Diagnostic Utility Research Articles

A growing number of AIs cleared for clinical use is finally available: The AI-assisted Pathologist

As more pathology laboratories are transitioning to a digital workflow, the availability of commercial Artificial Intelligence assistance systems is also increasing. Today nearly 40 such products approved for diagnostic use are available. This article provides an overview of the most widely addressed use cases, including Immunohistochemistry scoring for breast cancer and non-small-cell lung cancer, Gleason grading for prostate cancer, or metastasis detection in lymph nodes. While automation alone already promises an increase in efficiency that may help to bridge the growing gap between supply (pathology work force) and demand (histological testing), this article introduces another category of Artificial Intelligence products that go beyond just mimicking today’s established score. Various Artificial Intelligence are being introduced that detect genetic alterations or stratify risk, directly from the standard hematoxylin & eosin staining. Finally, a brief outlook explains how basic AI models are currently finding their way into computational pathology and promise to further accelerate product developments by decreasing the time-to-model.

Enhanced tuberculosis diagnosis with computer-aided chest X-ray and urine LAM in adults with HIV admitted to hospital (CASTLE study): A cluster randomised trial.

People with HIV (PHIV) admitted to hospital have high mortality, with tuberculosis (TB) being the major cause of death. Systematic use of new TB diagnostics could improve TB diagnosis and might improve outcomes. We conducted a cluster randomised trial among adult PHIV admitted to Zomba Central Hospital, Malawi. Admission-days were randomly assigned to: enhanced TB diagnostics using urine lipoarabinomannan (LAM) antigen tests (SILVAMP-LAM, Fujifilm, Japan and Determine-LAM, Alere/Abbot, USA), digital chest X-ray with computer aided diagnosis (dCXR-CAD, CAD4TBv6, Delft, Netherlands), plus usual care ("enhanced TB diagnostics"); or usual care alone ("usual care"). The primary outcome was TB treatment initiation during admission. Secondary outcomes were 56-day mortality, TB diagnosis within 24-hours, and undiagnosed TB at discharge, ascertained by culture of one admission sputum sample. Between 2 September 2020 and 15 February 2022, we recruited 419 people. Four people were excluded post-recruitment, leaving 415 adults recruited during 207 randomly assigned admission-days in modified intention-to-treat analysis. At admission, 90.8% (377/415) were taking antiretroviral therapy (ART) with median (IQR) CD4 cell count 240 cells/mm3. In the enhanced diagnostic arm, median CAD4TBv6 score was 60 (IQR: 51-71), 4.4% (9/207) had SILVAMP-LAM-positive and 14.4% (29/201) had Determine-LAM positive urine with three samples positive by both urine tests. TB treatment was initiated in 46/208 (22%) in enhanced TB diagnostics arm and 24/207 (12%) in usual care arm (risk ratio [RR] 1.92, 95% CI 1.20-3.08). There was no difference in mortality by 56 days (enhanced TB diagnosis: 54/208, 26%; usual care: 52/207, 25%; hazard ratio 1.05, 95% CI 0.72-1.53); TB treatment initiation within 24 hours (enhanced TB diagnosis: 8/207, 3.9%; usual care: 5/208, 2.4%; RR 1.61, 95% CI 0.53-4.71); or undiagnosed microbiological-confirmed TB at discharge (enhanced TB diagnosis, 0/207 (0.0%), usual care arm 2/208 (1.0%) (p = 0.50). Urine SILVAMP-LAM/Determine-LAM plus dCXR-CAD diagnostics identified more hospitalised PHIV with TB than usual care. The increase in TB treatment appeared mainly due to greater use of Determine-LAM, rather than SILVAMP-LAM or dCXR-CAD. Poor concordance between Determine-LAM and SILVAMP-LAM urine tests requires further investigation. Inpatient mortality for adults with HIV remains unacceptability high.

The diagnostic utility of cell block as an adjunct to routine cytology

Despite the diagnostic utility of cell block in FNAC and fluid cytology, known for better cellular yield and improved diagnostic accuracy, the technique remains to be underutilized for diagnosing neoplastic lesions.In this paper, a hospital based prospective study of 195 samples was conducted on cytological samples with the aim (a) to evaluate the diagnostic utility of cell block as an adjunct to routine cytological evaluation of aspiration and effusion fluid specimens, (b) To correlate the findings of routine cytology, cell block and routine histopathological examination wherever possible and (c) to explore the possibility of using ancillary techniques such as immunohistochemistry on cell blocks. The study revealed, most of the patients were between 51- 60 years with female preponderance. Among 195 samples, 79 (40.5%) were peritoneal fluids and 85 (43.5%) were lymph node. The diagnosis on conventional smear and cell block showed 71 (36.5%) cases and 68 (35%) cases were negative for malignancy respectively. 6 (3%) cases and 4 (2%) cases were suspicious for malignancy respectively. 118 (60.5%) cases and 123 (63%) cases were positive for malignancy respectively. Amongst the peritoneal effusion the most common primary site was ovary whereas majority of the primary site was unknown in lymph node FNAC. Peritoneal effusion showed 8 additional cases as positive for malignancy in CB preparation which were negative or suspicious for malignancy on CS. In FNAC, two additional positive case was found in CB preparation of lymph node. A Kappa value of 89.5 % for statistical correlation between Conventional smear and cell block preparation was calculated. The use of Cell block technique increases the detection of malignancy when used as an adjunct to conventional smears. Cell block technique is simple, inexpensive and reliable adjuvant to smears and it is recommended for routine cytological diagnosis and for application of immunomarkers and molecular studies.

Nerve conduction study on the split-hand plus index in Amyotrophic lateral sclerosis: correlations with lower motor neuron impairment.

In the arms of patients with Amyotrophic lateral sclerosis (ALS) two peculiar patterns of dissociated muscular atrophy have been described: the split-hand sign (with predominant atrophy of the lateral aspect of the hand, compared to hypothenar eminence) and the split-hand-plus sign (SHPS), a predominant abductor pollicis brevis (ABP) atrophy with sparing of flexor pollicis longus (FPL). In this case-control study, we evaluated the diagnostic utility of a neurophysiological indicator of SHPS and assessed its association with clinical features. We prospectively studied 59 incident ALS patients, 61 patients with ALS-mimic disorders (OND) and 61 non-neurological controls (NNCs). ABP and FPL compound muscle action potentials (CMAP) amplitudes were obtained by supramaximal stimulation of median nerve at elbow. Split-hand plus index (SHPI) was calculated according to the formula: APB-CMAP/FPL-CMAP. SHPI was significantly lower in ALS compared to OND patients and NNCs (p < 0.0001). SHPI value < 1 was observed in 2% of NNCs and 9% of OND patients and demonstrated an accuracy of 71% in differentiating ALS from OND and an accuracy of 74% in differentiating ALS from NNC. SHPI was associated with higher LMN score, and higher disease severity as quantified by the ALSFRS-r. Our results indicate that SHPI is a reliable indicator to distinguish ALS patients from ONDs and NNCs. SHPI was significantly associated to the degree of lower motor neuron impairment but showed no association with upper motoneuron impairment.

Sensitivity of miRNA-181a, miRNA-23b and miRNA-16 in the Late-Onset Neonatal Sepsis: A Diagnostic Study

Abstract Objective The study aimed to evaluate the expression and diagnostic value of levels of the microRNAs (miRNAs), miRNA-181a, miRNA-23b, and miRNA-16, in late-onset neonatal sepsis (LOS) and compare them with the diagnostic utility of C-reactive protein (CRP) levels. Methods This was a prospective diagnostic study conducted between January 2021 and March 2023 at a tertiary care center (Sri Ramachandra Hospital) in India. Quantitative real-time polymerase chain reaction was performed to determine miRNA-181a, miRNA-23b, and miRNA-16 expression levels, and CRP was measured by nephelometry. The diagnostic value of miRNA and CRP levels were analyzed using receiver operating characteristic (ROC) curves. ROC curves were utilized to determine optimal cutoff points, and Mann–Whitney tests were performed using SPSS to ascertain P values, with statistical significance defined as &lt;0.05. Results This study included 100 samples, with 50 cases of culture-proven LOS (27 female, 23 male) and 50 healthy controls (31 female, 19 male). In LOS, miRNA-181a and miRNA-23b expression levels were significantly downregulated (P &lt; 0.001), with area under the curve (AUC) values of 0.83 and 0.92, respectively, whereas those of miRNA-16 were significantly upregulated (P &lt; 0.001; AUC = 0.97). In comparison, CRP levels had an AUC value of 0.831 (P &lt; 0.001). Further, miRNA-23b showed the highest sensitivity (98%) of markers tested, whereas miRNA-16 exhibited the highest specificity (96%). Conclusion MiRNA, especially miRNA-16, shows diagnostic potential for neonatal sepsis compared with traditional biomarkers like CRP and procalcitonin, suggesting its use as an early marker for LOS. However, further cohort studies are needed before practical application.

Diagnostic accuracy and clinical utility of the PHQ-2 and GAD-2: a comparison with long-format measures for depression and anxiety

BackgroundAnxiety and depression are highly prevalent and often comorbid mental disorders that are encompassed within the broad category of emotional disorders. The frequent comorbidity of anxiety and depression can pose challenges for accurate diagnosis and treatment which, in turn, highlights the need for reliable measurements that are simultaneously responsive to change and prevent non-response bias. Brief measures of anxiety and depression can potentially increase response rates due to their brevity and ease of administration. This study evaluates the psychometric characteristics, discriminative accuracy, and sensitivity to change of the Generalized Anxiety Disorder 2-item scale (GAD-2) and the Patient Health Questionnaire 2-item scale (PHQ-2) within a clinical population.MethodThe sample comprised treatment-seeking participants (n = 3,411), screened (n = 2,477) to receive an internet-based psychotherapeutic intervention (cognitive-behavioral, psychodynamic, or waitlist).ResultsBrief measures can effectively detect individuals who may be eligible for a diagnosis of depression and anxiety, not only prior to but also during and following the completion of psychological treatment. The discriminative ability of the GAD-2 was significantly greater during active treatment and at post-assessment compared with pre-treatment screening, although no such differences were found for the PHQ-2. Finally, endorsing the most severe response option on the GAD-2 and PHQ-2 was associated with a high probability of presenting with clinically relevant anxiety and depressive symptoms.ConclusionBrief measures of anxiety and depression are viable instruments to screen for and monitor anxiety and depressive symptoms.Clinical trial registrationClinicalTrials.gov, identifier NCT05016843.

The association between the neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and monocyte-to-lymphocyte ratio and systemic sclerosis and its complications: a systematic review and meta-analysis

IntroductionThe identification of new, easily measurable biomarkers might assist clinicians in diagnosing and managing systemic sclerosis (SSc). Although the full blood count is routinely assessed in the evaluation of SSc, the diagnostic utility of specific cell-derived inflammatory indices, i.e., neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and monocyte-to-lymphocyte ratio (MLR), has not been critically appraised in this patient group.MethodsWe conducted a systematic review and meta-analysis of studies investigating the NLR, PLR, and MLR, in SSc patients and healthy controls and in SSc patients with and without relevant complications. PubMed, Scopus, and Web of Science were searched from inception to 23 February 2024. Risk of bias and certainty of evidence were assessed using validated tools.ResultsIn 10 eligible studies, compared to controls, patients with SSc had significantly higher NLR (standard mean difference, SMD=0.68, 95% CI 0.46 to 0.91, p&amp;lt;0.001; I2 = 74.5%, p&amp;lt;0.001), and PLR values (SMD=0.52, 95% CI 0.21 to 0.83, p=0.001; I2 = 77.0%, p=0.005), and a trend towards higher MLR values (SMD=0.60, 95% CI -0.04 to 1.23, p=0.066; I2 = 94.1%, p&amp;lt;0.001). When compared to SSc patients without complications, the NLR was significantly higher in SSc with interstitial lung disease (ILD, SMD=0.31, 95% CI 0.15 to 0.46, p&amp;lt;0.001; I2 = 43.9%, p=0.11), pulmonary arterial hypertension (PAH, SMD=1.59, 95% CI 0.04 to 3.1, p=0.045; I2 = 87.6%, p&amp;lt;0.001), and digital ulcers (DU, SMD=0.43, 95% CI 0.13 to 0.74, p=0.006; I2 = 0.0%, p=0.49). The PLR was significantly higher in SSc patients with ILD (SMD=0.42, 95% CI 0.25 to 0.59, p&amp;lt;0.001; I2 = 24.8%, p=0.26). The MLR was significantly higher in SSc patients with PAH (SMD=0.63, 95% CI 0.17 to 1.08, p=0.007; I2 = 66.0%, p=0.086), and there was a trend towards a higher MLR in SSc patients with ILD (SMD=0.60, 95% CI -0.04 to 1.23, p=0.066; I2 = 94.1%, p&amp;lt;0.001).DiscussionPending the results of appropriately designed prospective studies, the results of this systematic review and meta-analysis suggest that blood cell-derived indices of inflammation, particularly the NLR and PLR, may be useful in the diagnosis of SSc and specific complications.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/, identifier CRD42024520040.

Angiographic tool to detect pulmonary arteriovenous malformations in single ventricle physiology.

Individuals with single ventricle physiology who are palliated with superior cavopulmonary anastomosis (Glenn surgery) may develop pulmonary arteriovenous malformations. The traditional tools for pulmonary arteriovenous malformation diagnosis are often of limited diagnostic utility in this patient population. We sought to measure the pulmonary capillary transit time to determine its value as a tool to identify pulmonary arteriovenous malformations in patients with single ventricle physiology. We defined the angiographic pulmonary capillary transit time as the number of cardiac cycles required for transit of contrast from the distal pulmonary arteries to the pulmonary veins. Patients were retrospectively recruited from a single quaternary North American paediatric centre, and angiographic and clinical data were reviewed. Pulmonary capillary transit time was calculated in 20 control patients and compared to 20 single ventricle patients at the pre-Glenn, Glenn, and Fontan surgical stages (which were compared with a linear-mixed model). Correlation (Pearson) between pulmonary capillary transit time and haemodynamic and injection parameters was assessed using angiograms from 84 Glenn patients. Five independent observers calculated pulmonary capillary transit time to measure reproducibility (intraclass correlation coefficient). Mean pulmonary capillary transit time was 3.3 cardiac cycles in the control population, and 3.5, 2.4, and 3.5 in the pre-Glenn, Glenn, and Fontan stages, respectively. Pulmonary capillary transit time in the Glenn population did not correlate with injection conditions. Intraclass correlation coefficient was 0.87. Pulmonary angiography can be used to calculate the pulmonary capillary transit time, which is reproducible between observers. Pulmonary capillary transit time accelerates in the Glenn stage, correlating with absence of direct hepatopulmonary venous flow.

Clinicopathological and Molecular Analysis of Aqueous Humor for the Diagnosis of Feline Infectious Peritonitis

Background: This study was designed to assess the diagnostic utility for FIP of cytology, protein measurement and RT-PCR for feline coronaviruses (FCoV) on aqueous humor (AH), since little information is currently available. Methods: AH samples (n = 85) were collected post-mortem from 13 cats with effusive FIP (E-FIP), 15 with non-effusive FIP (NE-FIP) and 16 without FIP, to perform cytology (n = 83) and RT-PCR (n = 66) and to calculate their sensitivity, specificity and positive and negative likelihood ratios (LR+ and LR−). The protein concentration was measured on 80 fluids. Results: The proportion of RT-PCR positive samples did not differ among groups, while positive cytology was more frequent in samples with FIP (p = 0.042) or positive RT-PCR (p = 0.007). Compared with other groups, the protein concentration was higher in samples with NE-FIP (p = 0.017), positive RT-PCR (p = 0.005) or positive cytology (p &lt; 0.001). The specificity of cytology together with RT-PCR, cytology alone, RT-PCR alone and cytological proteinaceous background were 90.0%, 84.6%, 70.0%, 61.5%, and the LRs 3.48, 2.65, 1.83, 1.64, respectively. However, their sensitivities were low (34.8–63.0%) and their LR− high (0.60–0.72). Conclusions: Based on the LR+, cytology and/or RT-PCR may support the diagnosis when the pre-test probability of FIP is high. The concentration of intraocular protein is a promising marker, especially in NE-FIP.

Identification of CFH and FHL2 as biomarkers for idiopathic pulmonary fibrosis

BackgroundIdiopathic pulmonary fibrosis (IPF) is a fatal disease of unknown etiology with a poor prognosis, characterized by a lack of effective diagnostic and therapeutic interventions. The role of immunity in the pathogenesis of IPF is significant, yet remains inadequately understood. This study aimed to identify potential key genes in IPF and their relationship with immune cells by integrated bioinformatics analysis and verify by in vivo and in vitro experiments.MethodsGene microarray data were obtained from the Gene Expression Omnibus (GEO) for differential expression analysis. The differentially expressed genes (DEGs) were identified and subjected to functional enrichment analysis. By utilizing a combination of three machine learning algorithms, specific genes associated with idiopathic pulmonary fibrosis (IPF) were pinpointed. Then their diagnostic significance and potential co-regulators were elucidated. We further analyzed the correlation between key genes and immune infiltrating cells via single-sample gene set enrichment analysis (ssGSEA). Subsequently, a single-cell RNA sequencing data (scRNA-seq) was used to explore which cell types expressed key genes in IPF samples. Finally, a series of in vivo and in vitro experiments were conducted to validate the expression of candidate genes by western blot (WB), quantitative real-time PCR (qRT-PCR), and immunohistochemistry (IHC) analysis.ResultsA total of 647 DEGs of IPF were identified based on two datasets, including 225 downregulated genes and 422 upregulated genes. They are closely related to biological functions such as cell migration, structural organization, immune cell chemotaxis, and extracellular matrix. CFH and FHL2 were identified as key genes with diagnostic accuracy for IPF by three machine learning algorithms. Analysis using ssGSEA revealed a significant association of both CFH and FHL2 with diverse immune cells, such as B cells and NK cells. Further scRNA-seq analysis indicated CFH and FHL2 were specifically upregulated in human IPF tissues, which was confirmed by in vitro and in vivo experiments.ConclusionIn this study, CFH and FHL2 have been identified as novel potential biomarkers for IPF, with potential diagnostic utility in future clinical applications. Subsequent investigations into the functions of these genes in IPF and their interactions with immune cells may enhance comprehension of the disease’s pathogenesis and facilitate the identification of therapeutic targets.

Diagnostic utility of contrast-enhanced computed tomography for ectopic pregnancy.

Contrast-enhanced computed tomography (CECT) is an emergent diagnostic imaging modality to identify the bleeding site and survey the abdominal cavity. The diagnostic utility of CECT for ectopic pregnancy (EP) has not been well-investigated. The objective of this study was to evaluate the characteristics of CECT findings in patients with EP and extract specific findings that could contribute to the identification of implantation sites. We conducted a retrospective study, reviewing suspected EP cases between April 2015 and March 2018 in our hospital. Clinical symptoms, blood test results, transvaginal sonography findings, and surgical and pathologic findings from the medical records were assessed. CECT images were evaluated by a certified radiologist and gynecologist retrospectively in consensus. The following were selected as positive findings for specific determination of the ectopic implantation site: the ectopic gestational sac, lateralization of the hemoperitoneum around the adnexa on either side, and extravascular leakage of the contrast agent outside the uterine cavity. CECT was performed in 41 women with an EP. The ectopic implantation site was detectable on CECT in 90.2% (37/41), whereas it was noted in 70.0% (32/41) on transvaginal ultrasonography (TVS). Of nine patients with an EP with an undetectable implantation site on TVS, six were positive for the specific determination of the ectopic implantation site on CECT. CECT has the potential to predict ectopic implantation sites with high-level sensitivity. As CECT is an urgent diagnostic imaging tool to be used in an emergent setting, it may be a good option for EP diagnosis when the availability of magnetic resonance imaging is limited.

Neutrophil gelatinase-associated lipocalin (NGAL) levels for early prediction and ruling out future contrast nephropathy in patients undergoing primary coronary intervention

Abstract Funding Acknowledgements None. Background Neutrophil gelatinase-associated lipocalin (NGAL), is an early marker of acute kidney injury(AKI) . We aimed to investigate the diagnostic utility of sequential NGAL measurements for both prediction and ruling out of contrast induced AKI (CI-AKI) among patients with ST segment elevation (STEMI) undergoing primary coronary intervention (PCI). Methods We included 133 patients with STEMI treated with PCI. Blood samples for plasma NGAL were drawn immediately before PCI (NGAL 0) and 24 hours after PCI (NGAL 24). Optimal threshold for the development of CI-AKI were determined using receiver operating characteristic curves (ROC). Patients were also assessed for the dynamics between NGAL 0 and NGAL 24 levels. Results Mean age was 62 ±13 years and 78% were men, and a total of 20 (15%) developed CI-AKI . Patients with CI-AKI demonstrated higher plasma NGAL 0 levels (164 ± 42 vs. 95 ± 30 ng/mL; p &amp;lt; 0.001) as well as NGAL 24 levels (142 ± 41 vs. 93 ± 36 ng/mL; p &amp;lt; 0.001). There were no significant changes between NGAL 0 &amp; 24 hours within the 2 groups( figure 1). According to the ROC curve analysis (figure 2), the optimal NGAL 0 level for CI-AKI prediction was &amp;gt;125 ng/mL (AUC 0.841, 95% CI 0.801–0.961, p &amp;lt; 0.001), with a sensitivity of and specificity of 70% and 84% respectively, while the negative predictive value of NGAL 0&amp;lt;125 ng/mL was 94%. Conclusions Among STEMI patients, NGAL levels before primary PCI may be utilized both for ruling out and for the prediction of CI-AKI.NGAL 0 vs 24 according to CI-AKINGAL AUC

Flow cytometry-based method using diversity of cytokine production differentiates between Mycobacterium tuberculosis infection and disease

Authors present a pilot study of the development of innovative flow cytometry-based assay with a potential for use in tuberculosis diagnostics. Currently available tests do not provide robust discrimination between latent tuberculosis infection (TBI) and tuberculosis disease (TB). The desired application is to distinguish between the two conditions by evaluating the production of a combination of three cytokines: IL-2 (interleukin-2), IFNɣ (interferon gamma) and TNFɑ (tumor necrosis factor alpha) in CD4+ and CD8+ T cells.The study was conducted on 68 participants, divided into two arms according to age (paediatric and adults). Each arm was further split into three categories (non-infection (NI), TBI, TB) based on the immune reaction to Mycobacterium tuberculosis (M.tb) after a close contact with pulmonary TB. Each blood sample was stimulated with specific M.tb antigens present in QuantiFERON tubes (TB1 and TB2). We inferred TBI or TB based on the predominant cytokine response of the CD4+ and/or CD8+ T cells.Significant differences were detected between the NI, TBI and the TB groups in TB1 in the CD4+TNFɑ+parameter in children. Along with IL-2, TNFɑ seems to be the most promising diagnostic marker in both CD4+and CD8+ T cells. However, more detailed analyses on larger cohorts are needed to confirm the observed tendencies.

Re-assessing the diagnostic value of the enhancing "capsule" in hepatocellular carcinoma imaging.

The enhancing "capsule" (EC) in hepatocellular carcinoma (HCC) diagnosis has received varying degrees of recognition across major guidelines. This study aimed to assess the diagnostic utility of EC in HCC detection. We retrospectively analyzed patients who underwent pre-surgical computed tomography (CT) and hepatobiliary agent-enhanced magnetic resonance imaging (HBA-MRI) between January 2016 and December 2019. A single hepatic tumor was confirmed based on the pathology of each patient. Three radiologists independently reviewed the images according to the Liver Imaging Reporting and Data System (LIRADS) v2018 criteria and reached a consensus. Interobserver agreement for EC before reaching a consensus was quantified using Fleiss κ statistics. The impact of EC on the LI-RADS classification was assessed by comparing the positive predictive values for HCC detection in the presence and absence of EC. In total, 237 patients (median age, 60 years; 184 men) with 237 observations were included. The interobserver agreement for EC detection was notably low for CT (κ=0.169) and HBA-MRI (κ=0.138). The presence of EC did not significantly alter the positive predictive value for HCC detection in LI-RADS category 5 observations on CT (94.1% [80/85] vs. 94.6% [88/93], P=0.886) or HBA-MRI (95.7% [88/92] vs. 90.6% [77/85], P=0.178). The diagnostic value of EC in HCC diagnosis remains questionable, given its poor interobserver agreement and negligible impact on positive predictive values for HCC detection. This study challenges the emphasis on EC in certain diagnostic guidelines and suggests the need to re-evaluate its role in HCC imaging.

The Pathologically Evolving Aggregation-State of Cells in Cancerous Tissues as Interpreted by Fractal and Multi-Fractal Dispersion Theory in Saturated Porous Formations

A recent author’s fractal fluid-dynamic dispersion theory in porous media has focused on the derivation of the associated nonergodic (or effective) macrodispersion coefficients by a 3-D stochastic Lagrangian approach. As shown by the present study, the Fickian (i.e., the asymptotic constant) component of a properly normalized version of these coefficients exhibits a clearly detectable minimum in correspondence with the same fractal dimension (d ≅ 1.7) that seems to characterize the diffusion-limited aggregation state of cells in advanced stages of cancerous lesion progression. That circumstance suggests that such a critical fractal dimension, which is also reminiscent of the colloidal state of solutions (and may therefore identify the microscale architecture of both living and non-living two-phase systems in state transition conditions) may actually represent a sort of universal nature imprint. Additionally, it suggests that the closed-form analytical solution that was provided for the effective macrodispersion coefficients in fractal porous media may be a reliable candidate as a physically-based descriptor of blood perfusion dynamics in healthy as well as cancerous tissues. In order to evaluate the biological meaningfulness of this specific fluid-dynamic parameter, a preliminary validation is performed by comparison with the results of imaging-based clinical surveys. Moreover, a multifractal extension of the theory is proposed and discussed in view of a perspective interpretative diagnostic utilization.

Diagnostic utility of contrast-enhanced ultrasound endoscopy in a case of hemosuccus pancreaticus .

Diagnostic utility of contrast-enhanced ultrasound endoscopy in a case of hemosuccus pancreaticus .

Diagnostic yields and safety of thoracoscopic cryobiopsies in Japan: A single-center retrospective observational study

BackgroundThoracoscopy is useful for diagnosing unexplained pleural effusions. A sufficient specimen volume is often difficult to obtain using forceps biopsies (FBs) but can be obtained with pleural cryobiopsies (CBs). This study aimed to assess the utility and safety of CB during thoracoscopy in the Japanese population. MethodsPatients who underwent thoracoscopic CBs at the Japanese Red Cross Medical Center between January 2017 and August 2023 were included in the study. Data were retrospectively analyzed, including clinical data, thoracoscopic findings, specimen size, diagnostic yield, and complications. The number of collected specimens and the freezing time were left to the discretion of the attending physician. ResultsTwenty-six patients underwent thoracoscopic CB. Specimens obtained by CB were larger than those obtained by FB. Primary lung cancer was the most common cause of pleural effusion, followed by malignant pleural mesothelioma. CB contributed to the diagnosis in 24 of 26 cases (92.3%) and FB contributed to the diagnosis in 11 of 18 cases (61.1%). Severe fibrosis could be diagnosed in all 3 cases by CB, but not by FB. The common complications of CB included bleeding at the biopsy site and atelectasis, but no severe complications occurred. ConclusionsThe utility and safety of thoracoscopic CB for diagnosing pleural effusions in Japan were verified. The diagnostic yield, specimen size, and safety profile of CB support the diagnostic utility of this method.

Pseudo-NRBC in the Mindray BC-6800Plus analyzer: A clue for diagnostic anticipation of fungemia. Experimental and preliminary clinical reports.

Candidemia can be a significant cause of death in immunosuppressed or debilitated patients particularly. Abnormalities of the instrumental cytograms of some hematological analyzers, such as Mindray BC-6800Plus, can be related to circulating Candida. We studied the possible diagnostic usefulness of this information. A fungal bloodstream infection has been simulated by adding aliquots of Candida albicans, Candida parapsilosis, and Candida glabrata to 75 leftovers and anonymized peripheral blood samples. Cytographic abnormalities like those of experimental samples were used to select patients with possible fungemia. The microscopic review of peripheral blood smears constituted the confirmatory method. In all experimental samples, the various Candida types caused pseudo-NRBC and morphological abnormalities of WNB and DIFF cytograms. Circulating blastospores, free or engulfed by neutrophils, were the microscopic findings in the peripheral blood smears. In the clinical verification, 72 patients were recruited based on the presence of an evocative cluster in the WNB and DIFF cytograms. The microscopic review of 39 out of 72 samples was positive for NRBC. According to blood cultures, light microscopy revealed fungal forms of several Candida or non-Candida types in the remaining 33 samples. Nine of these cases were not yet known to suffer from bloodstream infection. Although further confirmatory clinical studies are required for these diagnostic abilities, the BC 6800Plus cytographic abnormalities related to fungemia have proven helpful in rapidly monitoring persistent fungemia in already diagnosed patients. In unknown or undiagnosed cases, they could be the trigger point for the subsequent diagnostic-therapeutic pathway.

Clinical validation of C12FDG as a marker associated with senescence and osteoarthritic phenotypes.

Chronic conditions associated with aging have proven difficult to prevent or treat. Senescence is a cell fate defined by loss of proliferative capacity and the development of a pro-inflammatory senescence-associated secretory phenotype comprised of cytokines/chemokines, proteases, and other factors that promotes age-related diseases. Specifically, an increase in senescent peripheral blood mononuclear cells (PBMCs), including T cells, is associated with conditions like frailty, rheumatoid arthritis, and bone loss. However, it is unknown if the percentage of senescent PBMCs associated with age-associated orthopedic decline could be used for potential diagnostic or prognostic use in orthopedics. Here, we report senescent cell detection using the fluorescent compound C12FDG to quantify PBMCs senescence across a large cohort of healthy and osteoarthritic patients. There is an increase in the percent of circulating C12FDG+ PBMCs that is commensurate with increases in age and senescence-related serum biomarkers. Interestingly, C12FDG+ PBMCs and T cells also were found to be elevated in patients with mild to moderate osteoarthritis, a progressive joint disease that is strongly associated with inflammation. The percent of C12FDG+ PBMCs and age-related serum biomarkers were decreased in a small subgroup of study participants taking the senolytic drug fisetin. These results demonstrate quantifiable measurements in a large group of participants that could create a composite score of healthy aging sensitive enough to detect changes following senolytic therapy and may predict age-related orthopedic decline. Detection of peripheral senescence in PBMCs and subsets using C12FDG may be clinically useful for quantifying cellular senescence and determining how and if it plays a pathological role in osteoarthritic progression.

Evaluation of serum cystatin C levels in multiple myeloma: diagnostic significance and clinical implications

Evaluation of serum cystatin C levels in multiple myeloma: diagnostic significance and clinical implications