-
Medicine, Science, and the Law Oct 2021Casper's sign refers to the absence of external signs of trauma despite severe and often lethal internal injuries. It occurs because the elasticity and resilience of the...
Casper's sign refers to the absence of external signs of trauma despite severe and often lethal internal injuries. It occurs because the elasticity and resilience of the skin results in it deforming and moving rather than sustaining injuries from being tethered and relatively immobile. Given the known increase in skin and soft-tissue fragility in the elderly with a greater vulnerability for bruising and skin tears, a study was undertaken to determine whether Casper's sign may be present or not in older populations. A review of autopsy files at Forensic Science SA over a 20-year period from January 2000 to December 2019 was performed in individuals ≥80 years of age where death involved blunt chest trauma, blunt abdominal trauma or multiple blunt-force injuries. Four cases were identified. All of the decedents were males aged 82-89 years (=86 years) with deaths associated with a fall (=1) and vehicle impacts (=3). Despite significant and often lethal internal chest/abdominal injuries, none of the cases had external injuries to their torsos. Thus, as Casper's sign may be present at all ages, the absence of external injury in the elderly may be no reflection of the force of the impact or the degree of resultant skeletal and/or internal organ disruption. This may be pertinent in cases of elder abuse.
Topics: Aged, 80 and over; Humans; Male; Autopsy; Forensic Pathology; Skin; Thoracic Injuries; Wounds, Nonpenetrating; Elder Abuse
PubMed: 34018856
DOI: 10.1177/00258024211015096 -
Histopathology Jul 2020We discuss the role of the pathologist for MRI-targeted prostate biopsy with a focus on specimen processing, reporting of pathological findings and quality assurance in... (Review)
Review
We discuss the role of the pathologist for MRI-targeted prostate biopsy with a focus on specimen processing, reporting of pathological findings and quality assurance in establishing a successful MRI-targeted biopsy programme. The authors discuss the current issues relevant to pathologists regarding MRI-targeted prostate biopsy. In addition, a brief review of the recently published literature was performed using an English literature search on PubMed with a focus on original investigations related to MRI-targeted prostate biopsy. Our search terms included the following: 'prostate cancer', 'pathology', 'histology', 'reporting', 'cores', 'imaging', 'MRI' and 'mpMRI'. Prostate multiparametric magnetic resonance imaging (mp-MRI) and MRI-targeted biopsy has been shown to improve the diagnosis of clinically significant prostatic adenocarcinoma and can affect the management of patients with prostate cancer. The current active surveillance guidelines were based on data from TRUS biopsies and not MRI-targeted biopsies. MRI-targeted biopsy acquires multiple cores of tissue from one or more suspicious lesions found on mp-MRI. The way in which multiple targeted core biopsies obtained from a single image-directed region of interest are analysed and reported can potentially alter the Gleason score and tumour burden as reported on biopsy, which could undoubtedly alter patient management. Pathologists play an important role in the reporting of MRI-targeted prostate biopsies. How we report prostate cancer grade and extent on these biopsies can influence patient management. In addition, the pathologist should be involved in the quality assurance for patients undergoing MRI-targeted prostate biopsy.
Topics: Humans; Image-Guided Biopsy; Magnetic Resonance Imaging; Male; Pathologists; Pathology; Prostatic Neoplasms; Specimen Handling
PubMed: 32278319
DOI: 10.1111/his.14113 -
Military Medical Research Mar 2022Traditional diagnostic strategies for infectious disease detection require benchtop instruments that are inappropriate for point-of-care testing (POCT). Emerging... (Review)
Review
Traditional diagnostic strategies for infectious disease detection require benchtop instruments that are inappropriate for point-of-care testing (POCT). Emerging microfluidics, a highly miniaturized, automatic, and integrated technology, are a potential substitute for traditional methods in performing rapid, low-cost, accurate, and on-site diagnoses. Molecular diagnostics are widely used in microfluidic devices as the most effective approaches for pathogen detection. This review summarizes the latest advances in microfluidics-based molecular diagnostics for infectious diseases from academic perspectives and industrial outlooks. First, we introduce the typical on-chip nucleic acid processes, including sample preprocessing, amplification, and signal read-out. Then, four categories of microfluidic platforms are compared with respect to features, merits, and demerits. We further discuss application of the digital assay in absolute nucleic acid quantification. Both the classic and recent microfluidics-based commercial molecular diagnostic devices are summarized as proof of the current market status. Finally, we propose future directions for microfluidics-based infectious disease diagnosis.
Topics: Communicable Diseases; Humans; Lab-On-A-Chip Devices; Microfluidic Analytical Techniques; Microfluidics; Pathology, Molecular
PubMed: 35300739
DOI: 10.1186/s40779-022-00374-3 -
Nature Medicine May 2021Machine learning techniques have great potential to improve medical diagnostics, offering ways to improve accuracy, reproducibility and speed, and to ease workloads for... (Review)
Review
Machine learning techniques have great potential to improve medical diagnostics, offering ways to improve accuracy, reproducibility and speed, and to ease workloads for clinicians. In the field of histopathology, deep learning algorithms have been developed that perform similarly to trained pathologists for tasks such as tumor detection and grading. However, despite these promising results, very few algorithms have reached clinical implementation, challenging the balance between hope and hype for these new techniques. This Review provides an overview of the current state of the field, as well as describing the challenges that still need to be addressed before artificial intelligence in histopathology can achieve clinical value.
Topics: Algorithms; Deep Learning; Humans; Pathology, Molecular; Precision Medicine
PubMed: 33990804
DOI: 10.1038/s41591-021-01343-4 -
Current Opinion in Oncology May 2021Pathology is the cornerstone of cancer care. Pathomics, which represents the use of artificial intelligence in digital pathology, is an emerging and promising field that... (Review)
Review
PURPOSE OF REVIEW
Pathology is the cornerstone of cancer care. Pathomics, which represents the use of artificial intelligence in digital pathology, is an emerging and promising field that will revolutionize medical and surgical pathology in the coming years. This review provides an overview of pathomics, its current and future applications and its most relevant applications in Head and Neck cancer care.
RECENT FINDINGS
The number of studies investigating the use of artificial intelligence in pathology is rapidly growing, especially as the utilization of deep learning has shown great potential with Whole Slide Images. Even though numerous steps still remain before its clinical use, Pathomics has been used for varied applications comprising of computer-assisted diagnosis, molecular anomalies prediction, tumor microenvironment and biomarker identification as well as prognosis evaluation. The majority of studies were performed on the most frequent cancers, notably breast, prostate, and lung. Interesting results were also found in Head and Neck cancers.
SUMMARY
Even if its use in Head and Neck cancer care is still low, Pathomics is a powerful tool to improve diagnosis, identify prognostic factors and new biomarkers. Important challenges lie ahead before its use in a clinical practice, notably the lack of information on how AI makes its decisions, the slow deployment of digital pathology, and the need for extensively validated data in order to obtain authorities approval. Regardless, pathomics will most likely improve pathology in general, including Head and Neck cancer care in the coming years.
Topics: Artificial Intelligence; Biomarkers, Tumor; Head and Neck Neoplasms; Humans; Image Processing, Computer-Assisted; Pathology; Tumor Microenvironment
PubMed: 33782358
DOI: 10.1097/CCO.0000000000000731 -
Nature Reviews. Genetics Nov 2021Synthetic biology seeks to redesign biological systems to perform novel functions in a predictable manner. Recent advances in bacterial and mammalian cell engineering... (Review)
Review
Synthetic biology seeks to redesign biological systems to perform novel functions in a predictable manner. Recent advances in bacterial and mammalian cell engineering include the development of cells that function in biological samples or within the body as minimally invasive diagnostics or theranostics for the real-time regulation of complex diseased states. Ex vivo and in vivo cell-based biosensors and therapeutics have been developed to target a wide range of diseases including cancer, microbiome dysbiosis and autoimmune and metabolic diseases. While probiotic therapies have advanced to clinical trials, chimeric antigen receptor (CAR) T cell therapies have received regulatory approval, exemplifying the clinical potential of cellular therapies. This Review discusses preclinical and clinical applications of bacterial and mammalian sensing and drug delivery platforms as well as the underlying biological designs that could enable new classes of cell diagnostics and therapeutics. Additionally, we describe challenges that must be overcome for more rapid and safer clinical use of engineered systems.
Topics: Animals; Bacteria; Cell- and Tissue-Based Therapy; Cell-Free System; Humans; Immunomodulation; Mammals; Microbiota; Neoplasms; Pathology, Molecular; Receptors, Antigen, T-Cell; Receptors, Chimeric Antigen; Synthetic Biology; T-Lymphocytes
PubMed: 34234299
DOI: 10.1038/s41576-021-00383-3 -
Journal of Neuropathology and... Dec 2022The literature regarding the neuropathological findings in cases of SARS-CoV-2 infection, which causes coronavirus disease 2019 (COVID-19), is expanding. We identified...
The literature regarding the neuropathological findings in cases of SARS-CoV-2 infection, which causes coronavirus disease 2019 (COVID-19), is expanding. We identified 72 patients who died of COVID-19 (n = 48) or had recovered shortly before death (n = 24) and had autopsies performed at our institution (49 males, 23 females; median age at death 76.4 years, range: 0.0-95.0 years). Droplet digital polymerase chain reaction (ddPCR) for the detection of SARS-CoV-2 was performed (n = 58) in multiple brain regions. In cases the assay was successfully completed (n = 50), 98.0% were negative (n = 49) and 2% were indeterminate (n = 1). Most histologic findings were typical of the patient age demographic, such as neurodegenerative disease and arteriolosclerosis. A subset of cases demonstrated findings which may be associated with sequelae of critical illness. We identified 3 cases with destructive perivascular lesions with axonal injury, one of which also harbored perivascular demyelinating lesions. These rare cases may represent a parainfectious process versus sequelae of vascular injury. The lack of detectable SARS-CoV-2 by ddPCR or significant histologic evidence of direct infection suggests that active encephalitis is not a feature of COVID-19.
Topics: Male; Female; Humans; Infant, Newborn; Infant; Child, Preschool; Child; Adolescent; Young Adult; Adult; Middle Aged; Aged; Aged, 80 and over; COVID-19; SARS-CoV-2; Autopsy; Neurodegenerative Diseases; Neuropathology
PubMed: 36355625
DOI: 10.1093/jnen/nlac101 -
JAMA Pediatrics Nov 2023Currently, the diagnostic yield of exome sequencing (ES) and chromosomal microarray analysis (CMA) for short stature cohorts is uncertain. Despite previous studies...
IMPORTANCE
Currently, the diagnostic yield of exome sequencing (ES) and chromosomal microarray analysis (CMA) for short stature cohorts is uncertain. Despite previous studies reporting the widespread use of ES and CMA, a definitive diagnostic yield has not been established.
OBJECTIVE
To investigate the diagnostic yield of ES and CMA in short stature.
DATA SOURCES
A systematic literature search was conducted using relevant keywords in 3 databases (PubMed, Embase, and Web of Science) in February 2023.
STUDY SELECTION
Eligible studies for meta-analysis were those that had at least 10 participants with short stature who were diagnosed using either ES or CMA and the number of diagnosed patients was reported. Of 5222 identified studies, 20 were eventually included in the study.
DATA EXTRACTION AND SYNTHESIS
Two independent investigators extracted relevant information from each study, which was then synthesized using proportional meta-analysis to obtain the overall diagnostic yield of ES and CMA.
MAIN OUTCOMES AND MEASURES
The primary outcome measure was to determine the overall diagnostic yield of ES and CMA. A subgroup meta-analysis was also performed to assess if the diagnostic yield varied depending on whether ES was used as a first-tier or last-resort test. Additionally, a meta-regression was carried out to investigate how the diagnostic yield varied over time.
RESULTS
Twenty studies were included, comprising 1350 patients with short stature who underwent ES and 1070 patients who completed CMA. The overall diagnostic yield of ES among the cohorts and CMA among the cohorts was found to be 27.1% (95% CI, 18.1%-37.2%) and 13.6% (95% CI, 9.2%-18.7%), respectively. No statistically significant difference was observed between the first-tier (27.8%; 95% CI, 15.7%-41.8%) and last-resort groups (25.6%; 95% CI, 13.6%-39.6%) (P = .83) or in the percentage of positively diagnosed patients over time. No statistically significant difference was observed between the first-tier (27.8%; 95% CI, 15.7%-41.8%) and last-resort groups (25.6%; 95% CI, 13.6%-39.6%) (P = .83) or in the percentage of positively diagnosed patients over time.
CONCLUSION AND RELEVANCE
This systematic review and meta-analysis provides high-level evidence supporting the diagnostic efficacy of ES and CMA in patients with short stature. The findings serve as a solid reference for clinicians when making informed decisions about recommending these genetic tests.
Topics: Humans; Exome Sequencing; Pathology, Molecular; Genetic Testing; Microarray Analysis
PubMed: 37695591
DOI: 10.1001/jamapediatrics.2023.3566 -
Forensic Science International Jan 2022Identification by STR analysis of bones is time-consuming, mainly due to the lengthy decalcification required and complex DNA extraction process. To streamline this...
Identification by STR analysis of bones is time-consuming, mainly due to the lengthy decalcification required and complex DNA extraction process. To streamline this process, we developed a direct STR typing protocol from bone samples. We optimized bone sample amounts using femur and tibia and two commercial PCR kits (Identifiler™ Plus and IDplex Plus kits). Optimally, 100 mg of bone powder in 300 µL PBS buffer was heated at 98 °C for three minutes to produce a supernatant for DNA amplification. IDplex Plus performed better than Identifiler™ Plus in terms of allele recovery and peak height. Fifteen samples of each of seven bone elements (1st distal phalange of hand, capitate, femur, metacarpal 4, patella, talus, and tibia; N = 105) were then subjected to direct STR typing with the optimized protocol, and 94.3% were high partial to full profiles. The performance of the developed protocol was similar for all bone elements. Median peak heights were significantly better in profiles of cancellous bone than compact bone (p = 0.033) and significantly different across the bone elements (p < 0.001). Ten casework samples from various conditions and up to 7-year-PMI were subjected to both direct STR and conventional STR typing. No significant difference in the number of alleles was seen (95% HDI of -13.5 to 5.15). As well as being rapid, convenient, and safe, the protocol could help improve STR typing from bones.
Topics: DNA; DNA Fingerprinting; Forensic Pathology; Humans; Microsatellite Repeats; Patella; Polymerase Chain Reaction
PubMed: 34794063
DOI: 10.1016/j.forsciint.2021.111099 -
EMBO Molecular Medicine May 2023Several promising plasma biomarkers for Alzheimer's disease have been recently developed, but their neuropathological correlates have not yet been fully determined. To...
Several promising plasma biomarkers for Alzheimer's disease have been recently developed, but their neuropathological correlates have not yet been fully determined. To investigate and compare independent associations between multiple plasma biomarkers (p-tau181, p-tau217, p-tau231, Aβ42/40, GFAP, and NfL) and neuropathologic measures of amyloid and tau, we included 105 participants from the Arizona Study of Aging and Neurodegenerative Disorders (AZSAND) with antemortem plasma samples and a postmortem neuropathological exam, 48 of whom had longitudinal p-tau217 and p-tau181. When simultaneously including plaque and tangle loads, the Aβ42/40 ratio and p-tau231 were only associated with plaques (ρ [95%CI] = -0.53[-0.65, -0.35], ρ [95%CI] = 0.28[0.10, 0.43]), GFAP was only associated with tangles (ρ [95%CI] = 0.39[0.17, 0.57]), and p-tau217 and p-tau181 were associated with both plaques (ρ [95%CI] = 0.40[0.21, 0.56], ρ [95%CI] = 0.36[0.15, 0.50]) and tangles (ρ [95%CI] = 0.52[0.34, 0.66]; ρ [95%CI] = 0.36[0.17, 0.52]). A model combining p-tau217 and the Aβ42/40 ratio showed the highest accuracy for predicting the presence of Alzheimer's disease neuropathological change (ADNC, AUC[95%CI] = 0.89[0.82, 0.96]) and plaque load (R = 0.55), while p-tau217 alone was optimal for predicting tangle load (R = 0.45). Our results suggest that high-performing assays of plasma p-tau217 and Aβ42/40 might be an optimal combination to assess Alzheimer's-related pathology in vivo.
Topics: Humans; Plaque, Amyloid; Alzheimer Disease; Autopsy; Neuropathology; Biomarkers; tau Proteins; Amyloid beta-Peptides
PubMed: 36912178
DOI: 10.15252/emmm.202217123