Screening Test Research Articles

Comparing ARR Versus Suppressed PRA as Screening Tests for Primary Aldosteronism.

In many practices, the screening for primary aldosteronism relies on a single-blood draw for plasma aldosterone concentration (PAC) and plasma renin activity (PRA) to establish an aldosterone-to-renin ratio (ARR). ARR levels vary between expert centers and repeated assays in the same individual, emphasizing the potential variability of this screening approach. A suppressed PRA to <1 ng/mL per h has been proposed as an alternative test to the ARR. We compared 2 potential screening approaches to identify probable primary aldosteronism (ARR≥30 or ARR≥20 versus PRA suppressed below 1 ng/mL per h) in a cohort of 94 829 paired PRA and PAC samples submitted by clinicians to evaluate the presence of primary aldosteronism. Of 94 829 patients, 20.3% tested positive based on ARR≥20 (95% CI, 20.0%-20.5%), 13.9% based on ARR≥30 (95% CI, 13.6%-14.1%), versus 45.9% based on suppressed PRA (<1 ng/mL per minute [95% CI, 45.5%-46.2%]). In the PRA group, a range of aldosterone levels was observed: 5.5% had PAC >15 ng/dL, 25.2% had PAC 5 to 15 ng/dL, and 15.2% had PAC <5 ng/dL, compared with 6%, 12.7%, and 1.6% in the ARR≥20 group and 4.7%, 8.5%, and 0.7% in the ARR≥30 group. In this cohort of individuals being screened for primary aldosteronism, substantially more individuals were identified using criteria focused on suppression of renin activity compared with using the aldosterone renin ratio as a screening tool.

Validation of Metallothionein Immunohistochemistry as a Highly Sensitive Screening Test for Wilson Disease

Wilson’s disease (WD) is a rare autosomal recessive condition with protean clinical manifestations that results from biallelic ATP7B mutations. However, non-destructive tissue tests to be applied clinically to tissue specimens are not widely available to effectively assess patients for possible WD. Previously, we showed that metallothionein (MTH) immunohistochemistry has a high sensitivity and specificity for WD diagnosis and, thus, represents a potentially powerful diagnostic tool that can be used in routine histologic sections. We sought to validate this finding in a large cohort of bona fide WD patients and to correlate metallothionein expression with other histologic features.We identified 91 cases of WD, which included 28 needle biopsies and 64 explants from 14 centers worldwide. Histologic features were evaluated, and a histopathological pattern was assigned to each case. All cases were evaluated with Masson trichrome and MTH immunohistochemistry (clone UC1MT, Abcam) using previously published technique. Liver tissues from chronic cholestatic diseases (n= 42) were used as controls.The median age of the cohort was 28.5 years. Out of 91 total cases, 83 were positive for MTH immunostain. In the controls, all 42 cases were negative for MTH immunostain. The sensitivity and specificity of MTH immunostain for WD were 91.20% and 100%, respectively.MTH immunohistochemistry is a highly sensitive and specific cost-effective screening tool for WD. It can be used for patients across age groups, varied histologic patterns, and fibrosis stages. This marker could prove to be a valuable tool in the evaluation of patients with possible WD.

The Next Frontier for Colorectal Cancer Screening: Blood-Based Tests.

Colorectal cancer is associated with substantial morbidity and mortality worldwide. Detection of early colorectal cancer is possible through approved screening tests but overall adherence is quite low. Implementation of effective noninvasive options could increase screening uptake and prevent a significant number of deaths. Noninvasive early cancer detection can potentially be achieved using a liquid biopsy. In this issue of Cancer Research, Cao and colleagues report on a novel multidimensional fragmentomics assay, named FRAGTECT, for colorectal cancer detection in circulating cell-free DNA with promising results. See related article by Cao et al., p. 3286.

Use of NIR in COVID-19 Screening: Proof of Principles for Future Application.

The COVID-19 pandemic that affected the world between 2019 and 2022 showed the need for new tools to be tested and developed to be applied in global emergencies. Although standard diagnostic tools exist, such as the reverse-transcription polymerase chain reaction (RT-PCR), these tools have shown severe limitations when mass application is required. Consequently, a pressing need remains to develop a rapid and efficient screening test to deliver reliable results. In this context, near-infrared spectroscopy (NIRS) is a fast and noninvasive vibrational technique capable of identifying the chemical composition of biofluids. This study aimed to develop a rapid NIRS testing methodology to identify individuals with COVID-19 through the spectral analysis of swabs collected from the oral cavity. Swab samples from 67 hospitalized individuals were analyzed using NIR equipment. The spectra were preprocessed, outliers were removed, and classification models were constructed using partial least-squares for discriminant analysis (PLS-DA). Two models were developed: one with all the original variables and another with a limited number of variables selected using ordered predictors selection (OPS-DA). The OPS-DA model effectively reduced the number of redundant variables, thereby improving the diagnostic metrics. The model achieved a sensitivity of 92%, a specificity of 100%, an accuracy of 95%, and an AUROC of 94% for positive samples. These preliminary results suggest that NIRS could be a potential tool for future clinical application. A fast methodology for COVID-19 detection would facilitate medical diagnoses and laboratory routines, helping to ensure appropriate treatment.

Diagnostic accuracy of the lactate stress test for detecting mitochondrial disorders: Systematic review and meta-analysis

Due to their variable phenotypes, mitochondrial disorders (MDs) can be difficult to diagnose. The absolute load lactate stress test (LSTA) and the relative load lactate stress test (LSTR) have been shown to be useful screening tools for the detection of MDs. In this study, we aimed to perform a meta-analysis to evaluate the diagnostic accuracy of these tests in detecting MDs. The study protocol was registered with PROSPERO (no. CRD42022331710). We performed a comprehensive search of PubMed, Web of Science and Scopus from January 10th, 2022 to July 27th, 2022 and included case-control and cohort diagnostic studies that targeted participants with MDs and used LSTA and/or LSTR as index tests. Two reviewers worked separately to compile information from selected articles. Risk of bias and applicability were assessed using the QUADAS-2 tool. Sensitivity and specificity, as well as diagnostic odds ratios (DORs) and area under the curve (AUC) were calculated using Meta-DiSc 2.0 and Stata software. The analysis included 14 studies with a total of 1064 participants, divided into six studies with 793 participants for LSTA and eight studies with 271 participants for LSTR. For LSTA the meta-analysis gave a pooled sensitivity of 0.67 (95 % CI 0.62, 0.72), a specificity of 0.93 (95 % CI 0.85, 0.97), DOR of 26.63 (95 % CI 10.99, 64.52), and AUC of 0.70 (95 % CI 0.66, 0.74). For LSTR, the pooled sensitivity was 0.52 (95 % CI 0.33, 0.70), specificity 0.94 (95 % CI 0.79, 0.99), DOR 18.14 (95 % CI 2.99, 109.85), and the AUC 0.80 (95 % CI 0.76, 0.83). LSTA and LSTR showed as screening tests moderate sensitivity and high specificity for MD diagnosis, particularly for LSTR. The choice of test may depend on the patient's individual aerobic capacity and motor skills and the availability of equipment.

S558 Test Performance and Lesion Characteristics in a Large Clinical Validation Study of a Blood-Based Screening Test for the Early Detection of Colorectal Cancer

S558 Test Performance and Lesion Characteristics in a Large Clinical Validation Study of a Blood-Based Screening Test for the Early Detection of Colorectal Cancer

S485 Projected Benefit and Cost-Effectiveness of Offering a Choice of Blood-Based Screening Versus Existing Screening Tests for Colorectal Cancer in Two Real-World Settings

S485 Projected Benefit and Cost-Effectiveness of Offering a Choice of Blood-Based Screening Versus Existing Screening Tests for Colorectal Cancer in Two Real-World Settings

Evaluation of nutritional status and malnutrition screening tests of elderly individuals living in nursing homes

Evaluation of nutritional status and malnutrition screening tests of elderly individuals living in nursing homes

Cushing syndrome in paediatric population: who and how to screen.

Cushing's syndrome (CS) is characterised by signs and symptoms resulting from excessive and prolonged exposure to exogenous glucocorticoids or endogenous hypercortisolism. In childhood, exogenous CS represents the main cause of CS due to the widespread therapeutic use of glucocorticoids, while endogenous CS is very rare and accounts for about 10% of CS cases. According to the origin of the hypercortisolism, the ACTH-dependent form due to pituitary ACTH-secreting tumours is the most common form of endogenous CS in paediatric age (about 75-80% of cases), following by adrenal causes (about 15-20% of cases) including adenoma, carcinoma (which has a peak of incidence in the first decade), bilateral adrenal hyperplasia or Carney complex, with a different distribution by age. Ectopic ACTH-secreting CS, genetic forms of pituitary adenomas are more uncommon. The insidious onset of hypercortisolism and the absence of salient early signs make the diagnosis of endogenous CS difficult. Facial changes, weight gain with simultaneous growth failure, prepubertal virilisation, or hypogonadism in adolescence represent some of the key features of CS. The diagnostic workup is essentially aimed at confirming hypercortisolism through screening tests whose diagnostic accuracy is not 100% and therefore the combination of more than two tests is mandatory to confirm the diagnosis of CS.

Mathematics Learning Model for Children with Dyscalculia through Special Intervention

This research aimed to formulate a model of mathematical learning difficulties for children with dyscalculia to help children with dyscalculia overcome mathematics problems at school. This research is important to carry out considering that dyscalculia is a serious problem experienced by many students throughout the world. The SDTA model was built by analogizing the STIR model to non-communicable diseases. In this study, of 1247 students who conducted a series of tests (screening tests), there were 121 students, or 9.7% were initially identified as having dyscalculia. Furthermore, observations were carried out and confirmation was carried out with parents and teachers so that 119 students tested positive for dyscalculia. The research results showed that after intervention through treatment by the teacher, dyscalculia students experienced a very drastic decrease, especially in the material on recognizing and ordering numbers. Likewise, the results of model simulations on multiplication operation material illustrated the decline in students with dyscalculia. Specifically for division operations, the treatment process took relatively longer. Therefore, the simulation results in the SDTA model reflected students who are identified as having dyscalculia, along with planned intervention/ treatment, students could pass through the mathematics learning phase successfully.

Screening for Helicobacter pylori to Prevent Gastric Cancer

Effects of screening for Helicobacter pylori on gastric cancer incidence and mortality are unknown. To evaluate the effects of an invitation to screen for H pylori on gastric cancer incidence and mortality. A pragmatic randomized clinical trial of residents aged 50 to 69 years in Changhua County, Taiwan, eligible for biennial fecal immunochemical tests (FIT) for colon cancer screening. Participants were randomized to either an invitation for H pylori stool antigen (HPSA) + FIT assessment or FIT alone. The study was conducted between January 1, 2014, and September 27, 2018. Final follow-up occurred December 31, 2020. Invitation for testing for H pylori stool antigen. The primary outcomes were gastric cancer incidence and gastric cancer mortality. All invited individuals were analyzed according to the groups to which they were randomized. Of 240 000 randomized adults (mean age, 58.1 years [SD, 5.6]; 46.8% female), 63 508 were invited for HPSA + FIT, and 88 995 were invited for FIT alone. Of the 240 000 randomized, 38 792 who were unreachable and 48 705 who did not receive an invitation were excluded. Of those invited, screening participation rates were 49.6% (31 497/63 508) for HPSA + FIT and 35.7% (31 777/88 995) for FIT alone. Among 12 142 participants (38.5%) with positive HPSA results, 8664 (71.4%) received antibiotic treatment, and eradication occurred in 91.9%. Gastric cancer incidence rates were 0.032% in the HPSA + FIT group and 0.037% in the FIT-alone group (mean difference, -0.005% [95% CI, -0.013% to 0.003%]; P = .23). Gastric cancer mortality rates were 0.015% in the HPSA + FIT group and 0.013% in the FIT-alone group (mean difference, 0.002% [95% CI, -0.004% to 0.007%]; P = .57). After adjusting for differences in screening participation, length of follow-up, and patient characteristics in post hoc analyses, an invitation for HPSA + FIT was associated with lower rates of gastric cancer (0.79 [95% CI, 0.63-0.98]) but not with gastric cancer mortality (1.02 [95% CI, 0.73-1.40]), compared with FIT alone. Among participants who received antibiotics, the most common adverse effects were abdominal pain or diarrhea (2.1%) and dyspepsia or poor appetite (0.8%). Among residents of Taiwan, an invitation to test for HPSA combined with FIT did not reduce rates of gastric cancer or gastric cancer mortality, compared with an invitation for FIT alone. However, when differences in screening participation and length of follow-up were accounted for, gastric cancer incidence, but not gastric cancer mortality, was lower in the HSPA + FIT group, compared with FIT alone. ClinicalTrials.gov Identifier: NCT01741363.

Keun Lee (October 10, 1942 – May 14, 2024): A pioneering pediatrician in the field of developmental screening tests in Korea and a beloved teacher at Ewha Womans University College of Medicine

Keun Lee (October 10, 1942 – May 14, 2024): A pioneering pediatrician in the field of developmental screening tests in Korea and a beloved teacher at Ewha Womans University College of Medicine

The Accuracy and Efficiency of the Speech Language Early Literacy Screening Checklist

Objectives: This study aimed to develop the “Speech Language Early Literacy Screening Checklist” in order to identify speech, language, and early literacy difficulties in children aged 5-6 years before entering elementary school. This study examined the reliability, validity, sensitivity, specificity, positive predictive value, and negative predictive value to verify the accuracy and efficiency of the checklist as a screening tool.Methods: Out of the 2,880 children who participated in the initial screening test, 155 underwent diagnostic deep tests. A total of 110 children who exhibited difficulties in language, speech, and early literacy areas were classified as the high-risk group, while those who demonstrated appropriate development in all areas were classified as the general group.Results: The Cronbach’s α value for all checklist items was .884. The content validity index rated by six language development experts was 0.70 or higher for all 36 items, with an average content validity score of 0.91. Clinical validity was confirmed through the total score differences between the general and high-risk groups classified by the diagnostic deep tests. The receiver operating characteristic (ROC) curve results for the screening checklist showed an area under the curve (AUC) of 0.858, sensitivity of 84.4%, and specificity of 76.4%. The positive predictive value (PPV) calculated from the cut-off score was 92.3%.Conclusion: The “Speech Language Early Literacy Screening Checklist” developed to identify children at high risk of language development delays before school entry has shown appropriate reliability, validity, and classification accuracy. This study suggests that the implementation of this checklist will contribute to preventing school failure by effectively identifying at-risk children aged 5-6.

Where do we stand with screening for colorectal cancer and advanced adenoma based on serum protein biomarkers? A systematic review.

Colorectal cancer (CRC) screening has been proven to reduce both mortality and the incidence of this disease. Most CRC screening programs are based on fecal immunochemical tests (FITs), which have a low participation rate. Searching for blood protein biomarkers can lead to the development of a more accepted screening test. The aim of this systematic review was to compare the diagnostic potential of the most promising serum protein biomarkers. A systematic review based on PRISMA guidelines was conducted in the PubMed and Web of Science databases between January 2010 and December 2023. Studies assessing blood protein biomarkers for CRC screening were included. The sensitivity, specificity, and area under the ROC curve of each biomarker were collected. Among 4685 screened studies, 94 were considered for analysis. Most of them were case-control studies, leading to an overestimation of the performance of candidate biomarkers. The performance of no protein biomarker or combination of biomarkers appears to match that of the FIT. Studies with a suitable design and population, testing new assay techniques, or based on algorithms combining FIT with serum tests are needed.

Frequency of clinical signs in patients with Cushing's syndrome and mild autonomous cortisol secretion: overlap is common.

Cushing's syndrome (CS) can be difficult to diagnose. A timely diagnosis, however, is the cornerstone for targeted treatment, to reduce morbidity and mortality. One reason for the difficulties to identify early on patients with CS might be the presence of a mild phenotype. The aim of the study was to classify the phenotypic landscape of CS. We studied patients with overt CS and mild autonomous cortisol secretion (MACS). The study was part of the German Cushing's registry. Patients were prospectively included at time of diagnosis and the number of comorbidities and clinical signs and symptoms were assessed in a standardized fashion. One hundred twenty-nine patients with CS (pituitary CS, n = 85, adrenal CS, n = 32, ectopic CS, n = 12, respectively) and 48 patients with MACS were included. Patients with clinical signs and/or comorbidities typical for CS and at least 2 pathological screening tests were classified as having CS. Patients with a 1 mg low-dose-dexamethasone-suppression test above 1.8 µg/dL without being clinically overt CS were classified as having MACS. On average, patients with CS had 2 comorbidities (range 1-3) at time of diagnosis (pituitary CS: 2 [1-3], adrenal CS: 3 [2-4], ectopic CS: 3 [2-4]). Patients with MACS, however, had 3 comorbidities (range 2-3). Hypertension was the most common comorbidity in all subtypes of CS (78%-92%) and in patients with MACS (87%). Of a total of 11 clinical signs, patients with CS had on average 5 with 28% of patients having between 0 and 3 clinical signs, 50% 4-7 signs, and 22% more than 7 clinical signs. Patients with MACS had on average 2 clinical signs (range 1-3) at time of diagnosis. The phenotypic landscape of CS is quite variable. The frequency of comorbidities is similar between patients with CS and MACS. A relevant number of patients with overt CS have just a few clinical signs. There is also an overlap in frequency of symptoms and clinical signs between patients with CS and MACS. According to the current guidelines, 96% of our patients with MACS fall into the category "consideration of adrenalectomy". This should be kept in mind when making treatment decisions in the latter group of patients.

Polyenylphosphatidylcholine alleviates cardiorenal fibrosis, injury and dysfunction in spontaneously hypertensive rats by regulating Plpp3 signaling.

Polyenylphosphatidylcholine (PPC), a significant therapeutic agent for liver repair, exhibits potent antioxidant and anti-inflammatory properties. Nonetheless, its impact on hypertension and hypertensive vascular diseases requires clarification. Our objective was to elucidate the protective role and mechanism of PPC in a spontaneously hypertensive rat model. Male WKY and SHRs were randomly assigned to four groups: WKY control, SHRs control, SHRs treated with Telmisartan (SHR-TS), and SHRs treated with PPC (SHR-PPC). Blood pressure was monitored biweekly during the treatment. Histological analyses assessed aortic vascular remodeling and cardiac and renal injuries. RNA-seq was performed on vascular smooth muscle cells (VSMCs) isolated from WKY or SHRs, and protein levels of target genes were quantified using Western blotting. In a dose-dependent screening test, we confirmed that PPC (200 mg/kg/day) effectively reduced blood pressure in SHRs. Treatment with PPC also mitigated cardiac and renal injury in SHRs by attenuating hypertrophy and fibrosis. Compared to WKY rats, SHRs exhibited increased intima thickness, reduced vascular tone, and heightened aortic fibrosis; however, PPC treatment significantly reversed vascular remodeling. Analysis of RNA-seq data revealed that downregulated genes were enriched in inflammation and oxidative stress pathways based on GO and KEGG enrichment analyses. PPC markedly inhibited genes such as Rela, Relb, Nfkb2, and others involved in the NF-κB pathway. Given PPC's influence on glycerophospholipid synthesis and metabolism, and its role in NF-κB-mediated transcription affecting oxidative stress and inflammation, changes in the PLAs, PLPs, and PLPPs families were analyzed in PPC-treated VSMCs. Among these, PPC notably inhibited Plpp3. Importantly, overexpression of Plpp3 significantly reversed the protective effects of PPC on hypertension-related cardiac and renal injuries, vascular fibrosis, remodeling, and tension. We identified a new protective role for PPC in mitigating cardiac and renal injuries associated with hypertension, as well as in preventing aortic fibrosis and remodeling. Targeting the NF-κB/Plpp3 pathway may offer a promising therapeutic strategy for treating vascular diseases related to hypertension.

Preliminary Study to Assess the Antioxidant and Antibacterial Activity of Extracts from the Leaves of Morelia Senegalensis (A Rich)

frican populations rely heavily on traditional medicine, which uses plants to treat human and animal diseases. However, scientific validation of this empirical knowledge concerning the efficacy, toxicity and dosage of the proposed treatments is urgently needed. The aim of this study was to evaluate the antioxidant and antibacterial activity of Morelia senegalensis leaf extracts on the 2,2-diphenyl-1-picrylhydrawyl (DPPH) radical and the (2,2’-azino-bis-(3-ethylbenzothiazoline-6-sulfonic) acid) ABTS cation radical and on four reference bacterial strains (E. coli 25922, E. coli 35218, E. faecalis 29212 and S. aureus 29213) using protocols already described in the literature. The phytochemical screening test revealed the presence of flavonoids, alkaloids, tannins, saponins, reducing compounds and sterols in Morelia senegalensis leaves. All the extracts showed antioxidant activity to varying degrees. The most active ethyl acetate (AE) extract had half-maximum inhibition concentration (IC50 )of 0.33 and 0.62 mg/mL for the ABTS and DPPH tests respectively, followed by DCM and EB extracts with IC50 of 0.86 and 0.88 mg/mL for the ABTS test respectively, while the vitamin C used as a reference was more active with IC50 of 0.04 and 0.06 mg/mL. Antibacterial activity showed inhibition diameters ranging from 7 to 16 mm depending on the concentration and strain considered. The ethyl acetate fraction was the most active on S aureus 29213 with an inhibition diameter of 16 mm at 50 mg/mL. These interesting results were confirmed by the Minimal Inhibitory Concentration inhibitory (MIC) and Minimal Bacterial Concentration (MBC) studies, which showed that all the extracts had a bactericidal effect on all the studied strains. Morelia senegalensis plant has shown promising preliminary results in the treatment of bacterial infections. Further studies are needed to isolate and characterize the secondary metabolites contained in the leaves of this plant.

Assessment and Laboratory Screening Test of Abnormal Blood Creatinine Level among Hypertensive Patient Attending at Some Selected Hospitals in Mogadishu Somalia

Assessment and Laboratory Screening Test of Abnormal Blood Creatinine Level among Hypertensive Patient Attending at Some Selected Hospitals in Mogadishu Somalia

Null projection screen test for aerodynamic surfaces on wind turbine blades

This work proposes a novel method, to our knowledge, to qualitatively test aerodynamic surfaces by projecting a null screen. The main idea is, by using ray tracing equations in a model with two pinhole systems, to map an ordered predefined array of fringes formed by points on the detection plane, defined as a CMOS sensor, to the projection plane of a commercial projector, passing through the surface under test whose geometry must be known in advance. Once the coordinates on the projection plane are calculated, the pattern is projected onto the aerodynamic surface. The proposed predefined array will be observed by the camera if the surface and the alignment of the optical systems are perfect; otherwise, a distorted array will be detected, indicating misalignment or that the surface has defects that can be observed qualitatively. The mathematical expressions found to perform the direct and inverse ray tracing in 3D are applied to design a null test by projection on a reference plane and on an aerodynamic surface based on the NACA 0012 airfoil.

Survival of lung cancer patients according to screening eligibility using Korean Lung Cancer Registry 2014–2016

This study assessed survival for lung cancer patients meeting criteria for the National Lung Cancer Screening Program in Korea launched in 2019 and updated guideline reported by the US Preventive Service Task Force (USPSTF). We assessed all-cause mortality based on the Korean Lung Cancer Registry (KLCR), including lung cancer patients diagnosed in 2014–2016. We compared survival among lung cancer patients eligible for extended USPSTF criteria (age 50–80 years and ≥ 20 pack-years) and those meeting current criteria (age 54–74 years and ≥ 30 pack-years, current or within the past 15 years). The nearest neighbour propensity-score matching was performed to generate a matched set. Kaplan–Meier curves were generated to compare survival among groups; differences in survival were analyzed using the stratified log-rank test. The mortality risk was estimated based on a Cox proportional hazards regression model and the robust standard error was calculated. Of 8110 patients, 37.4% and 24.3% met the extended USPSTF eligibility criteria and National Lung Cancer Screening Program (NLCSP) criteria, respectively. Overall mortality risk was not significantly different between the extended younger age group and the NLCSP group (hazard ratio [HR] [95% confidence interval (CI)]: 0.78 [0.59–1.02]). The extended older age group had a significantly higher mortality risk (HR [95% CI]: 1.41 [1.26–1.58]). Mortality risk was not significantly different between patients who smoked 20–29 pack-years and those who smoked ≥ 30 pack-years (HR [95% CI]: 0.90 [0.79–1.03]). Lung cancer patients aged 50–53 years and those with a 20–29 pack-years smoking history exhibited similar mortality risk to individuals meeting current criteria, while patients aged 75–80 years were at a higher risk of death. Although we verified similar or higher mortality risks in extended subgroups, a careful assessment of the benefits and harms of the screening tests is necessary when contemplating the extension of criteria.