ABSTRACT
Pathologists' assessment of sentinel lymph nodes (SNs) for breast cancer (BC) metastases is a treatment-guiding yet labor-intensive and costly task because of the performance of immunohistochemistry (IHC) in morphologically negative cases. This non-randomized, single-center clinical trial (International Standard Randomized Controlled Trial Number:14323711) assessed the efficacy of an artificial intelligence (AI)-assisted workflow for detecting BC metastases in SNs while maintaining diagnostic safety standards. From September 2022 to May 2023, 190 SN specimens were consecutively enrolled and allocated biweekly to the intervention arm (n = 100) or control arm (n = 90). In both arms, digital whole-slide images of hematoxylin-eosin sections of SN specimens were assessed by an expert pathologist, who was assisted by the 'Metastasis Detection' app (Visiopharm) in the intervention arm. Our primary endpoint showed a significantly reduced adjusted relative risk of IHC use (0.680, 95% confidence interval: 0.347-0.878) for AI-assisted pathologists, with subsequent cost savings of ~3,000 . Secondary endpoints showed significant time reductions and up to 30% improved sensitivity for AI-assisted pathologists. This trial demonstrates the safety and potential for cost and time savings of AI assistance.
Subject(s)
Artificial Intelligence , Breast Neoplasms , Lymphatic Metastasis , Sentinel Lymph Node , Humans , Breast Neoplasms/pathology , Breast Neoplasms/diagnosis , Female , Sentinel Lymph Node/pathology , Lymphatic Metastasis/diagnosis , Middle Aged , Sentinel Lymph Node Biopsy/methods , Adult , Aged , Immunohistochemistry/methodsABSTRACT
AIMS: Oxaliplatin is an important chemotherapeutic agent, used in the treatment of hepatic colorectal metastases, and known to induce the sinusoidal obstruction syndrome (SOS). Pathophysiological knowledge concerning SOS is based on a rat model. Therefore, the aim was to perform a comprehensive study of the features of human SOS, using both light microscopy (LM) and electron microscopy (EM). METHODS AND RESULTS: Included were all patients of whom wedge liver biopsies were collected during a partial hepatectomy for colorectal liver metastases, in a 4-year period. The wedge biopsy were perfusion fixated and processed for LM and EM. The SOS lesions were selected by LM and details were studied using EM. Material was available of 30 patients, of whom 28 patients received neo-adjuvant oxaliplatin. Eighteen (64%) of the 28 patients showed SOS lesions, based on microscopy. The lesions consisted of sinusoidal endothelial cell detachment from the space of Disse on EM. In the enlarged space of Disse a variable amount of erythrocytes were located. CONCLUSION: Sinusoidal endothelial cell detachment was present in human SOS, accompanied by enlargement of the space of Disse and erythrocytes in this area. These findings, originally described in a rat model, were now for the first time confirmed in human livers under clinically relevant settings.
Subject(s)
Hepatic Veno-Occlusive Disease/pathology , Liver/pathology , Liver/ultrastructure , Aged , Antineoplastic Agents/therapeutic use , Biopsy , Capillaries/cytology , Capillaries/ultrastructure , Chemotherapy, Adjuvant , Colorectal Neoplasms/pathology , Endothelium/ultrastructure , Hepatectomy , Humans , Liver Neoplasms/drug therapy , Liver Neoplasms/surgery , Male , Microscopy, Electron/methods , Microscopy, Polarization/methods , Middle Aged , Neoadjuvant Therapy , Organoplatinum Compounds/therapeutic use , OxaliplatinABSTRACT
BACKGROUND: Oxaliplatin is used as a neo-adjuvant therapy in hepatic colorectal carcinoma metastasis. This treatment has significant side effects, as oxaliplatin is toxic to the sinusoidal endothelial cells and can induce sinusoidal obstruction syndrome (SOS), which is related to decreased overall survival. Glutathione has an important role in the defence system, catalysed by glutathione S-transferase (GST), including two non-enzyme producing polymorphisms (GSTM1-null and GSTT1-null). We hypothesise that patients with a non-enzyme producing polymorphism have a higher risk of developing toxic injury owing to oxaliplatin. METHODS: In the nontumour-bearing liver, the presence of SOS was studied histopathologically. The genotype was determined by a semi-nested PCR. RESULTS: Thirty-two of the 55 (58%) patients showed SOS lesions, consisting of 27% mild, 22% moderate and 9% severe lesions. The GSTM1-null genotype was present in 25 of the 55 (46%). Multivariate analysis showed that the GSTM1-null genotype significantly correlated with the presence of (moderate-severe) SOS (P=0.026). CONCLUSION: The GSTM1-null genotype is an independent risk factor for SOS. This finding allows us, in association with other risk factors, to conceive a potential risk profile predicting whether the patient is at risk of developing SOS, before starting oxaliplatin, and subsequently might result in adjustment of treatment.
Subject(s)
Antineoplastic Agents/adverse effects , Colorectal Neoplasms/drug therapy , Glutathione Transferase/genetics , Hepatic Veno-Occlusive Disease/etiology , Liver Neoplasms/drug therapy , Organoplatinum Compounds/adverse effects , Polymorphism, Genetic/genetics , Adult , Aged , Aged, 80 and over , Colorectal Neoplasms/genetics , Colorectal Neoplasms/pathology , Female , Follow-Up Studies , Genotype , Humans , Liver Neoplasms/genetics , Liver Neoplasms/secondary , Male , Middle Aged , Oxaliplatin , Polymerase Chain Reaction , Prognosis , Risk FactorsABSTRACT
A bio-inspired durable anti-biofilm coating was developed for industrial stainless steel (SS) surfaces. Two polymers inspired from the adhesive and cross-linking properties of mussels were designed and assembled from aqueous solutions onto SS surfaces to afford durable coatings. Trypsin, a commercially available broad spectrum serine protease, was grafted as the final active layer of the coating. Its proteolytic activity after long immersion periods was demonstrated against several substrata, viz. a synthetic molecule, N-α-benzoyl-DL-arginine-p-nitroanilide hydrochloride (BAPNA), a protein, FTC-casein, and Gram-positive biofilm forming bacterium Staphylococcus epidermidis.
Subject(s)
Anti-Bacterial Agents/chemistry , Biofilms , Biofouling/prevention & control , Green Chemistry Technology , Stainless Steel/chemistry , Staphylococcus epidermidis/drug effects , Anti-Bacterial Agents/pharmacology , Bacterial Adhesion/drug effects , Bacterial Load , Benzoylarginine Nitroanilide/chemistry , Biofilms/drug effects , Caseins/chemistry , Cross-Linking Reagents/chemistry , Dihydroxyphenylalanine/chemistry , Enzyme Activation , Fluoresceins/chemistry , Indoles/chemistry , Microbial Viability , Microscopy, Fluorescence , Polymers/chemistry , Proteolysis , Static Electricity , Surface Properties , Trypsin/chemistryABSTRACT
The goal of this paper was to establish the durability profile of antibacterial multilayer thin films under storage and usage conditions. Thin films were built on stainless steel (SS) by means of a layer-by-layer process alternating a negatively charged polyelectrolyte, polyacrylic acid, with a cationic antibacterial peptide, nisin. SS coupons coated with the antibacterial film were challenged under environmental and usage conditions likely to be encountered in real-world applications. The change in antibacterial activity elicited by the challenge was used as an indicator of multilayer film resistance. Antibacterial SS samples could be stored for several weeks at 4°C in ambient air and antibacterial films were resistant to dipping and mild wiping in water and neutral detergent. The multilayer coating showed some weaknesses, however, that need to be addressed.
Subject(s)
Anti-Bacterial Agents/chemistry , Biofouling/prevention & control , Stainless Steel/chemistry , Surface PropertiesABSTRACT
Microorganisms are able to attach to, grow on, and ultimately form biofilms on a large variety of surfaces, such as industrial equipment, food contact surfaces, medical implants, prostheses and operating rooms. Once organized into biofilms, bacteria are difficult to remove and kill, which increases the risk of cross-contamination and infection. One way to address the problem may thus be to develop antibacterial, anti-adhesion, 'easy cleaning' surfaces. In this study, stainless steel (SS) surfaces with antibacterial properties were created by embedding several antimicrobial peptides in a multilayer film architecture. The biocidal effect of these surfaces was demonstrated against both Gram-positive and Gram-negative bacteria according to two ISO tests. Also, coating SS surfaces with either mucin or heparin led to a reduction of S. epidermidis adhesion of almost 95% vs the bare substratum. Finally, by combining both antibacterial and anti-adhesion biomolecules in the same multilayer film, SS surfaces with better cleanability were produced. This surface coating property may help to delay the buildup of a dead bacterial layer which is known to progressively reduce exposure of the coating, leading to an undesirable decrease in the antibacterial effect of the surface.