Prospects and Applications of Natural Blood-Derived Products in Regenerative Medicine

Currently, there are a number of therapeutic schemes used for the treatment of various types of musculoskeletal disorders. However, despite the use of new treatment options, therapeutic failure remains common due to impaired and delayed healing, or implant rejection. Faced with this challenge, in recent years regenerative medicine started looking for alternative solutions that could additionally support tissue regeneration. This review aims to outline the functions and possible clinical applications of, and future hopes associated with, using autologous or heterologous products such as antimicrobial peptides (AMPs), microvesicles (MVs), and neutrophil degranulation products (DGP) obtained from circulating neutrophils. Moreover, different interactions between neutrophils and platelets are described. Certain products released from neutrophils are critical for interactions between different immune cells to ensure adequate tissue repair. By acting directly and indirectly on host cells, these neutrophil-derived products can modulate the body’s inflammatory responses in various ways. The development of new formulations based on these products and their clinically proven success would give hope for significant progress in regenerative therapy in human and veterinary medicine.

Hemodynamic Monitoring in Sepsis—A Conceptual Framework of Macro- and Microcirculatory Alterations

Circulatory failure in sepsis is common and places a considerable burden on healthcare systems. It is associated with an increased likelihood of mortality, and timely recognition is a prerequisite to ensure optimum results. While there is consensus that aggressive source control, adequate antimicrobial therapy and hemodynamic management constitute crucial determinants of outcome, discussion remains about the best way to achieve each of these core principles. Sound cardiovascular support rests on tailored fluid resuscitation and vasopressor therapy. To this end, an overarching framework to improve cardiovascular dynamics has been a recurring theme in modern critical care. The object of this review is to examine the nature of one such framework that acknowledges the growing importance of adaptive hemodynamic support combining macro- and microhemodynamic variables to produce adequate tissue perfusion.

Biosafety of Nanoparticles Used in Orthodontics - A Literature Review

Nanotechnology is the science of manipulating matter, measured in the billionths of a nanometer, roughly the size of two or three atoms. It is widely used in our day-today life including its use in medicine and is considered as a vital current technology of the 21st century based on its economic and scientific potential. Its application is being experimented in various domains in orthodontics, from surface coatings to the development of novel materials. Orthodontic materials must have specific characteristics such as biological safety, functionality, and adequate tissue response. They have to pass specific biocompatibility tests to meet regulatory standards. Any material used in oral cavity might encourage unnecessary disturbance due to its complex and varied environment. The nanomaterials have many advantages in the field of orthodontics, especially with improved mechanical and antimicrobial properties. Nanoparticles can easily penetrate tissues and can affect biological behaviours at different levels. The introduction of nanotechnology gives better opportunities to both patient and orthodontist to new physicochemical, mechanical, and antibacterial properties of nanosized materials and can be used in coating orthodontic wires, elastomeric ligatures, and brackets, producing shape memory polymers and orthodontic bonding materials. The present review article focuses on the application of nanoparticles in orthodontics. This article presents a brief overview of nanotechnology, types of nanoparticles, biological safety of different nanoparticles used in orthodontics and their applications in the field of dentistry and orthodontics. KEY WORDS Nanoparticles, Biocompatibility, Orthodontics, Nanoscience

NGS Analysis Confirms Common TP53 and RB1 Mutations, and Suggests MYC Amplification in Ocular Adnexal Sebaceous Carcinomas

Ocular adnexal (OA) sebaceous carcinomas generally demonstrate more aggressive clinical and histopathological phenotypes than extraocular cases, but the molecular drivers implicated in their oncogenesis remain poorly defined. A retrospective review of surgical and ocular pathology archives identified eleven primary resection specimens of OA sebaceous carcinomas with adequate tissue for molecular analysis; two extraocular cases were also examined. Next-generation sequencing was used to evaluate mutations and copy number changes in a large panel of cancer-associated genes. Fluorescence in situ hybridization (FISH) confirmed MYC copy number gain in select cases, and immunohistochemistry to evaluate MYC protein expression. The commonest mutations occurred in TP53 (10/13) and RB1 (7/13). Additional mutations in clinically actionable genes, or mutations with a frequency of at least 25%, included the NF1 (3/12), PMS2 (4/12), ROS1 (3/12), KMT2C (4/12), MNX1 (6/12), NOTCH1 (4/12), PCLO (3/12), and PTPRT (3/12) loci. Low level copy number gain suggestive of amplification of the MYC locus was seen in two cases, and confirmed using FISH. MYC protein expression, as assessed by immunohistochemistry, was present in almost all sebaceous carcinoma cases. Our findings support the concept that alterations in TP53 and RB1 are the commonest alterations in sebaceous carcinoma, and suggest that MYC may contribute to the oncogenesis of these tumors.

Low Flow Venoarterial ECMO Support Management in Postcardiac Surgery Patient

Venoarterial extracorporeal membrane oxygenation (VA ECMO) aims to fully support heart and lung function in postcardiac patients, ensuring end-organ perfusion and allowing time for possible heart recovery. VA ECMO is considered the modified and extended form of cardiopulmonary bypass (CPB), which is used to provide adequate tissue oxygenation. ECMO and the associated management protocols will mechanically support the patient and allow for the optimization of all aspects of care for the period of time necessary for the recovery of native cardiac or respiratory function. Significant technical advancements have been made in the equipment and the clinical management available for short- and long-term ECMO application. There are various parameters that have to be considered to evaluate whether the level of perfusion in patients on VA ECMO is adequate, and the outcomes of patients depend on them.

Jehovah’s Witness survives severe favism complications: Advance provisions of treatment and new challenges for the physicians

The management of an acute hemolytic event in a patient suffering from favism is based on transfusion support to ensure adequate tissue oxygenation. If this measure could not be pursued, in case of severe anemia the risk of death from multiorgan failure would be relevant. Most of Jehovah’s Witness decline transfusion of whole blood and its main components, even in life-threatening situations. In this context, the treatment of severe anemia in these patients still represents a challenge from both medical and legal stand points. Authors report a case of a Jehovah’s Witness suffering from favism who refused blood transfusion, surviving a severe event of critical anemia associated with acute renal failure, thanks to the application of alternative therapies. It is essential that clinicians know the medico-legal aspects in such situations and are able to act promptly to support the patient’s vital functions, by complying with his/her wishes.

Adequate tissue sampling for the assessment of pathological tumor regression in pancreatic cancer

Standardized pathological evaluation of the regression assessment of neoadjuvant pancreatic cancer is necessary to improve prognostication and compare treatment outcomes in clinical trials. However, appropriate tissue sampling from surgically resected pancreatic cancer after neoadjuvant therapy has not been elucidated. We compared the tumor regression scores in the largest cancer slide determined macroscopically or histologically. We reviewed all slides and macroscopic photos of cut surfaces from resected pancreas of patients treated with neoadjuvant chemotherapy (n = 137; chemoradiotherapy or chemotherapy). The tumor regression scores (the Evans, College of American Pathologists, Japanese Pancreas Society grading systems, and Area of Residual Tumor [ART] score) were evaluated for the largest tumor slide determined by macroscopy or histologically as well as all slides from the resected pancreas. The largest cancer slides determined macroscopically and histologically were discrepant in 26% of the cases. Cancer cells were not detected in the largest macroscopically defined cut slides in 3%. Only ART scores assessed in the largest histological slides displayed significant difference in overall survival. We recommend obtaining the largest histological slides to provide adequate assessment for regression of neoadjuvant-treated pancreatic cancer. Sufficient sampling to detect the largest histological slides would be mandatory.

Collection and Handling of Thoracic Small Biopsy and Cytology Specimens for Ancillary Studies: Guidelines from the College of American Pathologists (CAP)

With a growing number of clinically relevant biomarkers needed to guide the management of patients with non-small cell lung cancer (NSCLC), pathologists are keenly aware of the need to collect adequate tissue not only for a diagnosis, but also for ancillary studies to provide predictive and prognostic information. Small specimens collected by minimally invasive techniques such as fine needle aspiration and core needle biopsy often fall short in meeting adequacy requirements for lung cancer molecular biomarkers. The College of American Pathologists (CAP) recently published an evidence-based clinical practice guideline, “Collection and Handling of Thoracic Small Biopsy and Cytology Specimens for Ancillary Studies”, to help direct clinicians and pathology laboratory personnel to optimally collect and handle thoracic small specimens for ancillary testing. This review summarizes the published guideline statements and provides a brief overview of the recommendations and how they impact the practice of pathology.