Diagnostic Issues Research Articles

Utility of the Serum Protein Electrophoresis in the Opportunistic Screening for the Deficiency of Alpha-1 Antitrypsin.

A deficiency in alpha-1 antitrypsin (AAT1) is a rare disorder that represents a significant health threat and early diagnostic priority issue. We investigated the usefulness of the serum protein electrophoresis (SPE) as an opportunistic screening tool for AAT1 deficiency. For 6 months, all SPE carried out for any reasons were evaluated in our center. In those with less than 3% of alpha-1 globulins, AAT1 concentrations were studied. The SERPINA1 gene was subsequently sequenced in those patients displaying concentrations below 100 mg/dL. Out of the total, 14 patients (0.3%) were identified with low AAT1 concentrations, with 11 of them agreeing to enter the study. Of those, mutations in the SERPINA1 gene were discovered in 10 patients (91%). Heterozygous mutations were detected in seven patients; three had the c.1096G>A mutation (p.Glu366Lys; Pi*Z), two had the c.863A>T mutation (p.Glu288Val; Pi*S), one had the c.221_223delTCT mutation (p.Phe76del; Pi*Malton), and the last one had the c.1066G>A (p.Ala356Thr) mutation, which was not previously described. Finally, one patient had the c.863A>T mutation in homozygosis, whereas two double heterozygous patients c.863A>T/c.1096G>A were detected. An altered result in the concentration of AAT1 anticipates a mutation in the SERPINA1 gene in a manner close to 91%. The relationship between a decrease in the alpha-1 globulin band of the SPE and an alteration in the AAT1 concentration is direct in basal states of health. The SPE is presented as a highly sensitive test for opportunistic screening of AAT1 deficiency.

Diagnostic and Management Issues in Patients with Late-Onset Ornithine Transcarbamylase Deficiency.

Ornithine transcarbamylase deficiency (OTCD) is the most common inherited disorder of the urea cycle and, in general, is transmitted as an X-linked recessive trait. Defects in the OTC gene cause an impairment in ureagenesis, resulting in hyperammonemia, which is a direct cause of brain damage and death. Patients with late-onset OTCD can develop symptoms from infancy to later childhood, adolescence or adulthood. Clinical manifestations of adults with OTCD vary in acuity. Clinical symptoms can be aggravated by metabolic stressors or the presence of a catabolic state, or due to increased demands upon the urea. A prompt diagnosis and relevant biochemical and genetic investigations allow the rapid introduction of the right treatment and prevent long-term complications and mortality. This narrative review outlines challenges in diagnosing and managing patients with late-onset OTCD.

A Systematic Review: Do the Use of Machine Learning, Deep Learning, and Artificial Intelligence Improve Patient Outcomes in Acute Myocardial Ischemia Compared to Clinician-Only Approaches?

Cardiovascular diseases (CVDs) present a significant global health challenge and remain a primary cause of death. Early detection and intervention are crucial for improved outcomes in acute coronary syndrome (ACS), particularly acute myocardial infarction (AMI) cases. Artificial intelligence (AI) can detect heart disease early by analyzing patient information and electrocardiogram (ECG) data, providing invaluable insights into this critical health issue. However, the imbalanced nature of ECG and patient data presents challenges for traditional machine learning (ML) algorithms in performing unbiasedly. Investigators have proposed various data-level and algorithm-level solutions to overcome these challenges. In this study, we used a systematic literature review (SLR) approach to give an overview of the current literature and to highlight the difficulties of utilizing ML, deep learning (DL), and AI algorithms in predicting, diagnosing, and prognosis of heart diseases. We reviewed 181 articles from reputable journals published between 2013 and June 15, 2023, focusing on eight selected papers for in-depth analysis. The analysis considered factors such as heart disease type, algorithms used, applications, and proposed solutions and compared the benefits of algorithms combined with clinicians versus clinicians alone. This systematic review revealed that the current ML-based diagnostic approaches face several open problems and issues when implementing ML, DL, and AI in real-life settings. Although these algorithms show higher sensitivities, specificities, and accuracies in detecting heart disease, we must address the ethical concerns while implementing these models into clinical practice. The transparency of how these algorithms operate remains a challenge. Nevertheless, further exploration and research in ML, DL, and AI are necessary to overcome these challenges and fully harness their potential to improve health outcomes for patients with AMI.

Child Sexual Abuse (CSA) Using Hypnosis

Child sexual abuse (CSA) is a global problem and a serious public health issue. Perpetrators often resort to threats and force to incapacitate their victims, including using hypnosis. The use of hypnosis increases the level of difficulty of clinical forensic examination by presenting a diagnostic issue and complicating the formulation of forensic medical expert opinions. This evidence-based case report (EBCR) aims at assessing the available evidence concerning the forensic examination and diagnosis of hypnosis-facilitated CSA. A comprehensive computer-based literature search was performed using several keywords related to the clinical question. The search yielded seven relevant articles. The articles were appraised using general critical appraisal questions from the Centre for Evidence-Based Medicine, University of Oxford. All articles suggest that there might be a place for hypnosis in a criminal investigation (‘forensic hypnosis’). The evidence on the correct application of forensic hypnosis and its benefits are, however, still inconclusive and conflicting. In cases of suspected sexual assault using hypnosis, forensic hypnosis could potentially help memory recall of the victim and aid forward-thinking in drawing a clear and unambiguous conclusion for the forensic medical expert opinion.

Outlook for CRISPR-based tuberculosis assays now in their infancy.

Tuberculosis (TB) remains a major underdiagnosed public health threat worldwide, being responsible for more than 10 million cases and one million deaths annually. TB diagnosis has become more rapid with the development and adoption of molecular tests, but remains challenging with traditional TB diagnosis, but there has not been a critical review of this area. Here, we systematically review these approaches to assess their diagnostic potential and issues with the development and clinical evaluation of proposed CRISPR-based TB assays. Based on these observations, we propose constructive suggestions to improve sample pretreatment, method development, clinical validation, and accessibility of these assays to streamline future assay development and validation studies.

Rabies experts on demand: A cross-sectional study describing the use of a rabies telehealth service.

Rabies expert on demand (REOD) telehealth service is provided by the U.S. Centers for Disease Control and Prevention (CDC) to assist public health practitioners, health providers, and the public to interpret national and international rabies prevention guidelines. REOD is staffed by subject matter experts of the CDC Poxvirus and Rabies Branch to assess each unique situation and provide evidence-based guidance to stakeholders. This study aims to describe the utilization of a rabies telehealth system and provide insight into common consultations. A cross-sectional study of the nature of inquiries to REOD was done using the data collected from September 1, 2017 to September 30, 2021. An inquiry tracking form and Microsoft Access database were developed to document all inquiries received. Inquired ones were summarized to determine the frequency of inquiries by month, category, and location. Over a 49-month period, REOD received 5228 inquiries. Peak inquiries (n = 108) occurred during August 2019. The most frequent inquiries received pertained to risk assessment and management of rabies exposures (n = 1109), requests for testing assistance (n = 912), consultation for suspected human rabies (n = 746), rabies exposures and post-bite treatment occurring internationally (n = 310), and consultation for deviations in the recommended pre- and postexposure prophylaxis regimen (n = 300). REOD is a global resource for consultation related to managing rabies exposures, diagnostic issues, and rabies control strategies. REOD is a regularly utilized CDC service, as the demand for up-to-date rabies guidance remains high. REOD fulfills a critical role for the interpretation and consultation on rabies prevention guidelines to stakeholder.

A risk-scoring model for the differential diagnosis of lentigo maligna and other atypical pigmented facial lesions of the face: the facial iDScore.

Due to progressive ageing of the population, the incidence of facial lentigo maligna (LM) of the face is increasing. Many benign simulators of LM and LMM, known as atypical pigmented facial lesions (aPFLs - pigmented actinic keratosis, solar lentigo, seborrheic keratosis, seborrheic-lichenoid keratosis, atypical nevus) may be found on photodamaged skin. This generates many diagnostic issues and increases the number of biopsies, with a subsequent impact on aesthetic outcome and health insurance costs. Our aim was to develop a risk-scoring classifier-based algorithm to estimate the probability of an aPFL being malignant. A second aim was to compare its diagnostic accuracy with that of dermoscopists so as to define the advantages of using the model in patient management. A total of 154 dermatologists analysed 1111 aPFLs and their management in a tele-dermatology setting: they performed pattern analysis, gave an intuitive clinical diagnosis and proposed lesion management options (follow-up/reflectance confocal microscopy/biopsy). Each case was composed of a dermoscopic and/or clinical picture plus metadata (histology, age, sex, location, diameter). The risk-scoring classifier was developed and tested on this dataset and then validated on 86 additional aPFLs. The facial Integrated Dermoscopic Score (iDScore) model consisted of seven dermoscopic variables and three objective parameters (diameter ≥ 8 mm, age ≥ 70 years, male sex); the score ranged from 0 to 16. In the testing set, the facial iDScore-aided diagnosis was more accurate (AUC=0.79 [IC 95% 0.757-0.843]) than the intuitive diagnosis proposed by dermatologists (average of 43.5%). In the management study, the score model reduced the number of benign lesions sent for biopsies by 41.5% and increased the number of LM/LMM cases sent for reflectance confocal microscopy or biopsy instead of follow-up by 66%. The facial iDScore can be proposed as a feasible tool for managing patients with aPFLs.

In silico study on antidiabetic and antioxidant activity of bioactive compounds in Ficus carica L

Hyperglycemia is one of the diagnostic issues in diabetes mellitus and is considered as a complex metabolic condition. It has been one of the most prevalent illnesses of the twenty-first century and still rising at an alarming rate across the globe and expected to impact 693 million individuals by 2045. Therefore, it is mandatory to develop more effective and safer treatments to manage diabetes. One of the ways to manage hyperglycemia is through inhibiting carbohydrate digestion and thereby lowering the glucose formation in the human body. The enzyme salivary amylase and pancreatic amylase is responsible for cleaving α-1,4-glucoside bond. Amylase inhibitors can lower blood glucose in diabetics by slowing digestion. Ficus carica is commonly known for its medicinal properties due to its various phytochemicals. In the present study, 10 phytochemicals present in F. carica compounds named, β-carotene, lutein, cyanidin-3-glucoside, gallic acid, luteolin, catechin, kaempferol, vanillic acid, peonidin-3-glucoside, and quercetin hydrate were taken to study their inhibition potential against pancreatic amylase and salivary amylase through molecular docking and molecular dynamics simulations. Further, density functional theory calculations are used to investigate the delocalization of electron density on the molecule as well as study ADME properties of the molecules take. A QSAR model has been developed using the binding energy obtained using molecular docking and thermodynamic parameters from DFT calculations. Communicated by Ramaswamy H. Sarma

A Metabolomics Assay to Diagnose Citrus Huanglongbing Disease and to Aid in Assessment of Treatments to Prevent or Cure Infection.

Citrus greening disease, or Huanglongbing (HLB), has devastated citrus crops globally in recent years. The causal bacterium, 'Candidatus Liberibacter asiaticus', presents a sampling issue for qPCR diagnostics and results in a high false negative rate. In this work, we compared six metabolomics assays to identify HLB-infected citrus trees from leaf tissue extracted from 30 control and 30 HLB-infected trees. A liquid chromatography-mass spectrometry-based assay was most accurate. A final partial least squares-discriminant analysis (PLS-DA) model was trained and validated on 690 leaf samples with corresponding qPCR measures from three citrus varieties (Rio Red grapefruit, Hamlin sweet orange, and Valencia sweet orange) from orchards in Florida and Texas. Trees were naturally infected with HLB transmitted by the insect vector Diaphorina citri. In a randomized validation set, the assay was 99.9% accurate to classify diseased from nondiseased samples. This model was applied to samples from trees receiving plant defense-inducer compounds or biological treatments to prevent or cure HLB infection. From two trials, HLB-related metabolite abundances and PLS-DA scores were tracked longitudinally and compared with those of control trees. We demonstrate how our assay can assess tree health and the efficacy of HLB treatments and conclude that no trialed treatment was efficacious.

Prevalence and adverse consequences of delayed diagnosis and misdiagnosis in thrombotic antiphospholipid syndrome. An observational cohort study and a review of the literature

ObiectivesThis study aims to prospectively evaluate the frequency and adverse consequences of diagnostic delay and misdiagnosis in a cohort of patients with thrombotic antiphospholipid syndrome (TAPS). In addition, a systematic review of the literature concerning the diagnostic delay and misdiagnosis of TAPS was carried out.MethodsPatient enrollment occurred between 1999 and 2022. The study group was formed by TAPS patients whose diagnosis was delayed and those who were misdiagnosed. The control group was made up of patients who were timely and correctly diagnosed with TAPS.ResultsThe literature review showed 42 misdiagnosed patients, 27 of them were in one retrospective cohort study and 15 in 13 case reports. One hundred sixty-one out of 189 patients (85.2%) received a timely, correct diagnosis of TAPS; 28 (14.8%) did not. The number of patients with diagnostic issues was significantly higher for the first period (1999–2010), and the number of patients with a correct diagnosis was significantly higher for the second one (2011–2022). When the clinical and laboratory characteristics of the patients with delayed diagnosis were compared with those with misdiagnosis, there was a significantly higher number of severe adverse consequences characterized by permanent disability or death in the latter group. The two most common types of misdiagnoses were systemic lupus erythematosus (6 cases, 46.1%) and cardiovascular diseases (4 cases, 30.8%).ConclusionsThe study demonstrates that although knowledge about TAPS has improved over time, diagnostic delays and errors remains to be addressed as they are strongly associated to adverse consequences.Key Points•Although knowledge of thrombotic antiphospholipid syndrome has improved over time, it is still limited.•Diagnostic delay and misdiagnosis are still an important issue that remains to be addressed as they are strongly associated to adverse consequences.•The three more frequent misdiagnoses are multiple sclerosis, systemic lupus erythematosus and cardiovascular diseases.

Nanodrugs systems for therapy and diagnosis of esophageal cancer.

With the increasing incidence of esophageal cancer, its diagnosis and treatment have become one of the key issues in medical research today. However, the current diagnostic and treatment methods face many unresolved issues, such as low accuracy of early diagnosis, painful treatment process for patients, and high recurrence rate after recovery. Therefore, new methods for the diagnosis and treatment of esophageal cancer need to be further explored, and the rapid development of nanomaterials has brought new ideas for solving this problem. Nanomaterials used as drugs or drug delivery systems possess several advantages, such as high drug capacity, adjustably specific targeting capability, and stable structure, which endow nanomaterials great application potential in cancer therapy. However, even though the nanomaterials have been widely used in cancer therapy, there are still few reviews on their application in esophageal cancer, and systematical overview and analysis are deficient. Herein, we overviewed the application of nanodrug systems in therapy and diagnosis of esophageal cancer and summarized some representative case of their application in diagnosis, chemotherapy, targeted drug, radiotherapy, immunity, surgery and new therapeutic method of esophageal cancer. In addition, the nanomaterials used for therapy of esophageal cancer complications, esophageal stenosis or obstruction and oesophagitis, are also listed here. Finally, the challenge and the future of nanomaterials used in cancer therapy were discussed.

The development and design of the Musical Functional Assessment Profile (MFAP) in autism

The Musical Functional Assessment Profile (MFAP) in autism has been developed as a specific music therapy observational assessment tool to provide qualitative and descriptive information about the functionality of the child on the autism spectrum. It allows for assessing seven developmental functions: social interaction, communication and language, flexibility and anticipation, symbolisation, memory functions, motor functions and sensory functions. The MFAP tries to value the strengths, challenges, difficulties, and supports provided, considering current autism diagnostic criteria and treatment issues viewed from the perspective of neurodiversity. It may also allow the delineation of music therapy treatment goals and intervention planning related to a person-centred and a strength-based approach. The development and design of the tool is presented, and its practical advantages and disadvantages are discussed. Further research studies are required to determine the precise scope and accuracy of this tool; future directions are established for its validity and reliability process.

Paraphilias: an update on nosology and diagnostic challenges

ABSTRACT Ever since the inception of paraphilias in the psychiatric nosological system, it has been in several controversies ranging from determining normal sexual behaviour from abnormal, role of culture, diagnosing paraphilia as deviant sexual behaviour and various medico-legal issues related to sexual offenders and predators. Over the years, several landmark changes have been made in the subsection of paraphilias in both DSM and ICD nosological system. The evolutionary journey of paraphilias to paraphilic disorder is remarkable, yet there are various unresolved issues related to its nosological status and diagnosis. To review some fundamental concepts of paraphilias related to its evolution in nosological systems and discuss its various diagnostic and medico-legal/forensic issues. A comprehensive literature search was conducted on paraphilias in PubMed and Google Scholar and through the cross-references of relevant articles till June 2022. Keywords included ‘paraphilias,’ ‘nosology,’ ‘critique’ ‘issues’ and ‘diagnosis’ in various combinations. Only original articles (abstract and full text), review articles, viewpoint articles and recommendations published in English, till June 2022, were reviewed and checked thoroughly. Articles published in non-English languages were excluded. 34 articles related to the topic were found, including those relevant to paraphilias’ nosology and diagnostic issues. We discuss in detail the nosological journey of paraphilias and various controversies related to it. Additionally, we discuss the various diagnostic and forensic issues. From our review, we conclude that the most valid indicators of true paraphilic disorders i.e. exclusiveness, fixation and compulsiveness, which are the most complex entities to establish in a forensic context, are not adequately addressed even by the new criteria of DSM-5 and ICD-11 of paraphilic disorders. Hence, even after so many modifications, paraphilic disorders still present challenges to our conceptualization of mental disorders.

Cortical blindness: diagnostic issues in sudden bilateral visual loss

Cortical blindness is defined as bilateral visual loss due to disruption of the visual pathways beyond the lateral geniculate body. Visual disturbance as a result of cortical lesion can manifest in different ways. Anton's syndrome is one of the manifestations of cortical blindness, which presents as denial of loss of vision associated with confabulation in the setting of obvious visual loss. This case illustrates the challenges of diagnosing cortical blindness in the emergency setting.

SUPER-SENSITIVE REGISTRATION OF POLYFUNCTIONAL MAGNETIC NANOMATERIALS FOR THE RAPID DETERMINATION OF MOLECULAR MARKERS OF DISEASES

Magnetic particles (MPs) based on superparamagnetic iron oxide nanocrystals are increasingly used in modern research for the development of express technologies for high-precision determination of the concentration of biomolecules. In this work, we developed a universal method for using MPs as polyfunctional agents that perform several different functions in one analysis for topical issues of biochemical and medical diagnostics, based on the original technology of ultrasensitive detection of nonlinear magnetic nanomaterials. The method was tested for the rapid quantitative registration of cardiac markers and SARS-CoV-2-associated molecular markers in complex matrices. The proposed method is promising for creating test systems for prehospital monitoring, particularly for emergency molecular diagnostics in patients with suspected acute myocardial infarction, as well as for the rapid detection of coronavirus infection.

CSF3R-mutant chronic myelomonocytic leukemia is a distinct clinically subset with abysmal prognosis: a case report and systematic review of the literature

Chronic myelomonocytic leukemia (CMML) is a myelodysplastic syndrome/myeloproliferative neoplasm (MDS/MPN) chacaterized by persistent peripheral blood monocytosis, hypercellular bone marrow and dysplasia at least in one myeloid lineage. CMML shares much of its molecular landscape with other myeloid neoplasms, while differs from others such as chronic neutrophilic leukemia (CNL), given the high frequency of CSF3R mutations in the latter. In this article, we report a case of CSF3R-mutated CMML and dissect this rare entity by reviewing the medical literature, with the intent to understand how this rare mutation shapes CMML's clinical and morphological phenotype. CSF3R-mutated CMML emerges as a rare entity meeting the ICC/WHO diagnostic criteria for CMML and simultaneously showing clinical-pathological and molecular traits of CNL and atypical chronic myeloid leukemia, rising an important and difficult diagnostic and therapeutical issue.

Evaluation of the Patient With Paroxysmal Spells Mimicking Epileptic Seizures.

The diagnostic issue of paroxysmal spells, including epileptic seizure (ES) mimics, is one that neurologists frequently encounter. This review provides an up-to-date overview of the most common causes of ES mimics encountered in the outpatient setting. Paroxysmal spells are characterized by changes in awareness, attention, perception, or abnormal movements. These can be broadly classified as ES and nonepileptic spells (NES). NES mimics ES but are distinguished by their symptomatology and lack of epileptiform activity on electroencephalography. NES may have psychological or physiological underpinnings. Psychogenic non-ES are the most common mimics of ES. Physiological causes of NES include syncope, cerebrovascular, movement, and sleep-related disorders. Distinguishing NES from ES at times may be challenging even to the most experienced clinicians. However, detailed history with an emphasis on the clinical clues, including taking a moment-by-moment history of the event from the patient and observers and physical examination, helps create an appropriate differential diagnosis to guide further diagnostic testing. An accurate diagnosis of NES prevents iatrogenic harm, including unnecessary exposure to antiseizure medications and overuse of health care resources. It also allows for the correct specialist referral and appropriate treatment.

Локальная диагностика наличия полярных сияний на основе интеллектуального анализа геомагнитных данных

Despite the existing variety of approaches to monitoring space weather and geophysical parameters in the auroral oval region, the issue of effective prediction and diagnostics of auroras as a special state of the upper ionosphere at high latitudes remains virtually unresolved.
 In this paper, we explore the possibility of local diagnostics of auroras through mining of geomagnetic data from ground-based sources. We assess the significance of indicative variables and their statistical relationship.
 So, for example, the application of Bayesian inference to the data from the Lovozero geophysical station for 2012–2020 has shown that the dependence of a posteriori probability of observing auroras in the optical range on the state of geomagnetic parameters is logarithmic, and the degree of its significance is inversely proportional to the discrepancy between empirical data and approximating function.
 The accuracy of the approach to diagnostics of aurora presence based on the random forest method is at least 86 % when using several local predictors and ~80 % when using several global geomagnetic activity indices characterizing the geomagnetic field disturbance in the auroral zone.
 In conclusion, we discuss promising ways to improve the quality metrics of diagnostic models and their scope.

Local diagnostics of aurora presence based on intelligent analysis of geomagnetic data

Despite the existing variety of approaches to monitoring space weather and geophysical parameters in the auroral oval region, the issue of effective prediction and diagnostics of auroras as a special state of the upper ionosphere at high latitudes remains virtually unresolved.
 In this paper, we explore the possibility of local diagnostics of auroras through mining of geomagnetic data from ground-based sources. We assess the significance of indicative variables and their statistical relationship.
 So, for example, the application of Bayesian inference to the data from the Lovozero geophysical station for 2012–2020 has shown that the dependence of a posteriori probability of observing auroras in the optical range on the state of geomagnetic parameters is logarithmic, and the degree of its significance is inversely proportional to the discrepancy between empirical data and approximating function.
 The accuracy of the approach to diagnostics of aurora presence based on the random forest method is at least 86 % when using several local predictors and ~80 % when using several global geomagnetic activity indices characterizing the geomagnetic field disturbance in the auroral zone.
 In conclusion, we discuss promising ways to improve the quality metrics of diagnostic models and their scope.

D-dimer: issues of laboratory diagnostics

D-dimer is a protein fragment, resulting from the breakdown of fibrin during fibrinolysis. D-dimer is considered to be a fairly informative indicator of thrombus formation, since the mechanism of its production starts simultaneously with the process of thrombus formation. A D-dimer test allows evaluating the combination of 2 factors at once: coagulation and fibrinolysis. The marker makes it possible to timely detect their imbalance in case of diseases of the circulatory system (varicose veins, thrombophilia, pulmonary embolism).