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Diagnostic and Predictive Value of Circulating and Exosomal microRNAs in Ferroptosis-Associated Neurological Conditions: A Systematic Review and Meta-analysis.

Circulating microRNAs (miRNAs) have emerged as potential non-invasive markers for intracranial pathology, yet their diagnostic accuracy and relationship with ferroptosis-mediated neuronal damage remain poorly defined. The primary objective of this study was to evaluate the diagnostic and predictive potential of circulating and exosomal miRNAs across ferroptosis-associated neurological conditions and to explore their associations with ferroptosis-related pathways. Following PRISMA-DTA guidelines, a systematic literature search was conducted across PubMed, Scopus, Cochrane, and ScienceDirect, identifying 205 records. After screening for human clinical cohort validation, 7 studies were included in the qualitative synthesis and 5 in the quantitative meta-analysis. Pooled Area-under-the-Curve (AUC) was calculated using a random-effects inverse-variance model, while prognostic correlation coefficients (r) were synthesized using Fisher's Z-transformation. Methodological quality was assessed via QUADAS-2. Analysis of 7 clinical cohorts provided heterogeneous evidence on the diagnostic and prognostic potential of miRNAs. Random-effects pooling of the two eligible diagnostic AUC estimates yielded an exploratory pooled AUC of 0.87 (95% CI, 0.79-0.94; I2 .90%). Prognostic synthesis of Group 2 identified an exploratory association between miRNA levels and clinical severity scales (exploratory pooled correlation coefficient of 0.67 (95% CI: 0.56-0.76; I2 .714.4%). Selected miRNAs were mapped to ferroptosis-associated regulators, including SLC7A11, ABCB8, and SLC40A1. Exosomal miRNAs hold potential to indicate disease-associated molecular information, although comparative clinical evidence remains yet to be explored. Circulating and exosomal miRNAs show promising diagnostic and prognostic potential across selected neurological conditions. These findings highlight a potential mechanistic association between miRNA expression and ferroptosis-mediated neuronal injury.

Humans↗

Seeking and applying diagnostic information in a health care setting.

Many studies have shown that people have difficulty judging the diagnostic value of conditional probability information with respect to one or more hypotheses. The present research addressed two aspects of performing the diagnostic task in a health care decision: (a) recognition of the information's importance, and (b) correct usage of that information. In experiment 1, health care providers, who are trained in, and regularly exposed, to conditional probabilities imparting diagnostic information, exhibited at least a rudimentary recognition of the need for this information in assessing diagnosticity. Experiment 2 indicated that health care and layperson subjects had difficulty in actually applying the information, however. This difficulty prompts a need for judgment aids and caution in using diagnostic information.

Bayes Theorem↗

Usefulness of diagnostic tests for biliary obstruction.

We studied the value of tests commonly used in diagnosing obstructive jaundice in 188 patients operated on for biliary obstruction. Ultrasonography had a diagnostic accuracy of 87 percent for gallbladder stones, 82 percent for dilated ducts, and 80 percent for pancreatic masses. Computed tomography was 93 percent accurate in diagnosing dilated ducts, and 93 percent accurate in diagnosing a pancreatic mass. Intravenous cholangiography gave useful information in only 4 of 21 patients. Among 45 patients, endoscopic retrograde cholangiopancreatography was technically successful in 91 percent and gave accurate diagnostic information in 86 percent and partially diagnostic information in 7 percent; it detected all cases of common duct stones and had a 91 percent sensitivity for detecting pancreatic cancer. Among 75 patients, transhepatic cholangiography was technically successful in 95 percent and provided accurate diagnostic information in 90 percent and partially diagnostic information in 3 percent; it detected all cases of common duct stones and 95 percent of cases of benign strictures. With persistent jaundice, ultrasonography should be the first test because it is less costly than computed tomography and provides similar information. If more information is needed, transhepatic cholangiography and endoscopic retrograde cholangiopancreatography are equally accurate; transhepatic cholangiography more often opacifies the proximal biliary tree and endoscopic retrograde cholangiopancreatography provides direct access to the ampulla of Vater and the pancreatic duct.

Bile Duct Diseases↗

Stratified diagnostic approach to fine needle aspiration of the breast.

The clinical value of fine needle aspiration (FNA) of the breast is enhanced by incorporating into the cytologic diagnosis explicit comments on the level of diagnostic certainty. This stratification of diagnostic certainty is based predominantly on the cytologic features but occasionally also takes into consideration the clinical situation. Strong clinical and mammographic suspicion of mammary carcinoma associated with FNA, diagnostic of typical, intermediate to high-grade mammary carcinoma, warrants proceeding to definitive therapy without further diagnostic studies. False-positive results are virtually eliminated by placing cases with any uncertainty into a "probable" category, which does not support definitive therapy. In addition, oversimplified "benign versus malignant" approaches to FNA diagnoses ignore the heterogeneity of breast masses, with in situ and low-grade carcinomas warranting special clinical management and usually being placed in the "probable" category. Thus, malignant diagnoses are stratified into "definite" and "probable," with only the former supporting definitive therapy. Within our recent series of 1,005 FNAs of the breast, we were able to confirm the diagnosis in all 62 patients with a "definite" carcinoma diagnosis, and only 3 of 25 "probable" cancer diagnoses were benign at tissue biopsy. Thus, false-positive results were successfully avoided in the "definite" category. Furthermore, a much greater incidence of unusual and good prognosis tumor types were identified by the "probable" category. If the clinical setting is relatively suspicious only, a definitive diagnosis of cancer by FNA is rare and not necessary because the clinical question to be addressed is only whether to biopsy. This approach to FNA diagnosis, unlike the oversimplified "benign versus malignant" scheme, provides an approach that is more likely to result in optimal therapy for breast neoplasms, with low-grade or in situ carcinomas requiring special clinical management since these types of cancers are found predominantly in the "probably malignant" category. It also provides additional security against false-positive diagnoses by incorporating clinical level of certainty statements into FNA diagnostic categories, which more closely reflect the diversity and inherent complexity in the appropriate diagnosis and therapy of mammary carcinomas.

Biopsy, Needle↗

Optimizing REM latency as a diagnostic test for depression using receiver operating characteristic analysis and information theory.

New diagnostic techniques must be evaluated for their intrinsic accuracy and for their applicability to particular patient groups in specific clinical settings. Using receiver operating characteristic (ROC) analysis and concepts from information theory, we have developed a new mathematical and graphical method that can evaluate, compare, and optimize the performance of diagnostic tests for any value of disorder prevalence. Our analytic method is appropriate to any test that sorts disordered from nondisordered subjects using a continuous or nonbinary diagnostic variable; its characterization of the fundamental properties of such tests thus has important implications for the evaluation and optimization of diagnostic modalities used by clinicians in all medical specialties. We demonstrate our method using published data from five studies that used sleep architecture as a "biological marker" for depression. Our analysis confirms that REM latency is comparable to the dexamethasone suppression test in its ability to discriminate depressed from control subjects. For each of the five studies, we show how optimal REM latency cut-off times may be selected so that diagnostic information yield is maximized, and we compare the ability of each study to detect depressed subjects in populations where the prevalence of affective disorder can be specified.

Adult↗

Diagnostic sensitivity of fasting and postprandial serum bile acids determined by different methods.

The diagnostic sensitivities of serum bile acids determined by three different methods in the fasting and in the postprandial state were compared in 43 patients with cirrhosis of the liver. When a method with high analytical sensitivity (capillary gas-liquid chromatography, GLC, or radioimmunoassay, RIA) was used, the serum concentrations of bile acids exhibited similar diagnostic sensitivities in the fasting state (GLC, 98%; RIA, 93%) and in the postprandial state (GLC, 95%; RIA, 93%). By contrast, when an enzymatic method with limited analytical sensitivity was employed, the diagnostic sensitivity of fasting serum bile acids was lower (79%) than that of postprandial serum bile acids (93%). The measurement of individual serum bile acids by GLC did not add any further diagnostic information. The results of this study demonstrate that the diagnostic sensitivity of serum bile acids strongly depends on the analytical method used.

Adult↗

pH of ascitic fluid: diagnostic and prognostic value in cirrhotic and noncirrhotic patients.

The pH measurements of 185 samples of ascitic fluid in 169 cirrhotic and 16 noncirrhotic patients were analyzed to assess their diagnostic and prognostic value. The 169 cirrhotic patients were divided into four groups: sterile ascites (group 1), spontaneous bacterial peritonitis (group 2), probable spontaneous bacterial peritonitis (group 3), and bacterascites (group 4). Mean ascitic fluid pH values were lower (p less than 0.001) in patients of groups 2 (7.24 +/- 0.17) and 3 (7.34 +/- 0.11) than in patients of groups 1 (7.44 +/- 0.06) and 4 (7.45 +/- 0.08), but there was an important overlap between these groups. Mean arterial-ascitic fluid pH gradient values were higher (p less than 0.001) in patients of groups 2 (0.21 +/- 0.16) and 3 (0.10 +/- 0.13) than in patients of groups 1 (0.02 +/- 0.05) and 4 (0.02 +/- 0.05). This gradient had a better discriminant power than ascitic fluid pH alone. Sensitivity, specificity, positive and negative predictive value, and diagnostic accuracy for the diagnosis of certain or probable spontaneous bacterial peritonitis were, respectively, 47%, 99%, 88%, 89%, and 89% for ascitic fluid pH values less than 7.32; 66%, 99%, 91%, 93%, and 92% for arterial-ascitic fluid pH gradient values greater than 0.10; and 97%, 96%, 86%, 99%, and 96% for polymorphonuclear cell count greater than 75/microliter. Ascitic fluid pH values appeared to have a high prognostic value, as 6 of 7 cirrhotic patients with ascitic fluid pH values less than 7.15 died rapidly. Low ascitic fluid pH values were found in patients with malignant and pancreatic ascites and tuberculous peritonitis but not in patients with cardiac ascites. We conclude that in cirrhotic patients with certain or probable spontaneous bacterial peritonitis (a) arterial-ascitic fluid pH gradient measurements had a slightly higher diagnostic value than ascitic fluid pH measurements but a slightly lower diagnostic value than polymorphonuclear cell count and (b) ascitic fluid pH measurements had a high prognostic value. In noncirrhotic patients, ascitic fluid pH and arterial-ascitic fluid pH gradient measurements had a poor diagnostic value.

Adolescent↗

Classification of diagnostic tests.

A method is described for classifying diagnostic tests. It is valid for the large subgroup of tests for which the measured diagnostic variable has a normal distribution for the affected and non-affected individuals. It is based on placing each diagnostic test as a point on a two-dimensional graph, called a separation-asymmetry (SA) diagram, whose x-axis is the separation between the two normal distributions and whose y-axis is the logarithm of the ratio of their standard deviations. The SA diagram is partitioned into functional regions by curves of constant performance, as measured by the percent overlap between the two normal distributions. The concept of 'eccentricity' in a diagnostic test is defined, and the relationship between eccentricity and test validity is discussed. This quantity is also incorporated into SA diagrams, thus allowing a clinician to determine, by inspection, if a given diagnostic test positioned on an SA diagram is valid for clinical use. The logic engine used for calculating iso-performance curves is given, as well as the computer programs which utilize it. Possible ways of using this classification scheme are suggested.

Algorithms↗

Predictive value: a model for dentists to evaluate the accuracy of diagnostic tests for temporomandibular disorders as applied to a TMJ scale.

The predictive value model for assessing the accuracy of diagnostic test results in the individual patient with a temporomandibular disorder is described. The use of predictive values to help the clinician ascertain the degree of confidence to be placed in diagnostic test results is illustrated. The predictive value model is used to study the accuracy of the TMJ Scale as a diagnostic tool. For all base rates between 0% and 100%, the predictive values of the TMJ Scale result in a gain in accuracy in confirming or excluding a diagnosis of a temporomandibular disorder. The TMJ Scale provides the dentist with improved accuracy of diagnostic decisions regarding the presence of temporomandibular disorders throughout the entire range of base rates found in clinical practice. Application of the predictive value model helps the dentist avoid serious diagnostic errors that could place both the patient and dentist at unnecessary risk.

Humans↗

Issues of validity in the Diagnostic Interview Schedule.

The Diagnostic Interview Schedule, the chief instrument in contemporary studies in psychiatric epidemiology, enhances the reliability of psychiatric diagnosis and enables lay interviewers to closely reproduce psychiatric interviews. However, despite frequent references in the literature to the validity of the Diagnostic Interview Schedule, most studies fundamentally represent variations of reliability paradigms to the neglect of criterion-related validity. Mistaken assertions of validity persist in the psychometric language used to describe the Diagnostic Interview Schedule. This article examines the basis for claims and counterclaims of validity in accordance with standard psychometric definition, and identifies sources of erroneous reasoning in attempts to infer validity from reliability. The article presents a general framework organizing the process of diagnostic validation and discusses strategies for research seeking to validate psychiatric diagnoses achieved through the Diagnostic Interview Schedule.

Humans↗

Reliability and validity studies of the WHO--Composite International Diagnostic Interview (CIDI): a critical review.

This paper reviews reliability and validity studies of the WHO - Composite International Diagnostic Interview (CIDI). The CIDI is a comprehensive and fully standardized diagnostic interview designed for assessing mental disorders according to the definitions of the Diagnostic Criteria for Research of ICD-10 and DSM-III-R. The instrument contains 276 symptom questions many of which are coupled with probe questions to evaluate symptom severity, as well as questions for assessing help-seeking behavior, psychosocial impairments, and other episode-related questions. Although primarily intended for use in epidemiological studies of mental disorders, it is also being used extensively for clinical and other research purposes. The review documents the wide spread use of the instrument and discusses several test-retest and interrater reliability studies of the CIDI. Both types of studies have confirmed good to excellent Kappa coefficients for most diagnostic sections. In international multicenter studies as well as several smaller center studies the CIDI was judged to be acceptable for most subjects and was found to be appropriate for use in different kinds of settings and countries. There is however still a need for reliability studies in general population samples, the area the CIDI was primary intended for. Only a few selected aspects of validity have been examined so far, mostly in smaller selected clinical samples. The need for further procedural validity studies of the CIDI with clinical instruments such as the SCAN as well as cognitive validation studies is emphasized. The latter should focus on specific aspects, such as the use of standardized questions in the elderly, cognitive probes to improve recall of episodes and their timing, as well as the role of order effects in the presentation of diagnostic sections.

Cross-Cultural Comparison↗

Diagnostic imaging assessment of experimental intraoral "folded film".

"Folded film" is an experimental technique of film preparation that provides diagnostic imaging of intraoral structures with one-half the radiation required to produce conventional images. In this study, folded film periapical images were compared with similar conventional D- and E-speed film images with the use of 12 criteria for diagnostic visualization. Nineteen examiners judged folded films to be slightly less diagnostic than D-speed film images and somewhat more diagnostic than E-speed films. All systems were judged adequate for diagnostic visualization of bone and teeth.

Radiographic Image Enhancement↗

Evaluation of a Diagnostic Encyclopedia Workstation for ovarian pathology.

The Diagnostic Encyclopedia Workstation (DEW) is a computer system that provides completely integrated pictorial and textual information as reference knowledge in the field of ovarian pathology. The textual component comprises information per diagnosis such as descriptions of macroscopic and microscopic images, clinical signs, and prognosis. In addition, the system offers lists of differential diagnoses and criteria to differentiate among lists of differential diagnoses and criteria to differentiate among them. The present study evaluates to what extent the system influences the diagnostic process in efficiency and outcome. Therefore, two groups of six pathologists each, covering a wide spectrum of experience in ovarian pathology, participated in the evaluation of the DEW. The quality of the resulting diagnoses was statistically analyzed with the Wilcoxon rank sum test with respect to five different viewpoints: classification, morphology, clinical consequences, duration of diagnostic process, and consensus among the participants. The results are discussed and it is concluded that classification and morphology showed better results when books were used. The evaluation experiment was, however, very rigid and negatively biased with respect to the DEW system. Positive aspects of the encyclopedia are the easy access to diagnostic and differential diagnostic information and the large set of illustrations. Insight is acquired with respect to existing bottlenecks and how they may be overcome.

Computer Systems↗

Diagnostic usefulness of nasal biopsy in Wegener's granulomatosis.

Wegener's granulomatosis (WG) frequently involves the upper respiratory tract, and nasal mucosal biopsy is often initially used to establish the diagnosis. To evaluate the diagnostic efficacy of nasal biopsy in WG, we reviewed the pathologic features of 30 such biopsy specimens from 17 patients with well-documented WG. Active vasculitis (granulomatous or nongranulomatous) was identified in seven of the patients (41%). The presence of extravascular foci of necrosis in lung biopsy samples has recently received attention as a characteristic feature of WG. Similar foci were found in the nasal samples from six of our patients, although vasculitis was absent in the samples from two of them. If extravascular foci of necrosis are regarded as characteristic or even diagnostic of WG, two additional patients in our series could be regarded as having had diagnostic nasal biopsies (nine of 17 patients). Nasal biopsy could thus be considered as diagnostic in 53% of the patients. Samples larger than 5 mm in greatest dimension were more likely to contain diagnostic features than were smaller samples (P = 0.002).

Adolescent↗

Diagnostic criteria of limited adenocarcinoma of the prostate on needle biopsy.

Over a period of 25 weeks 434 needle biopsy specimens of the prostate were sent to the author for consultation because of diagnostic concerns. The final diagnoses were cancer (69%), benign (13%), atypical but not diagnostic (10%), high grade prostatic intraepithelial neoplasia (PIN) (5%), and miscellaneous (3%). The most common benign entities mimicking cancer were atrophy (29 specimens) and adenosis (19 specimens). The 300 cancer specimens were analyzed further. Architecturally, the presence of small glands between larger benign glands was the most common pattern seen in 80% of carcinomas; haphazard growth patterns, single cells, and cribriform glands were seen less frequently. The following diagnostic features were helpful: nuclear enlargement (77% of specimens); prominent nucleoli (76%); pink acellular intraluminal secretions (53%); amphophilic cytoplasm (39%); blue-tinged mucinous secretions (34%); crystalloids (25%); PIN (13%); mitotic figures (11%); and perineural invasion (3%). The mean and median numbers of malignant glands in this series were 31 and 20, respectively (range, two to 300). Tumors with a Gleason score lower than 6 caused greater diagnostic problems for referring physicians because these tumors had a greater number of malignant glands, yet were still sent in for consultation (P = .0018). Gleason score was positively correlated with prominent nucleoli and amphophilic cytoplasm and inversely correlated with the presence of crystalloids. Prominent nucleoli, which often are quoted as being essential for the diagnosis of prostate cancer, were not seen in 24% of the specimens and seen only rarely in another 25%. The diagnosis of prostate cancer is based on a constellation of features. Even in this series with a limited number of malignant glands, 85% of specimens contained three or more of the above-listed diagnostic features in addition to architectural atypia.

Adenocarcinoma↗

Photoacoustic diagnostics of fast photochemical and photobiological processes. Analysis of inverse problem solution.

Photoacoustic (PA) diagnostics is a time-resolved experimental technique that measures transient photoinduced volume changes on the nano- and microsecond time-scales. The technique has been used to study the energetics and dynamics of chemical and biochemical reactions initiated by absorption of light. The dynamics of the volume changes and associated relaxation processes can be restored from PA-waveforms by solving an ill-posed problem of deconvolution. For the systems with known relaxation kinetics scheme this problem is usually solved by an iterative approximation algorithm. In complex photoactive systems (e.g. photosynthetic samples), where information about kinetics of fast photoinduced volume changes is not available, an algorithm of direct deconvolution must be used. The implementation of one of the linear deconvolution algorithms (Tikhonov's alpha-regularization) for the PA-diagnostics is therefore considered. The problem of the optimal choice of experimental set-up, and restoration algorithm is analyzed by a numerical simulation. It is shown that the quality of PA-diagnostic experiment is mainly determined by a transfer function converting the relaxation spectrum to the spectrum of output electric signal. The analytical expressions to calculate this function (so called PA-filter) are presented. The performance of two widely used schemes of PA-diagnostics are then directly compared. The time-resolution of the PA-diagnostics in analysis of simultaneous bi-exponential decay is evaluated, and the relationship between the resolving power and parameters of the experimental set-up (signal-to-noise ratio, sampling rate, shape of the PA-filter) is found. The advantage of front face irradiation scheme with piezopolymer film detector for time-resolved measurements is demonstrated.

Journal Article↗

The false-positive rate of uncontrolled diagnostic blocks of the lumbar zygapophysial joints.

One hundred and seventy-six consecutive patients with chronic low back pain and no history of previous lumbar surgery were studied to determine the false-positive rate of single diagnostic blocks of the lumbar zygapophysial joints. All patients underwent diagnostic blocks using lignocaine. Those patients who obtained definite or complete relief from these blocks subsequently underwent confirmatory blocks using bupivacaine. Eighty-three patients (47%) had a definite or greater response to the initial, lignocaine injection at one or more levels but only 26 (15%) had a 50% or greater response to a confirmatory injection of 0.5% bupivacaine. Using the response to confirmatory blocks as the criterion standard, the false-positive rate of uncontrolled diagnostic blocks was 38% and the positive predictive value of these blocks was only 31%. Because the positive predictive value of a test is lower when the pre-test probability (prevalence) is low, and because the prevalence of lumbar zygapophysial joint pain is likely to be less than 50%, uncontrolled diagnostic blocks will always be associated with an unacceptably low positive predictive value. These features render uncontrolled diagnostic blocks unreliable for the diagnosis of lumbar zygapophysial joint pain not only in epidemiologic studies but also in any given patient.

Adult↗

Diagnostic entropy as a function of therapeutic benefit/risk ratio.

Current clinical practice is based upon 'out stubborn quest for diagnostic certainty' which in turn is considered as one of the major reasons for ever-increasing health costs. We linked a treatment-threshold concept with classic information theory to show that measurable clinical variables, such as benefit and risk of available treatments, can be used to calculate the acceptable levels of diagnostic uncertainties associated with a particular clinical situation. Our analysis shows that practising physicians should aim for diagnostic certainty only when the benefit of treatment is equal to its associated risk. In all other cases, decisions about treatment do not have to rely on maximum diagnostic certainty. Determination of acceptable levels of diagnostic uncertainty according to the concepts outlined here should lead to improvement of clinical practice and decrease healthcare costs.

Appendicitis↗