Integrative Diagnostic Approach Research Articles

How to assess and treat right ventricular electromechanical dyssynchrony in post-repair tetralogy of Fallot: insights from imaging, invasive studies, and computational modelling.

Right bundle branch block (RBBB) and resulting right ventricular (RV) electromechanical discoordination are thought to play a role in the disease process of subpulmonary RV dysfunction that frequently occur post-repair tetralogy of Fallot (ToF). We sought to describe this disease entity, the role of pulmonary re-valvulation, and the potential added value of RV cardiac resynchronization therapy (RV-CRT). Two patients with repaired ToF, complete RBBB, pulmonary regurgitation, and significantly decreased RV function underwent echocardiography, cardiac magnetic resonance, and an invasive study to evaluate the potential for RV-CRT as part of the management strategy. The data were used to personalize the CircAdapt model of the human heart and circulation. Resulting Digital Twins were analysed to quantify the relative effects of RV pressure and volume overload and to predict the effect of RV-CRT. Echocardiography showed components of a classic RV dyssynchrony pattern which could be reversed by RV-CRT during invasive study and resulted in acute improvement in RV systolic function. The Digital Twins confirmed a contribution of electromechanical RV dyssynchrony to RV dysfunction and suggested improvement of RV contraction efficiency after RV-CRT. The one patient who underwent successful permanent RV-CRT as part of the pulmonary re-valvulation procedure carried improvements that were in line with the predictions based on his Digital Twin. An integrative diagnostic approach to RV dysfunction, including the construction of Digital Twins may help to identify candidates for RV-CRT as part of the lifetime management of ToF and similar congenital heart lesions.

Adult type diffuse gliomas in the new 2021 WHO Classification.

Adult-type diffuse gliomas represent a group of highly infiltrative central nervous system tumors with a prognosis that significantly varies depending on the specific subtype and histological grade. Traditionally, adult-type diffuse gliomas have been classified based on their morphological features with a great interobserver variability and discrepancy in patient survival even within the same histological grade. Over the last few decades, advances in molecular profiling have drastically changed the diagnostic approach and classification of brain tumors leading to the development of an integrated morphological and molecular classification endowed with a more clinically relevant value. These concepts were largely anticipated in the revised fourth-edition of WHO classification of central nervous system tumors published in 2016. The fifth-edition (WHO 2021) moved molecular diagnostics forward into a full integration of molecular parameters with the histological features into an integrative diagnostic approach. Diagnosis of adult type diffuse gliomas, IDH mutant and IDH-wildtype has been simplified by introducing revised diagnostic and grading criteria. In this review, we will discuss the most recent updates to the classification of adult-type diffuse gliomas and summarize the essential diagnostic keys providing a practical guidance to pathologists.

Gas path fault diagnosis of aircraft engine using HELM and transfer learning

Gas-path fault diagnosis of an aero-engine is a key challenge for flight safety. However, there are two problems: 1) Large collections of healthy condition samples and few fault samples; 2) The diagnosis accuracy cannot meet the practical demands. Therefore this paper proposes a new integrative diagnostic approach for gas-path fault of an aircraft engine to overcome the limitations. A novel model (HELM-TL) is presented to improve fault diagnosis performance, which ensembles the advantages of HELM and transfer learning by fusing target domain data and source domain data effectively. The attention mechanism is adopted to construct global dependency of gas-path monitoring data. Furthermore, this paper develops a novel algorithm for fault diagnosis which dynamically updates learning rate according to loss function. The proposed approach not only obtains more accurate fault distribution, but also avoids over-fitting problem, which greatly improves diagnosis performance and generalization. Finally, experimental data from China Eastern Airlines is adopted to validate. The experimental results show that proposed method has excellent robust according to sensitivity analysis. Moreover, it achieves a good tradeoff between diagnosis accuracy, transfer performance, and runtime cost. The proposed method also improves training accuracy by 5%–15%, reduces RMSE of fault diagnosis by 11%, and improves prediction accuracy by 12.1% compared with the average value of state-of-the-art methods.

Status of liquid profiling in precision oncology – the need for integrative diagnostics for successful implementation into standard care

Abstract The liquid profiling approach is currently at the threshold of translation from research application in various clinical trials to introduction into the management of cancer patients in the context of clinical care. Routine application has focused primarily on the analysis of single blood-based biomarkers for companion diagnostics. However, liquid profiling promises much broader diagnostic potential, which is discussed and illustrated in this manuscript through several case reports. These clinical cases range from identification of druggable targets to the detection of subclonal resistance mechanisms. In addition, liquid profiling can be used in clinical practice to identify complex molecular patterns or as a personalized tumor marker for patient-specific monitoring of response to treatment. These examples highlight both the value and limitations of liquid profiling in various clinical settings, which could be overcome by an integrative diagnostic approach with imaging techniques. The complementary advantages of both diagnostics approaches will allow combining high sensitivity with genetic tumor profiling and topologic assignment. Therefore, we advocate interdisciplinary integrated collaboration between laboratory and imaging experts to unravel the potentials of precision diagnostics in cancer care.

The value proposition of integrative diagnostics for (early) detection of cancer. On behalf of the EFLM interdisciplinary Task and Finish Group "CNAPS/CTC for early detection of cancer".

Disruptive imaging and laboratory technologies can improve clinical decision processes and outcomes in oncology. However, certain obstacles must be overcome before these technologies can be fully implemented as part of the standard for care. An integrative diagnostic approach represents a unique opportunity to unleash the full diagnostic potential and paves the way towards personalized cancer diagnostics. To meet this demand, an interdisciplinary Task Force of the EFLM was initiated as a consequence of an EFLM/ESR during the CELME 2019 meeting in order to evaluate the clinical value of CNAPS/CTC (circulating nucleic acids in plasma and serum/circulating tumor cells) in early detection of cancer. Here, an overview of current disruptive techniques, their clinical implications and potential value of an integrative diagnostic approach isprovided. Furthermore, requirements such as the establishment of diagnostic tumor boards, development of adequate software solutions and a change of mindset towards a new generation of diagnosticians providing actionable health information are presented. This development has the potential to elevate the position and clinical recognition of diagnosticians.

Zoonotic Dirofilaria immitis and Dirofilaria repens infection in humans and an integrative approach to the diagnosis

Dirofilariosis by Dirofilaria immitis and Dirofilaria repens is endemic in dogs from countries of the Mediterranean basin. Both species may infect humans, with most of the infected patients remaining asymptomatic. Based on the recent description of the southernmost hyperendemic European focus of heartworm disease in dogs from the Pelagie archipelagos, we performed a serological and molecular survey in human population of that area. Human blood samples were collected in the islands of Linosa (n=101) and Lampedusa (n=296) and tested by ELISA and molecular test for the detection of D. immitis and D. repens. Samples were also screened for filarioid-associated endosymbionts, Wolbachia sp. The seroprevalence of D. immitis and D. repens was, respectively, 7.9% and 3.96% in Linosa, and 7.77% and 19.93% in Lampedusa. Out of 397 human blood samples tested molecularly, 4 scored positive (1%) for Dirofilaria spp. by qPCR (i.e., three for D. immitis and one for D. repens) and 6 (1.5%) for Wolbachia. Of the qPCR positive for Dirofilaria spp., only D. repens was amplified by cPCR and was positive for Wolbachia. In the phylogenetic analysis, the sequence of Wolbachia detected in D. repens positive samples clustered along with other C supergroup filarioids. Our results overlap with the recent prevalence data collected on dogs from the same area, where D. immitis is prevalent in Linosa and D. repens prevails in Lampedusa. Molecular detection of D. immitis in human blood is quite unusual considering that humans are dead-end hosts for dirofilarial infection and most of the human cases described so far in Europe were ascribed to D. repens. An integrative diagnostic approach using serum analysis and Wolbachia detection is also presented. In endemic areas for canine dirofilarioses humans are exposed to the infection, suggesting the importance of One Health approach in diagnosing, treating and controlling this zoonotic parasitosis.

Cytopathology in the diagnostics of hematological diseases

Whereas in many fields of surgical pathology examination of cytological smears and analysis of histological tissue sections provide alternative methods which are chosen according to the clinical requirements, in hematopathology both types of morphological investigation are routinely applied in parallel and simultaneously. This procedure improves the diagnostic precision and safety. Unlike other European countries in Germany both procedures are performed by different specialties. Cytology is the responsibility of hematologists whereas histology is carried out by pathologists, which interferes with an integrative diagnostic approach unless intense communication takes place. Ideally, in the diagnosis of hematological disorders histology of bone marrow trephines should be studied in conjunction with smears of peripheral blood and bone marrow. In many instances, further complementary investigations, such as flow cytometry, cytogenetics and increasingly molecular pathological studies are necessary to guarantee an adequate modern state of diagnostics in hematopathology.

Bullous systemic lupus erythematosus – a case report

Bullous systemic lupus erythematosus (BSLE) is a rare but distinct disease, characterized by vesicobullous skin eruptions in systemic lupus erythematosus (SLE). It can arise either before or after a diagnosis of SLE has been established. BSLE is characterized by a dermatitis herpetiformis-like histology and an autoimmunity to type VII collagen. It must be differentiated from other autoimmune vesicobullous diseases such as epidermolysis bullosa acquisita, dermatitis herpetiformis, linear IgA disease, and bullous pemphigoid. A combination of clinical, histological, and immunofluorescence findings are necessary to establish a diagnosis of BSLE. We present a case of BSLE to illustrate and emphasize the need for an integrative diagnostic approach. DOI: http://dx.doi.org/10.3329/jdmc.v22i1.15691 J Dhaka Medical College, Vol. 22, No. 1, April, 2013, Page 90-92

Risk assessment, disease prevention and personalised treatments in breast cancer: is clinically qualified integrative approach in the horizon?

Breast cancer is a multifactorial disease. A spectrum of internal and external factors contributes to the disease promotion such as a genetic predisposition, chronic inflammatory processes, exposure to toxic compounds, abundant stress factors, a shift-worker job, etc. The cumulative effects lead to high incidence of breast cancer in populations worldwide. Breast cancer in the USA is currently registered with the highest incidence rates amongst all cancer related patient cohorts. Currently applied diagnostic approaches are frequently unable to recognise early stages in tumour development that impairs individual outcomes. Early diagnosis has been demonstrated to be highly beneficial for significantly enhanced therapy efficacy and possibly full recovery. Actual paper shows that the elaboration of an integrative diagnostic approach combining several levels of examinations creates a robust platform for the reliable risk assessment, targeted preventive measures and more effective treatments tailored to the person in the overall task of breast cancer management. The levels of examinations are proposed, and innovative technological approaches are described in the paper. The absolute necessity to create individual patient profiles and extended medical records is justified for the utilising by routine medical services. Expert recommendations are provided to promote further developments in the field.

Démarche sémiologique en TEMP/TDM osseuse. Une approche diagnostique intégrée de l’imagerie hybride

This article sketches out properties of the three modalities of bone scintigraphy: planar imaging, SPECT, SPECT/CT. Technical principles of SPECT/CT are developed. An integrative diagnostic approach of SPECT/CT patterns is then applied to malignant and benign skeletal conditions.

Diagnosis and Management of Cough Executive Summary: ACCP Evidence-Based Clinical Practice Guidelines

Recognition of the importance of cough in clinical medicine was the impetus for the original evidence-based consensus panel report on “Managing Cough as a Defense Mechanism and as a Symptom,” published in 1998,1 and this updated revision. Compared to the original cough consensus statement, this revision (1) more narrowly focuses the guidelines on the diagnosis and treatment of cough, the symptom, in adult and pediatric populations, and minimizes the discussion of cough as a defense mechanism; (2) improves on the rigor of the evidence-based review and describes the methodology in a separate section; (3) updates and expands, when appropriate, all previous sections; and (4) adds new sections with topics that were not previously covered. These new sections include nonasthmatic eosinophilic bronchitis (NAEB); acute bronchitis; nonbronchiectatic suppurative airway diseases; cough due to aspiration secondary to oral/pharyngeal dysphagia; environmental/occupational causes of cough; tuberculosis (TB) and other infections; cough in the dialysis patient; uncommon causes of cough; unexplained cough, previously referred to as idiopathic cough; an empiric integrative approach to the management of cough; assessing cough severity and efficacy of therapy in clinical research; potential future therapies; and future directions for research. To mitigate future diagnostic confusion, two new diagnostic terms have been introduced to replace two older terms that may represent misnomers. The committee unanimously recommends that the term upper airway cough syndrome (UACS) be used in preference to postnasal drip syndrome (PNDS) when discussing cough that is associated with upper airway conditions because it is unclear whether the mechanism of cough is postnasal drip, direct irritation, or inflammation of the cough receptors in the upper airway. The committee also recommends using the term unexplained cough rather than idiopathic cough because it is likely that more than one unknown cause of chronic cough will be discovered. The term idiopathic implies that one is dealing with only one disease. For managing adult patients with cough, the committee recommends an empiric, integrative diagnostic approach, which is presented in the section entitled “An Empiric Integrative Approach to the Management of Cough”.3 Guidelines for managing acute, subacute, and chronic cough are presented in algorithmic form (Fig 1–3). Guidelines with algorithms for evaluating chronic cough in pediatric patients < 15 years of age are presented in the section entitled “Guidelines for Evaluating Chronic Cough in Pediatrics”2,4 [Fig 4, ​,5].5]. For a full discussion on how to use the algorithms, please refer to these sections. Figure 1 Acute cough algorithm for the management of patients ≥ 15 years of age with cough lasting < 3 weeks. For diagnosis and treatment recommendations refer to the section indicated in the algorithm. PE = pulmonary embolism; Dx = diagnosis; ... Figure 3 Chronic cough algorithm for the management of patients ≥ 15 years of age with cough lasting > 8 weeks. ACE-I = ACE inhibitor; BD = bronchodilator; LTRA = leukotriene receptor antagonist; PPI = proton pump inhibitor. See the legend of ... Figure 4 Approach to a child 6 years of age and in some children ... Figure 5 Approach to a child ≤ 14 years of age with chronic specific cough (ie, cough associated with other features suggestive of an underlying pulmonary and/or systemic abnormality). Children > 14 years of age should be managed as outlined in ...

Novel integrative diagnostic approach for Crohn's disease

Novel integrative diagnostic approach for Crohn's disease

Diffuse Nonepidermolytic Palmoplantar Keratoderma Caused by a Recurrent Nonsense Mutation in DSG1

Mutations in genes coding for 2 desmosomal proteins, desmoglein 1 and desmoplakin, have been shown to cause autosomal dominant keratoderma palmoplantaris striata. We describe a family affected with a diffuse nonstriated form of palmoplantar keratoderma. Histopathologic examination of skin biopsy specimens disclosed cell-cell disadhesion in the suprabasal layers of the epidermis, as previously described in keratoderma palmoplantaris striata. We therefore genotyped all family members using microsatellite markers encompassing 3 keratoderma palmoplantaris striata-associated loci. Haplotype analysis suggested linkage of the disease to 18q12.1, which harbors the DSG1 gene, encoding desmoglein 1. Mutation analysis eventually led to the identification of a causative recurrent nonsense mutation in this gene. Mutations in DSG1 are not exclusively associated with striated palmoplantar keratoderma. The present study illustrates the efficacy of an integrative diagnostic approach to palmoplantar keratodermas involving clinical assessment, pathologic examination, microsatellite marker screening, and mutational analysis.

Dark Lumen Magnetic Resonance Enteroclysis in Combination With Mri Colonography for Whole Bowel Assessment in Patients With Crohnʼs Disease: First Clinical Experience

Magnetic resonance enteroclysis (MRE) is a recently introduced imaging technique that assesses the small bowel with similar sensitivity and specificity as the fluoroscopically performed conventional enteroclysis. Magnetic resonance imaging colonography (MRC) seems to be a promising technique for polyp assessment in the colon. In this feasibility study, we evaluated the combination of small bowel MRI with unprepared MRC as an integrative diagnostic approach of the whole bowel in patients with Crohn's disease. Thirty patients with known Crohn's disease were prospectively examined. No particular colonic preparation was applied. Applying the dark lumen technique in all patients, MRE and MRC were performed within 1 session using an integrative examination protocol. T2-weighted and contrast-enhanced T1-weighted sequences were acquired. Inflammation assessment (grades 0 to 2) of the colon was compared with conventional colonoscopy in 29 patient and with surgery in 1 patient. The entire colon was graded fair to good distended in all patients. In 11 of 210 evaluated colonic segments, feces hindered an adequate intraluminal bowel assessment. Twenty-three of 30 patients had complete colonoscopy as the gold standard. In 7 patients, complete colonoscopy could not be performed because of an inflamed stenosis. Correct grading of colonic inflammation was performed with 55.1% sensitivity and 98.2% specificity in all segments. Considering only more extensive inflammation (grade 2), the sensitivity of MRC increased to 70.2% with a specificity of 99.2%. The combination of MRE and MRC could improve the diagnostic value of abdominal MRI evaluation in patients with Crohn's disease. However, MRC can not replace conventional colonoscopy in subtle inflammation assessment.