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Diagnostics (Basel, Switzerland) Jun 2022CNN-based image processing has been actively applied to histopathological analysis to detect and classify cancerous tumors automatically. However, CNN-based classifiers...
CNN-based image processing has been actively applied to histopathological analysis to detect and classify cancerous tumors automatically. However, CNN-based classifiers generally predict a label with overconfidence, which becomes a serious problem in the medical domain. The objective of this study is to propose a new training method, called MixPatch, designed to improve a CNN-based classifier by specifically addressing the prediction uncertainty problem and examine its effectiveness in improving diagnosis performance in the context of histopathological image analysis. MixPatch generates and uses a new sub-training dataset, which consists of mixed-patches and their predefined ground-truth labels, for every single mini-batch. Mixed-patches are generated using a small size of clean patches confirmed by pathologists while their ground-truth labels are defined using a proportion-based soft labeling method. Our results obtained using a large histopathological image dataset shows that the proposed method performs better and alleviates overconfidence more effectively than any other method examined in the study. More specifically, our model showed 97.06% accuracy, an increase of 1.6% to 12.18%, while achieving 0.76% of expected calibration error, a decrease of 0.6% to 6.3%, over the other models. By specifically considering the mixed-region variation characteristics of histopathology images, MixPatch augments the extant mixed image methods for medical image analysis in which prediction uncertainty is a crucial issue. The proposed method provides a new way to systematically alleviate the overconfidence problem of CNN-based classifiers and improve their prediction accuracy, contributing toward more calibrated and reliable histopathology image analysis.
PubMed: 35741303
DOI: 10.3390/diagnostics12061493 -
Forensic Science, Medicine, and... Sep 2023The autopsy is considered the gold standard in death investigation. Performing an autopsy requires human and material resources that must be programmed in order to meet...
INTRODUCTION AND OBJECTIVES
The autopsy is considered the gold standard in death investigation. Performing an autopsy requires human and material resources that must be programmed in order to meet the demands of the judicial system. However, as far as we know, the cost of forensic autopsy in Spain has not been determined. Thus, the aim of this study was to estimate the cost of a standard autopsy in order to organise Forensic Pathology Services more efficiently.
MATERIAL AND METHODS
A micro-cost analysis was carried out. The nominal group technique was applied using a panel of 10 forensic experts in order to identify and quantify the resources associated with a forensic autopsy.
RESULTS
The results showed that analysis and studies are the most important item in the total cost (54.7%), followed by staff (20.5%), preservation of body (14%), single-use products (7%), equipment and stock (1.6%), cleaning and disinfection (1.5%), facilities maintenance (0.5%) and IT (0.2%).
CONCLUSIONS
The total cost of a standard autopsy was €1501.45, which is lower than the European average. This study is the first in Spain to calculate the unit price of a forensic autopsy by means of micro-cost analysis. This may help to address the way forensic pathology centres are organised at different levels of complexity.
Topics: Humans; Autopsy; Spain; Cause of Death; Forensic Medicine; Forensic Pathology
PubMed: 36342626
DOI: 10.1007/s12024-022-00534-w -
Technology in Cancer Research &... 2023Pap smear is considered to be the primary examination for the diagnosis of cervical cancer. But the analysis of pap smear slides is a time-consuming task and tedious as...
Pap smear is considered to be the primary examination for the diagnosis of cervical cancer. But the analysis of pap smear slides is a time-consuming task and tedious as it requires manual intervention. The diagnostic efficiency depends on the medical expertise of the pathologist, and human error often hinders the diagnosis. Automated segmentation and classification of cervical nuclei will help diagnose cervical cancer in earlier stages. The proposed methodology includes three models: a Residual-Squeeze-and-Excitation-module based segmentation model, a fusion-based feature extraction model, and a Multi-layer Perceptron classification model. In the fusion-based feature extraction model, three sets of deep features are extracted from these segmented nuclei using the pre-trained and fine-tuned VGG19, VGG-F, and CaffeNet models, and two hand-crafted descriptors, Bag-of-Features and Linear-Binary-Patterns, are extracted for each image. For this work, Herlev, SIPaKMeD, and ISBI2014 datasets are used for evaluation. The Herlev datasetis used for evaluating both segmentation and classification models. Whereas the SIPaKMeD and ISBI2014 are used for evaluating the classification model, and the segmentation model respectively. The segmentation network enhanced the precision and ZSI by 2.04%, and 2.00% on the Herlev dataset, and the precision and recall by 0.68%, and 2.59% on the ISBI2014 dataset. The classification approach enhanced the accuracy, recall, and specificity by 0.59%, 0.47%, and 1.15% on the Herlev dataset, and by 0.02%, 0.15%, and 0.22% on the SIPaKMed dataset. The experiments demonstrate that the proposed work achieves promising performance on segmentation and classification in cervical cytopathology cell images..
Topics: Female; Humans; Uterine Cervical Neoplasms; Cytology; Cervix Uteri; Papanicolaou Test; Neural Networks, Computer; Image Processing, Computer-Assisted
PubMed: 36744768
DOI: 10.1177/15330338221134833 -
La Clinica Terapeutica Mar 2021One of the increasingly discussed topics in forensic pathology is that concerning the quantification of the postmortem interval (PMI). The estimation of the time...
One of the increasingly discussed topics in forensic pathology is that concerning the quantification of the postmortem interval (PMI). The estimation of the time interval between the death of a person and the discovery of the body is extremely complicated, as it is affected by the influence of many factors, both endogenous and exogenous. With the advancement of knowledge in the field of molecular biology, several studies have been performed, for more than 30 years, on the degradation pattern of macromolecules, such as proteins, DNA, RNA, and the relationship with PMI. Despite initial enthusiasm, studies have shown different kind of limitations in determining PMI in the forensic field. In the last years, consequently, researchers focused their attention on the potential of microRNAs as housekeeping genes, due to their postmortem stability and resistance to degradation. MiRNAs are small, endogenous, single stranded, non-coding RNA molecules identified in plants, animals and DNA virus transcriptome. Various and growing are the fields of application: to establish time of death, to evaluate vitality of skin lesions, in cases of head trauma, and cases of acute myocardial infarction. Their use could also be particularly useful in determining late PMI (beyond 24 hours after death), as no additional markers are available in this scenario. At the moment, scientific research is still at an early stage as it is mainly based on animal models. However, the promising properties of miRNAs and their low cost may make this field of research very interesting for an increasingly precise determination of PMI in the future.
Topics: Animals; Autopsy; Forensic Medicine; Forensic Pathology; Humans; MicroRNAs; Molecular Biology; Postmortem Changes; Real-Time Polymerase Chain Reaction; Time Factors
PubMed: 33763669
DOI: 10.7417/CT.2021.2294 -
Diagnostic Microbiology and Infectious... Oct 2020Robust clinical specimen nucleic acid extraction instrumentation and methods are critical to the performance of downstream molecular diagnostics for the diagnosis of... (Review)
Review
Robust clinical specimen nucleic acid extraction instrumentation and methods are critical to the performance of downstream molecular diagnostics for the diagnosis of drug-resistant tuberculosis (DR-TB). Currently, there is a high level of interest in sequencing-based solutions for rapid and comprehensive DR-TB testing from primary specimens (i.e., sputum). However, there is no standardized or fully automated sputum extraction system that has been widely implemented for use with Mycobacterium tuberculosis complex-containing sputum specimens. For sequencing-based technologies to be widely adopted in clinical laboratory settings in low- and middle-income countries, automated extraction technologies will be important to enhance scalability and reliability and to standardize performance of the downstream assays. Additionally, the ease of automatic technologies allows for faster uptake in laboratories currently without the expertise or infrastructure to perform manual extractions at the same automated throughput. This work is intended to provide an initial specification comparison of available automated DNA extraction systems that could serve as front-end components for existing and future sequencing approaches and provide the framework for future evaluations.
Topics: Automation, Laboratory; DNA, Bacterial; Humans; Mycobacterium tuberculosis; Pathology, Molecular; Reproducibility of Results; Sequence Analysis, DNA; Sputum; Tuberculosis, Multidrug-Resistant
PubMed: 32623232
DOI: 10.1016/j.diagmicrobio.2020.115096 -
Scientific Reports Dec 2023Chlamydophila pneumoniae is a cause of community-acquired pneumonia (CAP) and responsible for 1-2% of cases in paediatric patients. In Mexico, information on this...
Chlamydophila pneumoniae is a cause of community-acquired pneumonia (CAP) and responsible for 1-2% of cases in paediatric patients. In Mexico, information on this microorganism is limited. The aim of this study was to detect C. pneumoniae using two genomic targets in a real-time PCR and IgM/IgG serology assays in paediatric patients with CAP at a tertiary care hospital in Mexico City and to describe their clinical characteristics, radiological features, and outcomes. A total of 154 hospitalized patients with diagnosis of CAP were included. Detection of C. pneumoniae was performed by real-time PCR of the pst and arg genes. Complete blood cell count, C-reactive protein measurement and IgM and IgG detection were performed. Clinical-epidemiological and radiological data from the patients were collected. C. pneumoniae was detected in 25 patients (16%), of whom 88% had underlying disease (P = 0.014). Forty-eight percent of the cases occurred in spring, 36% in girls, and 40% in children older than 6 years. All patients had cough, and 88% had fever. Interstitial pattern on chest-X-ray was the most frequent (68%), consolidation was observed in 32% (P = 0.002). IgM was positive in 7% and IgG in 28.6%. Thirty-six percent presented complications. Four percent died. A high proportion showed co-infection with Mycoplasma pneumoniae (64%). This is the first clinical report of C. pneumoniae as a cause of CAP in Mexican paediatric patients, using two genomic target strategy and serology. We found a frequency of 16.2% with predominance in children under 6 years of age. In addition; cough and fever were the most common symptoms. Early detection of this pathogen allows timely initiation of specific antimicrobial therapy to reduce development of complications. This study is one of the few to describe the presence of C. pneumoniae in patients with underlying diseases.
Topics: Female; Child; Humans; Child, Preschool; Pneumonia, Mycoplasma; Chlamydophila pneumoniae; Pathology, Molecular; Cough; Mexico; Tertiary Care Centers; Mycoplasma pneumoniae; Community-Acquired Infections; Immunoglobulin G; Immunoglobulin M
PubMed: 38052876
DOI: 10.1038/s41598-023-48701-5 -
Thyroid : Official Journal of the... Oct 2022Molecular tests for thyroid nodules with indeterminate fine needle aspiration results are increasingly used in clinical practice; however, true diagnostic summaries of... (Meta-Analysis)
Meta-Analysis Review
Molecular tests for thyroid nodules with indeterminate fine needle aspiration results are increasingly used in clinical practice; however, true diagnostic summaries of these tests are unknown. A systematic review and meta-analysis were completed to (1) evaluate the accuracy of commercially available molecular tests for malignancy in indeterminate thyroid nodules and (2) quantify biases and limitations in studies that validate those tests. PubMed, EMBASE, and Web of Science were systematically searched through July 2021. English language articles that reported original clinical validation attempts of molecular tests for indeterminate thyroid nodules were included if they reported counts of true-negative, true-positive, false-negative, and false-positive results. We performed screening and full-text review, followed by assessment of eight common biases and limitations, extraction of diagnostic and histopathological information, and meta-analysis of clinical validity using a bivariate linear mixed-effects model. Forty-nine studies were included. Meta-analysis of Afirma Gene expression classifiers (GEC; = 38 studies) revealed a sensitivity of 0.92 (confidence interval: 0.90-0.94), specificity of 0.26 (0.20-0.32), negative likelihood ratio (LR-) of 0.32 (0.23-0.44), positive LR+ of 1.24 (1.15-1.35), and area under the curve (AUC) of 0.83 (0.74-0.89). Afirma Genomic Sequencing Classifier (GSC; = 10) had a sensitivity of 0.94 (0.89-0.96), specificity of 0.38 (0.27-0.50), LR- of 0.18 (0.10-0.30), LR+ of 1.52 (1.28-1.87), and AUC of 0.91 (0.62-0.92). ThyroSeq v1 and v2 ( = 10) had a sensitivity of 0.86 (0.82-0.90), specificity of 0.74 (0.59-0.85), LR- of 0.19 (0.13-0.26), LR+ of 3.52 (2.08-5.92), and AUC of 0.86 (0.81-0.90). ThyroSeq v3 ( = 6) had a sensitivity of 0.92 (0.86-0.95), specificity of 0.41 (0.18-0.69), LR- of 0.24 (0.09-0.62), LR+ of 1.67 (1.09-2.98), and AUC of 0.90 (0.63-0.92). Fourteen percent of studies conducted a blinded histopathologic review of excised thyroid nodules, and 8% made the decision to go to surgery blind to molecular test results. Meta-analyses reveal a high diagnostic accuracy of molecular tests for thyroid nodule assessment of malignancy risk; however, these studies are subject to several limitations. Limitations and their potential clinical impacts must be addressed and, when feasible, adjusted for using valid statistical methodologies.
Topics: Humans; Thyroid Nodule; Pathology, Molecular; Biopsy, Fine-Needle; Molecular Diagnostic Techniques; Bias; Thyroid Neoplasms
PubMed: 35999710
DOI: 10.1089/thy.2022.0269 -
Indian Journal of Pathology &... May 2022Over the last three decades, skin punch biopsy has become the gold standard for diagnosis of small fiber neuropathies, including autonomic neuropathies commonly seen in... (Review)
Review
Over the last three decades, skin punch biopsy has become the gold standard for diagnosis of small fiber neuropathies, including autonomic neuropathies commonly seen in diabetics, patients with HIV, and children with hereditary sensory autonomic neuropathies and toxin-induced neuropathy. Clinical, biochemical, electrophysiological tests are inconclusive, making it difficult to diagnose and initiate treatment. A skin punch biopsy is easy to perform in the outpatient clinic, is highly sensitive, and provides an objective diagnosis. Importantly, it helps avoid performing invasive nerve biopsy in patients with small fiber neuropathy, thereby preventing complications such as non-healing of the biopsy site, which is common in these patients. Secondly, the greatest advantage of skin punch biopsies is that they can be repeated any number of times, unlike a nerve biopsy, and are useful to evaluate disease progression and therapeutic response. More recently, its use has been expanded to the diagnosis of large fiber neuropathies, inherited demyelinating neuropathies, etc., obviating the need for a nerve biopsy. The European Federation of Neurological Societies has published guidelines for evaluation to ensure uniformity with regard to the site of biopsy, processing, and quantification. The evaluation of the skin biopsy involves morphometric assessment of the intraepidermal nerve fiber density using PGP 9.5 immunostained sections by bright-field microscopy. This review focuses on the practical aspects of skin punch biopsy and its utility for the practicing pathologist.
Topics: Biopsy; Child; Humans; Nerve Fibers; Neuropathology; Peripheral Nervous System Diseases; Skin; Small Fiber Neuropathy
PubMed: 35562165
DOI: 10.4103/ijpm.ijpm_92_22 -
Thyroid : Official Journal of the... Jan 2024An accurate preoperative workup of cytologically indeterminate thyroid nodules (ITN) may rule out malignancy and avoid diagnostic surgery for benign nodules. This study... (Clinical Trial)
Clinical Trial
An accurate preoperative workup of cytologically indeterminate thyroid nodules (ITN) may rule out malignancy and avoid diagnostic surgery for benign nodules. This study assessed the performance of molecular diagnostics (MD) and 2-[F]fluoro-2-deoxy-d-glucose ([F]FDG)-positron emission tomography/computed tomography (PET/CT) in ITN, including their combined use, and explored whether molecular alterations drive the differences in [F]FDG uptake among benign nodules. Adult, euthyroid patients with a Bethesda III or IV thyroid nodule were prospectively included in this multicenter study. They all underwent MD and an [F]FDG-PET/CT scan of the neck. MD was performed using custom next-generation sequencing panels for somatic mutations, gene fusions, and copy number alterations and loss of heterozygosity. Sensitivity, specificity, negative and positive predictive value (NPV, PPV), and benign call rate (BCR) were assessed for MD and [F]FDG-PET/CT separately and for a combined approach using both techniques. In 115 of the 132 (87%) included patients, MD yielded a diagnostic result on cytology. Sensitivity, specificity, NPV, PPV, and BCR were 80%, 69%, 91%, 48%, and 57% for MD, and 93%, 41%, 95%, 36%, and 32% for [F]FDG-PET/CT, respectively. When combined, sensitivity and specificity were 95% and 44% for a double-negative test (i.e., negative MD plus negative [F]FDG-PET/CT) and 68% and 86% for a double-positive test, respectively. Concordance was 63% (82/130) between MD and [F]FDG-PET/CT. There were more MD-positive nodules among the [F]FDG-positive benign nodules (25/59, 42%, including 11 (44%) isolated RAS mutations) than among the [F]FDG-negative benign nodules (7/30, 19%, = 0.02). In oncocytic ITN, the BCR of [F]FDG-PET/CT was mere 3% and MD was the superior technique. MD and [F]FDG-PET/CT are both accurate rule-out tests when unresected nodules that remain unchanged on ultrasound follow-up are considered benign. It may vary worldwide which test is considered most suitable, depending on local availability of diagnostics, expertise, and cost-effectiveness considerations. Although complementary, the benefits of their combined use may be confined when therapeutic consequences are considered, and should therefore not routinely be recommended. In nononcocytic ITN, sequential testing may be considered in case of a first-step MD negative test to confirm that withholding diagnostic surgery is oncologically safe. In oncocytic ITN, after further validation studies, MD might be considered. This trial is registered with ClinicalTrials.gov: NCT02208544 (August 5, 2014), https://clinicaltrials.gov/ct2/show/NCT02208544.
Topics: Adult; Humans; Fluorodeoxyglucose F18; Pathology, Molecular; Positron Emission Tomography Computed Tomography; Positron-Emission Tomography; Radiopharmaceuticals; Thyroid Neoplasms; Thyroid Nodule
PubMed: 38009209
DOI: 10.1089/thy.2023.0337 -
Romanian Journal of Morphology and... 2020In the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, healthcare workers are at high risk to be infected with this new coronavirus, particularly... (Review)
Review
In the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, healthcare workers are at high risk to be infected with this new coronavirus, particularly when they handle not only patients, but also their body fluids. In Romania, even though the protective measures to be used by medical staff in emergency departments, clinical departments, radiology departments, clinical laboratories and morgues services are well known, there is little information about the protection of medical staff in the laboratories of cytopathology and histopathology. In this article, we will discuss the transmission routes of the new coronavirus, the surfaces it could contaminate in a hospital, as well as the modalities of its inactivation. We will present some guidelines for preparing the pathology departments to face the pandemic situation like the present one. Also, we will point out some possible recommendations/suggestions for protective measures to be taken by laboratory staff during the cytological and histopathological procedures when they manipulate body fluids or surgical samples of patients with suspected or confirmed coronavirus disease 2019 (COVID-19). Laboratory personnel should be aware that any body fluid or surgical specimen that arrives in the laboratory may contain SARS-CoV-2 and, as such, they should act after new working procedures. We recommend restraint from performing extemporaneous examination (smear and frozen section) and cytopathological examination in laboratories that do not have adequate condition for handling and processing Hazard Group 3 (HG3) pathogens, as SARS-CoV-2. Also, laboratory personnel should pay attention to instruments, technical equipment, or environmental surfaces as these also can be contaminated with the new coronavirus.
Topics: COVID-19; Guidelines as Topic; Humans; Infection Control; Infectious Disease Transmission, Patient-to-Professional; Laboratory Personnel; Pandemics; Pathology; Romania; SARS-CoV-2
PubMed: 34171056
DOI: 10.47162/RJME.61.4.09