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Journal of Atherosclerosis and... Jul 2023Advances in immunosuppressive therapy; posttransplant management of allograft rejection; and measures against infectious diseases, cardiovascular diseases, and... (Review)
Review
Advances in immunosuppressive therapy; posttransplant management of allograft rejection; and measures against infectious diseases, cardiovascular diseases, and malignancy dramatically improved graft and patient survival after kidney transplantation (KT). Among them, kidney allograft biopsy is an important tool and the gold standard for the diagnosis of various kidney allograft injuries, including allograft rejection, virus-induced nephropathy, calcineurin inhibitor toxicity, and posttransplant glomerular diseases. The Banff Conference on Allograft Pathology has contributed to establishing the diagnostic criteria for kidney allograft rejection and polyomavirus-associated nephropathy that are used as a common standard worldwide. In addition to the for-cause biopsy, many transplant centers perform protocol biopsies in the early and late posttransplant periods to detect and treat allograft injury earlier. Preimplantation biopsy in deceased-donor KT has also been performed, especially in the marginal donor, and attempts have been made to predict the prognosis in combination with clinical information and the renal resistance of hypothermic machine perfusion. Regarding the preimplantation biopsy from a living kidney donor, it can provide useful information on aging and/or early changes in lifestyle diseases, such as glomerulosclerosis, tubulointerstitial changes, and arterial and arteriolar sclerosis, and be used as a reference for the subsequent management of living donors. In this review, morphologic features of important kidney allograft pathology, such as allograft rejection and polyomavirus-associated nephropathy, according to the latest Banff classification and additional information derived from protocol biopsy, and future perspectives with recently developed technologies are discussed.
Topics: Humans; Kidney Transplantation; Graft Rejection; Transplantation, Homologous; Kidney Diseases; Allografts
PubMed: 37245995
DOI: 10.5551/jat.RV22005 -
Translational Vision Science &... Aug 2023To develop a feline model of acute Acanthamoeba keratitis using methods that replicate natural routes of infection transmission.
PURPOSE
To develop a feline model of acute Acanthamoeba keratitis using methods that replicate natural routes of infection transmission.
METHODS
Corneal Acanthamoeba castellanii inoculation was performed by three methods: topical inoculation with Acanthamoeba solution following corneal abrasion, placement of a contaminated contact lens for 7 days, and placement of a contaminated contact lens for 7 days following corneal abrasion. Sham inoculations with parasite-free medium and sterile contact lenses were also performed. Cats were monitored by ocular examination and in vivo corneal confocal microscopy for 21 days post-inoculation. Corneal samples were collected at intervals for microbiologic assessment, histopathology, and immunohistochemistry.
RESULTS
All cats in the corneal abrasion groups developed clinical keratitis. Clinical ocular disease was inconsistently detected in cats from the contaminated contact lens only group. Initial corneal lesions were characterized by multifocal epithelial leukocyte infiltrates. Ocular lesions progressed to corneal epithelial ulceration and diffuse stromal inflammation. After 14 days, corneal ulcerations resolved, and stromal inflammation consolidated into multifocal subepithelial and stromal infiltrates. Corneal amoebae were detected by culture, in vivo confocal microscopy, histopathology, and immunohistochemistry in cats with keratitis. Neutrophilic and lymphocytic keratoconjunctivitis with lymphoplasmacytic anterior uveitis were identified by histopathology. Coinfection with aerobic bacteria was detected in some, but not all, cats with keratitis. Ocular disease was not detected in the sham inoculation groups.
CONCLUSIONS
Feline Acanthamoeba keratitis is experimentally transmissible by contaminated contact lenses and topical inoculation following corneal epithelial trauma.
TRANSLATIONAL RELEVANCE
Experimentally induced acute Acanthamoeba keratitis in cats is clinically and histopathologically similar to its human counterpart.
Topics: Cats; Animals; Humans; Acanthamoeba Keratitis; Acanthamoeba castellanii; Cornea; Corneal Injuries; Inflammation
PubMed: 37566398
DOI: 10.1167/tvst.12.8.10 -
Neuro-oncology Nov 2023The international, multicenter registry LOGGIC Core BioClinical Data Bank aims to enhance the understanding of tumor biology in pediatric low-grade glioma (pLGG) and...
BACKGROUND
The international, multicenter registry LOGGIC Core BioClinical Data Bank aims to enhance the understanding of tumor biology in pediatric low-grade glioma (pLGG) and provide clinical and molecular data to support treatment decisions and interventional trial participation. Hence, the question arises whether implementation of RNA sequencing (RNA-Seq) using fresh frozen (FrFr) tumor tissue in addition to gene panel and DNA methylation analysis improves diagnostic accuracy and provides additional clinical benefit.
METHODS
Analysis of patients aged 0 to 21 years, enrolled in Germany between April 2019 and February 2021, and for whom FrFr tissue was available. Central reference histopathology, immunohistochemistry, 850k DNA methylation analysis, gene panel sequencing, and RNA-Seq were performed.
RESULTS
FrFr tissue was available in 178/379 enrolled cases. RNA-Seq was performed on 125 of these samples. We confirmed KIAA1549::BRAF-fusion (n = 71), BRAF V600E-mutation (n = 12), and alterations in FGFR1 (n = 14) as the most frequent alterations, among other common molecular drivers (n = 12). N = 16 cases (13%) presented rare gene fusions (eg, TPM3::NTRK1, EWSR1::VGLL1, SH3PXD2A::HTRA1, PDGFB::LRP1, GOPC::ROS1). In n = 27 cases (22%), RNA-Seq detected a driver alteration not otherwise identified (22/27 actionable). The rate of driver alteration detection was hereby increased from 75% to 97%. Furthermore, FGFR1 internal tandem duplications (n = 6) were only detected by RNA-Seq using current bioinformatics pipelines, leading to a change in analysis protocols.
CONCLUSIONS
The addition of RNA-Seq to current diagnostic methods improves diagnostic accuracy, making precision oncology treatments (MEKi/RAFi/ERKi/NTRKi/FGFRi/ROSi) more accessible. We propose to include RNA-Seq as part of routine diagnostics for all pLGG patients, especially when no common pLGG alteration was identified.
Topics: Child; Humans; Proto-Oncogene Proteins B-raf; Pathology, Molecular; Protein-Tyrosine Kinases; RNA-Seq; Proto-Oncogene Proteins; Precision Medicine; Glioma; DNA-Binding Proteins; Transcription Factors
PubMed: 37075810
DOI: 10.1093/neuonc/noad078 -
Multimedia Manual of Cardiothoracic... May 2024Bone metastasis is the most common form of distant metastasis encountered within the breast cancer population. Surgical resection of bone metastases is a curative...
Bone metastasis is the most common form of distant metastasis encountered within the breast cancer population. Surgical resection of bone metastases is a curative treatment option in patients who present with an isolated solitary lesion and no other associated disease. This decision is typically made following a multidisciplinary discussion. Patients can also be put forward for surgical excision of bone metastases following inadequate response to chemotherapy or radiotherapy. With tumours located in the manubrium of the sternum, surgery serves not only to resect the bone metastasis but to provide suitable chest wall reconstruction. The goal of this approach is to maintain the structural and bony stability of the chest wall as well as that of associated structures, e.g. rib insertion or articulation of the shoulder girdle. A widely utilized approach involves excising the area of metastasis within the manubrium followed by implanting a bone cement prosthesis. Titanium plates are used to fix the bone prosthesis to the sternal body inferiorly and to the remainder of the manubrium superiorly. We present a step-by-step video tutorial for performing a lower hemi-manubriectomy in a patient with triple-negative breast cancer. Our goal is to describe the fundamental principles and surgical techniques used to perform this procedure followed by the postoperative outcomes.
Topics: Humans; Female; Bone Neoplasms; Manubrium; Triple Negative Breast Neoplasms; Middle Aged
PubMed: 38690721
DOI: 10.1510/mmcts.2024.005 -
Indian Journal of Nephrology 2023Renal allograft rejection contributes to significant morbidity and graft loss. In this setting, early detection of rejection is of paramount importance, which currently...
BACKGROUND
Renal allograft rejection contributes to significant morbidity and graft loss. In this setting, early detection of rejection is of paramount importance, which currently relies on histopathology. A reliable non-invasive marker to predict rejection would make surveillance and decision-making easier. Donor-derived cell-free DNA (dd-Cf-DNA) has recently been reported as an emerging tool to predict rejection noninvasively. The utility of cell-free DNA in clinical practice has so far not been studied in an Indian setting. As it offers direct clinical application, we have chosen to investigate this biomarker as a tool to predict rejection.
MATERIALS AND METHODS
A pilot study with convenient sample size was designed, as this is the first of its kind study so far reported from India. Patients being evaluated with a graft biopsy for graft dysfunction were included. Patients with stable graft function, defined as creatinine within 10% of their best creatinine and no proteinuria for the preceding 12 months, were also included. Ten milliliters of whole blood from each of the recipients was collected in DNA isolation tubes. Two milliliters of donor blood was also obtained in ethylenediaminetetraacetic acid (EDTA) tubes. All recipients also provided a buccal swab. Total cell-free DNA was extracted from 2 ml of recipient plasma using circulating DNA isolation kit. Upon identification of the donor-specific DNA marker for each of the patients from the paired donor sample, presence of the cell-free DNA fraction in the recipient's plasma was detected and quantified. Renal biopsy reports and clinical details were also recorded. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were analyzed. Receiver operating characteristic (ROC) curve analysis was also performed.
RESULTS
A total of 31 patients were recruited. Twenty patients underwent graft biopsies for graft dysfunction, of which 12 patients had features of active rejection and eight had nonrejection causes of graft dysfunction. Eleven patients with stable graft were included in the study. In our study, dd-Cf-DNA performed best in predicting antibody-mediated rejection (ABMR) and higher grades of T-cell-mediated rejection (TCMR) (1B). It did not detect TCMR 1A accurately. It serves as a good marker to rule out rejection. It gave a NPV of 100% for TCMR 1B or ABMR, 100% for ABMR alone, and 81% for any rejection. dd-Cf-DNA percentages outperform absolute concentrations in their discriminatory ability.
CONCLUSION
We have demonstrated the diagnostic accuracy of dd-Cf-DNA in predicting active rejection of the renal allograft. It performs well in ABMR and higher grades of TCMR. This is the first of its kind study reported from India, to the best of our knowledge. This tool serves as a good rule out test for ABMR and higher grades of TCMR. It performs poorly in TCMR 1A.
PubMed: 37781552
DOI: 10.4103/ijn.ijn_152_22 -
American Journal of Physiology. Lung... Oct 2023Bronchopulmonary dysplasia (BPD) is a disease of prematurity related to the arrest of normal lung development. The objective of this study was to better understand how...
Bronchopulmonary dysplasia (BPD) is a disease of prematurity related to the arrest of normal lung development. The objective of this study was to better understand how proteome modulation and cell-type shifts are noted in BPD pathology. Pediatric human donors aged 1-3 yr were classified based on history of prematurity and histopathology consistent with "healed" BPD (hBPD, = 3) and "established" BPD (eBPD, = 3) compared with respective full-term born ( = 6) age-matched term controls. Proteins were quantified by tandem mass spectroscopy with selected Western blot validations. Multiplexed immunofluorescence (MxIF) microscopy was performed on lung sections to enumerate cell types. Protein abundances and MxIF cell frequencies were compared among groups using ANOVA. Cell type and ontology enrichment were performed using an in-house tool and/or EnrichR. Proteomics detected 5,746 unique proteins, 186 upregulated and 534 downregulated, in eBPD versus control with fewer proteins differentially abundant in hBPD as compared with age-matched term controls. Cell-type enrichment suggested a loss of alveolar type I, alveolar type II, endothelial/capillary, and lymphatics, and an increase in smooth muscle and fibroblasts consistent with MxIF. Histochemistry and Western analysis also supported predictions of upregulated ferroptosis in eBPD versus control. Finally, several extracellular matrix components mapping to angiogenesis signaling pathways were altered in eBPD. Despite clear parsing by protein abundance, comparative MxIF analysis confirms phenotypic variability in BPD. This work provides the first demonstration of tandem mass spectrometry and multiplexed molecular analysis of human lung tissue for critical elucidation of BPD trajectory-defining factors into early childhood. We provide new insights into the natural history of bronchopulmonary dysplasia in donor human lungs after the neonatal intensive care unit hospitalization. This study provides new insights into how the proteome and histopathology of BPD changes in early childhood, uncovering novel pathways for future study.
Topics: Child, Preschool; Infant, Newborn; Humans; Child; Bronchopulmonary Dysplasia; Immunohistochemistry; Proteome; Proteomics; Lung
PubMed: 37489262
DOI: 10.1152/ajplung.00130.2023 -
European Spine Journal : Official... Nov 2023Low back pain is the leading contributor to disability burden globally. It is commonly due to degeneration of the lumbar intervertebral discs (LDD). Magnetic resonance... (Meta-Analysis)
Meta-Analysis Review
Are current machine learning applications comparable to radiologist classification of degenerate and herniated discs and Modic change? A systematic review and meta-analysis.
INTRODUCTION
Low back pain is the leading contributor to disability burden globally. It is commonly due to degeneration of the lumbar intervertebral discs (LDD). Magnetic resonance imaging (MRI) is the current best tool to visualize and diagnose LDD, but places high time demands on clinical radiologists. Automated reading of spine MRIs could improve speed, accuracy, reliability and cost effectiveness in radiology departments. The aim of this review and meta-analysis was to determine if current machine learning algorithms perform well identifying disc degeneration, herniation, bulge and Modic change compared to radiologists.
METHODS
A PRISMA systematic review protocol was developed and four electronic databases and reference lists were searched. Strict inclusion and exclusion criteria were defined. A PROBAST risk of bias and applicability analysis was performed.
RESULTS
1350 articles were extracted. Duplicates were removed and title and abstract searching identified original research articles that used machine learning (ML) algorithms to identify disc degeneration, herniation, bulge and Modic change from MRIs. 27 studies were included in the review; 25 and 14 studies were included multi-variate and bivariate meta-analysis, respectively. Studies used machine learning algorithms to assess LDD, disc herniation, bulge and Modic change. Models using deep learning, support vector machine, k-nearest neighbors, random forest and naïve Bayes algorithms were included. Meta-analyses found no differences in algorithm or classification performance. When algorithms were tested in replication or external validation studies, they did not perform as well as when assessed in developmental studies. Data augmentation improved algorithm performance when compared to models used with smaller datasets, there were no performance differences between augmented data and large datasets.
DISCUSSION
This review highlights several shortcomings of current approaches, including few validation attempts or use of large sample sizes. To the best of the authors' knowledge, this is the first systematic review to explore this topic. We suggest the utilization of deep learning coupled with semi- or unsupervised learning approaches. Use of all information contained in MRI data will improve accuracy. Clear and complete reporting of study design, statistics and results will improve the reliability and quality of published literature.
Topics: Humans; Intervertebral Disc Displacement; Intervertebral Disc Degeneration; Bayes Theorem; Reproducibility of Results; Lumbar Vertebrae; Systematic Reviews as Topic; Magnetic Resonance Imaging; Radiologists
PubMed: 37150769
DOI: 10.1007/s00586-023-07718-0 -
PLoS Pathogens Aug 2023Most humans have a lifelong imperceptible BK Polyomavirus (BKPyV) infection in epithelial cells lining the reno-urinary tract. In kidney transplant recipients,...
Most humans have a lifelong imperceptible BK Polyomavirus (BKPyV) infection in epithelial cells lining the reno-urinary tract. In kidney transplant recipients, unrestricted high-level replication of donor-derived BKPyV in the allograft underlies polyomavirus-associated nephropathy, a condition with massive epithelial cell loss and inflammation causing premature allograft failure. There is limited understanding on how BKPyV disseminates throughout the reno-urinary tract and sometimes causes kidney damage. Tubule epithelial cells are tightly connected and have unique apical and basolateral membrane domains with highly specialized functions but all in vitro BKPyV studies have been performed in non-polarized cells. We therefore generated a polarized cell model of primary renal proximal tubule epithelial cells (RPTECs) and characterized BKPyV entry and release. After 8 days on permeable inserts, RPTECs demonstrated apico-basal polarity. BKPyV entry was most efficient via the apical membrane, that in vivo faces the tubular lumen, and depended on sialic acids. Progeny release started between 48 and 58 hours post-infection (hpi), and was exclusively detected in the apical compartment. From 72 hpi, cell lysis and detachment gradually increased but cells were mainly shed by extrusion and the barrier function was therefore maintained. The decoy-like cells were BKPyV infected and could transmit BKPyV to uninfected cells. By 120 hpi, the epithelial barrier was disrupted by severe cytopathic effects, and BKPyV entered the basolateral compartment mimicking the interstitial space. Addition of BKPyV-specific neutralizing antibodies to this compartment inhibited new infections. Taken together, we propose that during in vivo low-level BKPyV replication, BKPyV disseminates inside the tubular system, thereby causing minimal damage and delaying immune detection. However, in kidney transplant recipients lacking a well-functioning immune system, replication in the allograft will progress and eventually cause denudation of the basement membrane, leading to an increased number of decoy cells, high-level BKPyV-DNAuria and DNAemia, the latter a marker of allograft damage.
Topics: Humans; Cytology; BK Virus; Polyomavirus; Kidney; Epithelial Cells; Polyomavirus Infections
PubMed: 37639485
DOI: 10.1371/journal.ppat.1011622 -
Cancer Biomarkers : Section a of... 2024Breast cancer is one of the leading causes of death in women worldwide. Histopathology analysis of breast tissue is an essential tool for diagnosing and staging breast... (Review)
Review
BACKGROUND
Breast cancer is one of the leading causes of death in women worldwide. Histopathology analysis of breast tissue is an essential tool for diagnosing and staging breast cancer. In recent years, there has been a significant increase in research exploring the use of deep-learning approaches for breast cancer detection from histopathology images.
OBJECTIVE
To provide an overview of the current state-of-the-art technologies in automated breast cancer detection in histopathology images using deep learning techniques.
METHODS
This review focuses on the use of deep learning algorithms for the detection and classification of breast cancer from histopathology images. We provide an overview of publicly available histopathology image datasets for breast cancer detection. We also highlight the strengths and weaknesses of these architectures and their performance on different histopathology image datasets. Finally, we discuss the challenges associated with using deep learning techniques for breast cancer detection, including the need for large and diverse datasets and the interpretability of deep learning models.
RESULTS
Deep learning techniques have shown great promise in accurately detecting and classifying breast cancer from histopathology images. Although the accuracy levels vary depending on the specific data set, image pre-processing techniques, and deep learning architecture used, these results highlight the potential of deep learning algorithms in improving the accuracy and efficiency of breast cancer detection from histopathology images.
CONCLUSION
This review has presented a thorough account of the current state-of-the-art techniques for detecting breast cancer using histopathology images. The integration of machine learning and deep learning algorithms has demonstrated promising results in accurately identifying breast cancer from histopathology images. The insights gathered from this review can act as a valuable reference for researchers in this field who are developing diagnostic strategies using histopathology images. Overall, the objective of this review is to spark interest among scholars in this complex field and acquaint them with cutting-edge technologies in breast cancer detection using histopathology images.
Topics: Humans; Breast Neoplasms; Deep Learning; Female; Image Processing, Computer-Assisted; Algorithms; Image Interpretation, Computer-Assisted
PubMed: 38517775
DOI: 10.3233/CBM-230251 -
Diagnostics (Basel, Switzerland) Oct 2023Micro-computed tomography (micro-CT) is a relatively new imaging modality and the three-dimensional (3D) images obtained via micro-CT allow researchers to collect both... (Review)
Review
Micro-computed tomography (micro-CT) is a relatively new imaging modality and the three-dimensional (3D) images obtained via micro-CT allow researchers to collect both quantitative and qualitative information on various types of samples. Micro-CT could potentially be used to examine human diseases and several studies have been published on this topic in the last decade. In this study, the potential uses of micro-CT in understanding and evaluating lung carcinoma and the relevant studies conducted on lung and other tumors are summarized. Currently, the resolution of benchtop laboratory micro-CT units has not reached the levels that can be obtained with light microscopy, and it is not possible to detect the histopathological features (e.g., tumor type, adenocarcinoma pattern, spread through air spaces) required for lung cancer management. However, its ability to provide 3D images in any plane of section, without disturbing the integrity of the specimen, suggests that it can be used as an auxiliary technique, especially in surgical margin examination, the evaluation of tumor invasion in the entire specimen, and calculation of primary and metastatic tumor volume. Along with future developments in micro-CT technology, it can be expected that the image resolution will gradually improve, the examination time will decrease, and the relevant software will be more user friendly. As a result of these developments, micro-CT may enter pathology laboratories as an auxiliary method in the pathological evaluation of lung tumors. However, the safety, performance, and cost effectiveness of micro-CT in the areas of possible clinical application should be investigated. If micro-CT passes all these tests, it may lead to the convergence of radiology and pathology applications performed independently in separate units today, and the birth of a new type of diagnostician who has equal knowledge of the histological and radiological features of tumors.
PubMed: 37892083
DOI: 10.3390/diagnostics13203262