. These children were also interviewed using the Childhood Autism Rating Scale, 2nd Edition (CARS-2) and Asperger Syndrome Diagnostic Scale (ASDS). After completion, the results were analyzed using the SPSS Version 18 software and a significant level of 0.05. Results: The average age of children in the autism group was 7.5 ± 2.7 years, while in the typically developing (TD) children group, it was 7.7 ± 2.3 years (P = 0.656). A positive correlation coefficient was observed between the CARS questionnaire score, the SRS questionnaire score, the SCQ questionnaire score, and the ASDS ‏(P < 0.01). In the SRS questionnaire, the area under the ROC curve was 0.976, and in the SCQ questionnaire it was 0.953, both of which had a good and significant diagnostic value (P < 0.001). A sensitivity of 0.942 and specificity of 0.811 for the cut-off point of 62.5 were obtained in the SRS questionnaire. Additionally, a sensitivity of 0.865 and specificity of 0.925 for the cut-off point of 15.5 were achieved in the SCQ questionnaire. Conclusion: The SRS-2 and the SCQ are sensitive and specific tools for identifying and discriminating children with autism spectrum disorder.

Validation of the Meditech ABPM-06 24-hour blood pressure monitoring system in a pediatric population according to International Organization for Standardization Protocol 81060-2:2018.

Ambulatory blood pressure monitoring (ABPM) devices play a crucial role in diagnosing hypertension, not only in adults but also in pediatric patients. ABPM-06, the latest oscillometric device from Meditech Ltd. (Budapest, Hungary), is the focus of this study. The objective was to validate the ABPM-06 device using the International Organization for Standardization (ISO) 81060-2 : 2018 standard. A total of 86 healthy patients, consisting of 34 males and 52 females, aged between 3 and 17 years, were enrolled in this study. During the ambulatory phase, a total of 50 patients were enrolled, with 35 patients falling within the 3- to 12-year-old age range and 15 patients aged between 12 and 17 years. Additionally, for the dynamic test, 36 patients were selected, comprising of 10 individuals aged 3-12 years and 26 patients aged 12-17 years. These patients were recruited from the outpatient clinics of the Department of Pediatrics at Albert Szent-Györgyi University in Szeged, Hungary. The validation process involved utilizing the same-arm sequence protocol, both in resting positions and during stress testing. The ABPM-06 performed well in both clinical and ambulatory validations. In terms of validation criterion 1, the mean ± SD of the differences between the test device and reference blood pressure readings was -1.3 ± 3.5 mmHg for systolic and -0.1 ± 2.3 mmHg for diastolic, in children under the age of 12 years. For those over the age of 12 years, the mean ± SD of the differences was -2.8 ± 4.6 mmHg for systolic and -0.5 ± 2.7 mmHg for diastolic. Regarding the ambulatory validation, for children under 12 years old, the mean ± SD of the differences was -1.3 ± 3.5 mmHg for systolic and -0.1 ± 2.3 mmHg for diastolic. In the age group above 12 years, the mean ± SD of the differences was -2.8 ± 4.6 mmHg for systolic and -0.5 ± 2.7 mmHg for diastolic. Both tests successfully met the established criteria regarding the mean and SD values of the differences between the device readings and the observed SBP and DBP measurements. The ABPM-06 oscillometric device fully adheres to the ISO 81060-2 : 2018 standard requirements for ABPM determination in the pediatric population (ages 3-17 years). Consequently, this ABPM device proves to be suitable for effectively managing hypertension in children and adolescents.

Semi-automatic proximal humeral trabecular bone density assessment tool: technique application and clinical validation.

This study aimed to apply a newly developed semi-automatic phantom-less QCT (PL-QCT) to measure proximal humerus trabecular bone density based on chest CT and verify its accuracy and precision. Subcutaneous fat of the shoulder joint and trapezius muscle were used as calibration references for PL-QCT BMD measurement. A self-developed algorithm based on a convolution map was utilized in PL-QCT for semi-automatic BMD measurements. CT values of ROIs used in PL-QCT measurements were directly used for phantom-based quantitative computed tomography (PB-QCT) BMD assessment. The study included 376 proximal humerus for comparison between PB-QCT and PL-QCT. Two sports medicine doctors measured the proximal humerus with PB-QCT and PL-QCT without knowing each other's results. Among them, 100 proximal humerus were included in the inter-operative and intra-operative BMD measurements for evaluating the repeatability and reproducibility of PL-QCT and PB-QCT. A total of 188 patients with 376 shoulders were involved in this study. The consistency analysis indicated that the average bias between proximal humerus BMDs measured by PB-QCT and PL-QCT was 1.0 mg/cc (agreement range - 9.4 to 11.4; P > 0.05, no significant difference). Regression analysis between PB-QCT and PL-QCT indicated a good correlation (R-square is 0.9723). Short-term repeatability and reproducibility of proximal humerus BMDs measured by PB-QCT (CV: 5.10% and 3.41%) were slightly better than those of PL-QCT (CV: 6.17% and 5.64%). We evaluated the bone quality of the proximal humeral using chest CT through the semi-automatic PL-QCT system for the first time. Comparison between it and PB-QCT indicated that it could be a reliable shoulder BMD assessment tool with acceptable accuracy and precision. This study developed and verify a semi-automatic PL-QCT for assessment of proximal humeral bone density based on CT to assist in the assessment of proximal humeral osteoporosis and development of individualized treatment plans for shoulders.

AI supported fetal echocardiography with quality assessment

This study aimed to develop a deep learning model to assess the quality of fetal echocardiography and to perform prospective clinical validation. The model was trained on data from the 18–22-week anomaly scan conducted in seven hospitals from 2008 to 2018. Prospective validation involved 100 patients from two hospitals. A total of 5363 images from 2551 pregnancies were used for training and validation. The model's segmentation accuracy depended on image quality measured by a quality score (QS). It achieved an overall average accuracy of 0.91 (SD 0.09) across the test set, with images having above-average QS scoring 0.97 (SD 0.03). During prospective validation of 192 images, clinicians rated 44.8% (SD 9.8) of images as equal in quality, 18.69% (SD 5.7) favoring auto-captured images and 36.51% (SD 9.0) preferring manually captured ones. Images with above average QS showed better agreement on segmentations (p < 0.001) and QS (p < 0.001) with fetal medicine experts. Auto-capture saved additional planes beyond protocol requirements, resulting in more comprehensive echocardiographies. Low QS had adverse effect on both model performance and clinician’s agreement with model feedback. The findings highlight the importance of developing and evaluating AI models based on ‘noisy’ real-life data rather than pursuing the highest accuracy possible with retrospective academic-grade data.

Clinical validation of the self-reported 6-item Hamilton Depression Rating Scale (HAM-D6-SR) among inpatients

BackgroundBrief and valid patient-rated symptom scales represent a valuable addition to clinician-rated scales for assessing depression. Studies on the psychometric properties of the self-rated 6-item Hamilton Depression Rating Scale (HAM-D6-SR) have shown promising results for outpatients with depression. The aim of the present study was to evaluate the psychometric properties of the HAM-D6-SR among inpatients using the clinician-rated 17-item Hamilton Rating Scale for Depression (HAMD17) as the gold standard. MethodsInpatients with unipolar or bipolar depression completed the HAM-D6-SR and were subsequently rated on the HAM-D17 by trained raters, who were blind to the HAM-D6-SR ratings. The pairs of HAM-D6-SR and HAM-D17 ratings were completed twice during admission to evaluate responsiveness over time. Agreement between the HAM-D6-SR and the clinician-rated HAM-D17–derived HAM-D6 was evaluated using the intraclass correlation coefficient (ICC). Responsiveness was evaluated by means of the Spearman's rank correlation coefficient (rho). ResultsA total of 102 participants completed the HAM-D6-SR at least once (median age: 41 years; 66 % females). The ICC for the HAM-D6-SR and the HAM-D17–derived HAM-D6 was 0.60 (95%CI = 0.30–0.76), with the ICC at the item level ranging from 0.13 (Psychomotor retardation) to 0.75 (Depressed mood). The correlation between the changes in the baseline–endpoint total scores on the HAM-D6-SR and HAM-D17-derived HAM-D6 was rho = 0.59 (p < 0.001). LimitationsTest-retest reliability and structural validity were not evaluated. ConclusionsThe HAM-D6-SR holds promise as a valid self-report of core depressive symptoms among inpatients and may aid treatment decisions. However, the validity of self-reported psychomotor retardation was poor.

Associations between cytokines and the risk of female and male infertility: A two-sample Mendelian randomization analysis

PurposeObservational studies have linked cytokines to the occurrence of female and male infertility. However, it is not clear how biomarkers of inflammation are causally related to infertility. To explore whether genetic variants in circulating cytokines are associated with the pathogenesis of infertility, we performed two-sample Mendelian randomization (MR) analysis. MethodsA total of 31,112 individuals of European ancestry were included in a genome-wide association study (GWAS) of 47 circulating cytokines as instrumental variables (IVs). Outcome data were female infertility, including four different subtypes, and male infertility, from the FinnGen consortium. Five MR methods, including inverse-variance weighted (IVW), MR-Egger, simple mode, weighted median, and weighted mode were employed to examine the genetic association between cytokines and the risk of female infertility and male infertility. The false discovery rate (FDR) was controlled using the Benjamini–Hochberg method. ResultsAfter FDR correction, cis-protein quantitative trait locus (cis-pQTL) instruments showed that the cytokines GROa and MCSF were positively associated with female infertility. In analyses of subtypes of female infertility, eotaxin and sICAM were inversely associated with ovulation-related infertility; MCP3 alone was positively associated with uterus-related infertility; GROa and MCSF were positively correlated with infertility of cervical, vaginal, and other or unspecified origin; and MIP1a was negatively correlated with tubal origin infertility. The cytokines HGF, IL-2ra, and RANTES were positively correlated with male infertility. Similar findings were obtained in sensitivity analyses. There was no evidence of pleiotropy or heterogeneity in the results. ConclusionThese findings contribute to current understanding of the role of cytokine biomarkers in the etiology of female and male infertility. Furthermore clinical experimental validation is required to evaluate the potential of these cytokines as biomarkers.

Long noncoding RNAs and circular RNAs as potential diagnostic biomarkers of inflammatory bowel diseases: a systematic review and meta-analysis.

Inflammatory bowel disease (IBD) poses a growing global burden, necessitating the discovery of reliable biomarkers for early diagnosis. The clinical significance of dysregulated expression of long noncoding RNAs (lncRNAs) and circular RNAs (circRNAs) in diagnosing IBD has not been well established. Thus, our study aimed to investigate the diagnostic value of lncRNAs and circRNAs for IBD based on currently available studies. A comprehensive search was carried out in diverse electronic databases, such as PubMed, Embase, Scopus, Science Direct and Wiley Online Library to retrieve articles published until October 30, 2023. Stata 17.0 software was employed to determine pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic ratio (DOR), and area under the curve (AUC). Heterogeneity, subgroup analysis, and meta-regression were explored, and publication bias was assessed using Deeks' funnel plot. Fagan's nomogram and likelihood ratio scattergram were employed to evaluate the clinical validity. A total of 11 articles encompassing 21 studies which involved 1239 IBD patients and 985 healthy controls were investigated. The findings revealed lncRNAs exhibit high level of pooled sensitivity 0.94 (95% CI: 0.87-0.97) and specificity 0.99 (95% CI: 0.89-1.00), along with PLR, NLR, DOR, and AUC values of 64.25 (95% CI: 7.39-558.66), 0.06 (95% CI: 0.03-0.13), 1055.25 (95% CI: 70.61-15770.77), and 0.99 (95% CI: 0.97-0.99), respectively. Conversely, CircRNAs showed moderate accuracy in IBD diagnosis, with sensitivity of 0.68 (95% CI: 0.61-0.73), specificity of 0.73 (95% CI: 0.65-0.79), PLR of 2.47 (95% CI: 1.94-3.16), NLR of 0.45 (95% CI: 0.38-0.53), DOR of 5.54 (95% CI: 3.88-7.93), and AUC value of 0.75 (95% CI: 0.71-0.79). Moreover, findings from subgroup analysis depicted heightened diagnostic efficacy when employing lncRNA H19 and a large sample size (≥100), with notable efficacy in diagnosing both ulcerative colitis (UC) and Crohn's disease (CD). LncRNAs exhibit high diagnostic accuracy in distinguishing patients with IBD from healthy controls signifying their possible use as potential biomarkers, while circRNAs showed moderate diagnostic accuracy. Nevertheless, to validate our findings and confirm the clinical utility of lncRNAs and circRNAs in IBD diagnosis, a large pool of prospective and multi-center studies should be undertaken. https://www.crd.york.ac.uk/PROSPERO, identifier CRD42023491840.

Uremic Toxins and Inflammation: Metabolic Pathways Affected in Non-Dialysis-Dependent Stage 5 Chronic Kidney Disease.

Chronic kidney disease (CKD) affects approximately 12% of the global population, posing a significant health threat. Inflammation plays a crucial role in the uremic phenotype of non-dialysis-dependent (NDD) stage 5 CKD, contributing to elevated cardiovascular and overall mortality in affected individuals. This study aimed to explore novel metabolic pathways in this population using semi-targeted metabolomics, which allowed us to quantify numerous metabolites with known identities before data acquisition through an in-house polar compound library. In a prospective observational design with 50 patients, blood samples collected before the initial hemodialysis session underwent liquid chromatography and high-resolution mass spectrometer analysis. Univariate (Mann-Whitney test) and multivariate (logistic regression with LASSO regularization) methods identified metabolomic variables associated with inflammation. Notably, adenosine-5'-phosphosulfate (APS), dimethylglycine, pyruvate, lactate, and 2-ketobutyric acid exhibited significant differences in the presence of inflammation. Cholic acid, homogentisic acid, and 2-phenylpropionic acid displayed opposing patterns. Multivariate analysis indicated increased inflammation risk with certain metabolites (N-Butyrylglycine, dimethylglycine, 2-Oxoisopentanoic acid, and pyruvate), while others (homogentisic acid, 2-Phenylpropionic acid, and 2-Methylglutaric acid) suggested decreased probability. These findings unveil potential inflammation-associated biomarkers related to defective mitochondrial fatty acid beta oxidation and branched-chain amino acid breakdown in NDD stage 5 CKD, shedding light on cellular energy production and offering insights for further clinical validation.

Neuropathic pain after surgery - A clinical validation study and assessment of accuracy measures of the 5-item NeuPPS scale.

The aim of this study was to validate the Neuropathic Pain for Post-Surgical Patients (NeuPPS) scale against clinically verified neuropathic pain (NP) by quantitative sensory testing (QST) as well as evaluation of other psychometric properties. The NeuPPS is a validated 5-item scale designed to evaluate NP in surgical populations. Data from 537 women aged >18 years scheduled for primary breast cancer surgery enrolled in a previous study for assessing risk factors for persistent pain after breast cancer treatment were used. Exclusion criteria were any other breast surgery or relevant comorbidity. A total of 448 eligible questionnaires were available at 6 months and 455 at 12 months. At 12 months, 290 patients completed a clinical examination and QST. NeuPPS and PainDETECT were analyzed against patients with and without clinically verified NP. NP was assessed using a standardized QST protocol including a clinical assessment. Furthermore, the NeuPPS and PainDETECT scores were psychometrically tested with an item response theory method, the Rasch analysis, to assess construct validity. Primary outcomes were the diagnostic accuracy measures for the NeuPPS, and secondary measures were psychometric analyses of the NeuPPS after 6 and 12 months. PainDETECT was also compared to clinically verified NP as well as NeuPPS comparing the stability of the estimates. Comparing the NeuPPS scores with verified NP using a receiver operating characteristic curve, the NeuPPS had an area under the curve of 0.80. Using a cutoff of 1, the NeuPPS had a sensitivity of 88% and a specificity of 59%, and using a cutoff of 3, the values were 35 and 96%, respectively. Analysis of the PainDETECT indicated that the used cutoffs may be inappropriate in a surgical population. The present study supports the validity of the NeuPPS as a screening tool for NP in a surgical population.

Validation of the ACSID-11 for consistent screening of specific Internet-use disorders based on ICD-11 criteria for gaming disorder: A multitrait-multimethod approach

IntroductionWith the inclusion of gaming disorder in the ICD-11, diagnostic criteria were introduced for this relatively new disorder. These criteria may be applied to other potential specific Internet-use disorders. The 11-item Assessment of Criteria for Specific Internet-use Disorders (ACSID-11) was developed for consistent screening of gaming disorder, online buying-shopping disorder, online pornography-use disorder, social networks-use disorder, and online gambling disorder. This study tested the construct validity of the ACSID-11, including convergent and divergent measures. MethodsThe ACSID-11 measures five behavioral addictions with the same set of items by following the principles of the Alcohol, Smoking and Substance Involvement Screening Test (ASSIST). The ACSID-11 was administered to a convenience sample of active Internet users (N = 1597) together with validated and established measures of each specific Internet-use disorder along with screeners for mental health. Included are the Ten-Item Internet Gaming Disorder Test (IGDT-10), the Bergen Shopping Addiction Scale (BSAS), the Problematic Pornography Consumption Scale (PPCS), the Bergen Social Media Addiction Scale (BSMAS) and the Berlin Inventory of Gambling behavior – Screening (BIG-S). The ACSID-11 was compared convergently and divergently through a multitrait-multimethod approach along with contingency tables with the other Internet-use disorder screeners. ResultsThe multitrait-multimethod results shows that each behavior assessed with the ACSID-11 has moderate to strong correlations (r's from 0.462 to 0.609) with the scores of the corresponding established measures and, furthermore, positive correlations (r's from 0.122 to 0.434) with measures of psychological distress and further shows that the ACSID-11 can be used for a comprehensive assessment of different behaviors. The contingency tables reveal large divergences between the ACSID-11 and other screening instruments concerning the classification of problematic specific Internet use based on the given cut-off values. ConclusionThe current work provides additional validation for the ACSID-11. Accordingly, this tool can be considered as reliable and valid for the simultaneous assessment of different Internet-use disorders: gaming disorder, online buying-shopping disorder, online pornography use disorder, social networks use disorder, and online gambling disorder. With a subsequent clinical validation of the scale and the proposed cut-off score, the ACSID-11 will be a thoroughly validated useful screening tool for clinical practice.

Chances and challenges of photon-counting CT in musculoskeletal imaging.

In musculoskeletal imaging, CT is used in a wide range of indications, either alone or in a synergistic approach with MRI. While MRI is the preferred modality for the assessment of soft tissues and bone marrow, CT excels in the imaging of high-contrast structures, such as mineralized tissue. Additionally, the introduction of dual-energy CT in clinical practice two decades ago opened the door for spectral imaging applications. Recently, the advent of photon-counting detectors (PCDs) has further advanced the potential of CT, at least in theory. Compared to conventional energy-integrating detectors (EIDs), PCDs providesuperior spatial resolution, reduced noise, and intrinsic spectral imaging capabilities. This review briefly describes the technical advantages of PCDs. For each technical feature, the corresponding applications in musculoskeletal imaging will be discussed, including high-spatial resolution imaging for the assessment of bone and crystal deposits, low-dose applications such as whole-body CT, as well as spectral imaging applications including the characterization of crystal deposits and imaging of metal hardware. Finally, we will highlight the potential of PCD-CT in emerging applications, underscoring the need for further preclinical and clinical validation to unleash its full clinical potential.

Advanced hemodynamics for prognostication in heart failure: the pursuit of the patient-specific tipping point.

Objective tools to define the optimal time for referral for advanced therapies and to help guide escalation and de-escalation of support can improve management decisions and outcomes for patients with advanced heart failure. The current parameters have variable prognostic potential depending on the patient population being studied and often have arbitrary thresholds. Here, a mathematical and physiological framework to define the patient-specific tipping point of myocardial energetics is defined. A novel hemodynamic parameter known as the myocardial performance score (MPS), a marker of power and efficiency, is introduced that allows for the objective assessment of the physiological tipping point. The performance of the MPS and other advanced hemodynamic parameters including aortic pulsatility index (API) and cardiac power output (CPO) in predicting myocardial energetics and the overall myocardial performance was evaluated using a validated computer simulation model of heart failure (Harvi) as well as a proof-of-concept clinical validation using a cohort of the Society for Cardiovascular Angiography and Interventions (SCAI) Stage C cardiogenic shock patients. Approximately 1010 discrete heart failure scenarios were modeled. API strongly correlated with the left ventricular coupling ratio (R2 = 0.81) and the strength of association became even stronger under loaded conditions where pulmonary capillary wedge pressure (PCWP) was >20 mmHg (R2 = 0.94). Under loaded conditions, there is a strong logarithmic relationship between MPS and mechanical efficiency (R2 = 0.93) with a precipitous rise in potential energy (PE) and drop in mechanical efficiency with an MPS <0.5. An MPS <0.5 was able to predict a CPO <0.6 W and coupling ratio of <0.7 with sensitivity (Sn) of 87%, specificity (Sp) of 91%, positive predictive value of 81%, and negative predictive value of 94%. In a cohort of 224 patients with SCAI Stage C shock requiring milrinone initiation, a baseline MPS score of <0.5 was associated with a 35% event rate of the composite endpoint of death, left ventricular assist device, or transplant at 30 days compared with 3% for those with an MPS >1 (p < 0.001). Patients who were able to augment their MPS to >1 after milrinone infusion had a lower event rate than those with insufficient reserve (40% vs. 16%, p = 0.01). The MPS, which defines the patient-specific power-to-efficiency ratio and is inversely proportional to PE, represents an objective assessment of the myocardial energetic state of a patient and can be used to define the physiological tipping point for patients with advanced heart failure.

Importance of the Posterior Plate in Three-Column Tibial Plateau Fractures: A Finite Element Analysis and Clinical Validation.

Dual-plate fixation was thought to be the gold standard for treating complicated bicondylar tibial plateau fractures, yet it was found to be hard to accommodate the posterior column in three-column fractures. Currently, column-specific fixation is becoming more and more recognized, but no comprehensive investigation has been performed to back it up. Therefore, the objective of this study was to validate the importance of posterior column fixation in the three-column tibial fractures by a finite element (FE) analysis and clinical study. In FE analysis, three models were developed: the longitudinal triple-plate group (LTPG), the oblique triple-plate group (OTPG), and the dual-plate group (DPG). Three loading scenarios were simulated. The distribution of the displacement and the equivalent von Mises stress (VMS) in each structure was calculated. The comparative measurements including the maximum posterior column collapse (MPCC), the maximum total displacement of the model (MTD), the maximum VMS of cortical posterior column (MPC-VMS), and the maximum VMS located on each group of plates and screws (MPS-VMS). The clinical study evaluated the indicators between the groups with or without the posterior plate, including operation time, blood loss volume, full-weight bearing period, Hospital for Special Surgery Knee Scoring system (HSS), Rasmussen score, and common postoperative complications. In the FE analysis, the MPCC, the MPC-VMS, and the MTD were detected in much lower amounts in LTPG and OTPG than in DPG. In comparison with DPG, the LTPG and OTPG had larger MPS-VMS. In the clinical study, 35 cases were included. In the triple-plate (14) and dual-plate (21) groups, the operation took 115.6 min and 100.5 min (p < 0.05), respectively. Blood loss in both groups was 287.0 mL and 206.6 mL (p < 0.05), and the full-weight bearing period was 14.5 weeks and 16.2 weeks (p < 0.05). At the final follow-up, the HSS score was 85.0 in the triple-plate group and 77.5 in the dual-plate (p < 0.05), the Rasmussen score was 24.1 and 21.6 (p < 0.05), there were two cases with reduction loss (9.5%) in the dual-plate group and one case of superficial incision infection found in the triple-plate group. The posterior implant was beneficial in optimizing the biomechanical stability and functional outcomes in the three-column tibial plateau fractures.