Tissue engineering and regenerative medicine approaches in colorectal surgery.

Tissue engineering and regenerative medicine (TERM) is an emerging field that has provided new therapeutic opportunities by delivering innovative solutions. The development of nontraditional therapies for previously unsolvable diseases and conditions has brought hope and excitement to countless individuals globally. Many regenerative medicine therapies have been developed and delivered to patients clinically. The technology platforms developed in regenerative medicine have been expanded to various medical areas; however, their applications in colorectal surgery remain limited. Applying TERM technologies to engineer biological tissue and organ substitutes may address the current therapeutic challenges and overcome some complications in colorectal surgery, such as inflammatory bowel diseases, short bowel syndrome, and diseases of motility and neuromuscular function. This review provides a comprehensive overview of TERM applications in colorectal surgery, highlighting the current state of the art, including preclinical and clinical studies, current challenges, and future perspectives. This article synthesizes the latest findings, providing a valuable resource for clinicians and researchers aiming to integrate TERM into colorectal surgical practice.

The role of collagen and crystallinity in the physicochemical properties of naturally derived bone grafts.

Xenografts are commonly used for bone regeneration in dental and orthopaedic domains to repair bone voids and other defects. The first-generation xenografts were made through sintering, which deproteinizes them and alters their crystallinity, while later xenografts are produced using cold-temperature chemical treatments to maintain the structural collagen phase. However, the impact of collagen and the crystalline phase on physicochemical properties have not been elucidated. We hypothesized that understanding these factors could explain why the latter provides improved bone regeneration clinically. In this study, we compared two types of xenografts, one prepared through a low-temperature chemical process (Treated) and another subsequently sintered at 1100°C (Sintered) using advanced microscopy, spectroscopy, X-ray analysis and compressive testing. Our investigation showed that the Treated bone graft was free of residual blood, lipids or cell debris, mitigating the risk of pathogen transmission. Meanwhile, the sintering process removed collagen and the carbonate phase of the Sintered graft, leaving only calcium phosphate and increased mineral crystallinity. Microcomputed tomography revealed that the Treated graft exhibited an increased high porosity (81%) and pore size compared to untreated bone, whereas the Sintered graft exhibited shrinkage, which reduced the porosity (72%), pore size and strut size. Additionally, scanning electron microscopy displayed crack formation around the pores of the Sintered graft. The Treated graft displayed median mechanical properties comparable to native cancellous bone and clinically available solutions, with an apparent modulus of 166 MPa, yield stress of 5.5 MPa and yield strain of 4.9%. In contrast, the Sintered graft exhibited a lower median apparent modulus of 57 MPa. It failed in a brittle manner at a median stress of 1.7 MPa and strain level of 2.9%, demonstrating the structural importance of the collagen phase. This indicates why bone grafts prepared through cold-temperature processes are clinically favourable.

Mesenchymal stem cells: A promising therapeutic avenue for non-alcoholic fatty liver disease.

Non-alcoholic fatty liver disease (NAFLD) is a pressing global health concern that is associated with metabolic syndrome and obesity. On the basis of the insights provided by Jiang et al, this editorial presents an exploration of the potential of mesenchymal stem cells (MSCs) for NAFLD treatment. MSCs have numerous desirable characteristics, including immunomodulation, anti-inflammatory properties, and tissue regeneration promotion, rendering them attractive candidates for NAFLD treatment. Recent preclinical and early clinical studies have highlighted the efficacy of MSCs in improving liver function and reducing disease severity in NAFLD models. However, MSC heterogeneity, long-term safety concerns, and unoptimized therapeutic protocols remain substantial challenges. Addressing these challenges through standardized protocols and rigorous clinical trials is essential to the safe and successful application of MSCs in NAFLD management. Continued research into MSC mechanisms and therapeutic optimization is required to improve treatments for NAFLD and related liver diseases.

Cell-based therapy in the treatment of musculoskeletal diseases.

A limited number of tissues can spontaneously regenerate following injury, and even fewer can regenerate to a state comparable to mature, healthy adult tissue. Mesenchymal stem cells (MSCs) were first described in the 1960s-1970s by Friedenstein et al as a small population of bone marrow cells with osteogenic potential and abilities to differentiate into chondrocytes. In 1991, Arnold Caplan coined the term "mesenchymal cells" after identifying these cells as a theoretical precursor to bone, cartilage, tendon, ligament, marrow stroma, adipocyte, dermis, muscle, and connective tissues. MSCs are derived from periosteum, fat, and muscle. Another attractive property of MSCs is their immunoregulatory and regenerative properties, which result from crosstalk with their microenvironment and components of the innate immune system. Collectively, these properties make MSCs potentially attractive for various therapeutic purposes. MSCs offer potential in sports medicine, aiding in muscle recovery, meniscal tears, and tendon and ligament injuries. In joint disease, MSCs have the potential for chondrogenesis and reversing the effects of osteoarthritis. MSCs have also demonstrated potential application to the treatment of degenerative disc disease of the cervical, thoracic, and lumbar spine.

An evaluation of the effectiveness of platelet rich plasma epidural injections for low back pain suspected to be of disc origin - A pilot study with one-year follow-up.

Summary of background data: Low back pain of disc origin is common yet challenging to treat. Intradiscal platelet rich plasma (PRP) has been advocated, but is associated with risk of discitis. Epidural PRP is less invasive and avoids this risk. Few studies exist evaluating effectiveness and safety of epidural PRP for discogenic low back pain without radiculopathy and the follow-up of the studies tends to be short. Objective: Prospectively evaluate for 12 months the effectiveness of PRP epidural injections for patients with low back pain without radiculopathy, suspected to be of disc origin. Methods: 11 consecutive patients with refractory low back pain suspected to be of disc origin (compatible clinical assessment; negative lumbosacral medial branch blocks (MBBs) and/or magnetic resonance imaging (MRI) with high intensity zone (HIZ), Modic 1 or 2 changes) participated. Each underwent one (n = 5) or two (n = 6) epidural injections (caudal or interlaminar). The PRP was leukocyte/red cell depleted with an average platelet concentration of ∼2X whole blood. Numerical rating scale (NRS), Pain Disability Quality-Of-Life Questionnaire (PDQQ) score, Oswestry Disability Index (ODI) score, effect on analgesic intake, treatment satisfaction and endorsement were recorded prior to and at 3, 6 and 12-months post-treatment. Results: Significant improvements in pain and disability were documented post-treatment. Pre-, 3, 6, and 12-month post mean(sd) NRS scores were 7.8(1.8), 5.8(2.7), 5.1(2.5), 4.9(2.8) respectively (F = 7.2; p = 0.002). At 12 months post PRP epidural, the mean improvement in NRS was 36%, 36% had experienced ≥50% pain relief (95% confidence interval (CI): 2%, 70%), and 73% achieved minimal clinically important differences (MCID) (95% CI: 41%, 100%). Similar magnitude improvements in disability (PDQQ and ODI) were documented. At 1-year post, 50% of analgesic users had reduced intake, 91% were satisfied with the treatment and would recommend the procedure to family and friends. No complications were reported. Discussions/conclusion: This pilot project suggests that PRP epidural injections provide modest yet significant improvements in pain and disability that lasts at least 12 months in patients with low back pain suspected to be of disc origin. Additional research including larger sample size and robust study design is encouraged.

Exploring New Horizons: Advancements in Cartilage Tissue Engineering Under Space Microgravity.

Novel investigations of how microgravity affects cellular and tissue development have recently been made possible by the multidisciplinary fusion of tissue engineering and space science. This review examines the intersection of cartilage tissue engineering (CTE) and space science, focusing on how microgravity affects cartilage development. Space microgravity induces distinct physiological changes in chondrocytes, including a 20-30% increase in cell diameter, a 1.5- to 2-fold increase in proliferation rates, and up to 3-fold increases in chondrogenic markers such as SOX9 and collagen type II. These cellular alterations impact extracellular matrix composition and tissue structure. Space-optimized bioreactors using dynamic culture methods replicate physiological conditions and enhance tissue growth, but the absence of gravity raises concerns about the mechanical properties of engineered cartilage. Key research areas include the role of growth factors in cartilage development under microgravity, biocompatibility and degradation of scaffold materials in space, and in situ experiments on space stations. This review highlights the opportunities and challenges in leveraging microgravity for CTE advancements, emphasizing the need for continued research to harness space environments for therapeutic applications in cartilage regeneration. The multidisciplinary fusion of tissue engineering and space science opens novel avenues for understanding and improving cartilage tissue engineering, with significant implications for the future of biomedical applications in space and on Earth.

Role of Autologous Platelet-Rich Fibrin in Chronic Non-healing Ulcers With Various Etiologies in a Tertiary Care Rehabilitation Centre: A Case Series.

Introduction Chronic non-healing ulcers are defined as a discontinuity or break in the integrity of skin that is not healing in a reasonable period of time due to an underlying systemic etiology. Despite using conventional initial treatment and many other available dressing options, such wounds are difficult to completely heal, thus affecting the progress of rehabilitation measures and compromising functional improvement and quality of life. Materials and methods In this case series, platelet-rich fibrin (PRF) was applied to eight wounds from six patients. The patients included had various etiologies (including spinal cord injury, peripheral vascular disease, Guillain-Barré syndrome, and diabetic foot ulcer) with chronic non-healing wounds over different anatomical locations on the body. Pressure ulcer scale for healing (PUSH) score, surface area, and volume of the wounds were evaluated and monitored weekly after PRF dressing. We have applied PRF every week. On average, two PRF dressings were applied, the maximum being three applications. Results The maximum healing rate in terms of PUSH score was observed to be 3.84% per day, and the minimum was 1.19% per day. The maximum healing rate in terms of surface area was observed to be 5.89% per day, and the minimum was 1.78% per day. Three of the wounds showed complete closure. The maximum follow-up period was 10 weeks. The percentage mean Functional Independence Measure (FIM) improvement was calculated to be 15.87% ± 14.04 during the course of hospitalization after PRF application. Conclusion Based on the results, we can conclude that PRF showed accelerated improvement in the healing of chronic non-healing ulcers of various etiologies at different anatomical locations. It has proven to be a safe and effective method, thereby improving their quality of life and functional independence in performing activities of daily living. To our knowledge till date, no other study in a rehabilitation setting has been done on patients having non-healing ulcers due to various etiologies and at different anatomical locations.

A comprehensive review of energy harvesting technologies for sustainable electric vehicles.

This review paper provides a comprehensive examination of energy harvesting technologies tailored for electric vehicles (EVs). Against the backdrop of the automotive industry's rapid evolution towards electrification and sustainability, the paper explores a diverse range of techniques. The analysis encompasses the strengths, weaknesses, applicability in various scenarios, and potential implications for the future of EVs. A key finding of the review highlights regenerative braking as a pivotal and highly efficient method for energy recovery, particularly in urban settings. In addition to extending battery life, regenerative braking significantly boosts energy efficiency of EVs. The paper also delves into the challenges associated with integrated solar energy systems, emphasizing issues related to efficiency and weather dependency. Kinetic energy recovery systems (KERS) are discussed for their substantial power boost during acceleration in both motorsports and road cars. Additionally, the review explores regenerative shock absorbers, which capture energy from suspension movement, enhancing ride comfort and increasing vehicle energy economy, especially on uneven terrain. The piezoelectric system, though intriguing, is found to have low power output from mechanical vibration, prompting further exploration for integration into EVs. However, complexities and cost considerations arise in their integration with the vehicle's suspension system.

A cellular disease model toward gene therapy of TGM1-dependent lamellar ichthyosis.

Lamellar ichthyosis (LI) is a chronic disease, mostly caused by mutations in the TGM1 gene, marked by impaired skin barrier formation. No definitive therapies are available, and current treatments aim at symptomatic relief. LI mouse models often fail to faithfully replicate the clinical and histopathological features of human skin conditions. To develop advanced therapeutic approaches, such as combined ex vivo cell and gene therapy, we established a human cellular model of LI by efficient CRISPR-Cas9-mediated gene ablation of the TGM1 gene in human primary clonogenic keratinocytes. Gene-edited cells showed complete absence of transglutaminase 1 (TG1) expression and recapitulated a hyperkeratotic phenotype with most of the molecular hallmarks of LI in vitro. Using a self-inactivating γ-retroviral (SINγ-RV) vector expressing transgenic TGM1 under the control of its own promoter, we tested an ex vivo gene therapy approach and validate the model of LI as a platform for pre-clinical evaluation studies. Gene-corrected TGM1-null keratinocytes displayed proper TG1 expression, enzymatic activity, and cornified envelope formation and, hence, restored proper epidermal architecture. Single-cell multiomics analysis demonstrated proviral integrations in holoclone-forming epidermal stem cells, which are crucial for epidermal regeneration. This study serves as a proof of concept for assessing the potential of this therapeutic approach in treating TGM1-dependent LI.

Advancements in cell-based therapies for thermal burn wounds: a comprehensive systematic review of clinical trials outcomes.

BACKGROUND: Burn trauma is one of the major causes of morbidity and mortality worldwide. The standard management of burn wounds consists of early debridement, dressing changes, surgical management, and split-thickness skin autografts (STSGs). However, there are limitations for the standard management that inclines us to find alternative treatment approaches, such as innovative cell-based therapies. We aimed to systematically review the different aspects of cell-based treatment approaches for burn wounds in clinical trials. METHODS: A systematic search through PubMed, Medline, Embase, and Cochrane Library databases was carried out using a combination of keywords, including "Cell transplantation", "Fibroblast", "Keratinocyte", "Melanocyte", or "Stem Cell" with "Burn", "Burn wound", or "Burn injury". Firstly, titles and abstracts of the studies existing in these databases until "February 2024" were screened. Then, the selected studies were read thoroughly, and considering the inclusion and exclusion criteria, final articles were included in this systematic review. Moreover, a manual search was performed through the reference lists of the included studies to minimize the risk of missing reports. RESULTS: Overall, 30 clinical trials with 970 patients were included in our study. Considering the type of cells, six studies used keratinocytes, nine used fibroblasts, eight used combined keratinocytes and fibroblasts, one study used combined keratinocytes and melanocytes, five used combined keratinocytes and fibroblasts and melanocytes, and one study used mesenchymal stem cells (MSCs). Evaluation of the preparation type in these studies showed that cultured method was used in 25 trials, and non-cultured method in 5 trials. Also, the graft type of 17 trials was allogeneic, and of 13 other trials was autologous. CONCLUSIONS: Our study showed that employing cell-based therapies for the treatment of burn wounds have significant results in clinical studies and are promising approaches that can be considered as alternative treatments in many cases. However, choosing appropriate cell-based treatment for each burn wound is essential and depends on the situation of each patient.

A two-step strategy to expand primary human hepatocytes in vitro with efficient metabolic and regenerative capacities.

BACKGROUND: Primary human hepatocytes (PHHs) are highly valuable for drug-metabolism evaluation, liver disease modeling and hepatocyte transplantation. However, their availability is significantly restricted due to limited donor sources, alongside their constrained proliferation capabilities and reduced functionality when cultured in vitro. To address this challenge, we aimed to develop a novel method to efficiently expand PHHs in vitro without a loss of function. METHODS: By mimicking the in vivo liver regeneration route, we developed a two-step strategy involving the de-differentiation/expansion and subsequent maturation of PHHs to generate abundant functional hepatocytes in vitro. Initially, we applied SiPer, a prediction algorithm, to identify candidate small molecules capable of activating liver regenerative transcription factors, thereby formulating a novel hepatic expansion medium to de-differentiate PHHs into proliferative human hepatic progenitor-like cells (ProHPLCs). These ProHPLCs were then re-differentiated into functionally mature hepatocytes using a new hepatocyte maturation condition. Additionally, we investigated the underlying mechanism of PHHs expansion under our new conditions. RESULTS: The novel hepatic expansion medium containing hydrocortisone facilitated the de-differentiation of PHHs into ProHPLCs, which exhibited key hepatic progenitor characteristics and demonstrated a marked increase in proliferation capacity compared to cells cultivated in previously established expansion conditions. Remarkably, these subsequent matured hepatocytes rivaled PHHs in terms of transcriptome profiles, drug metabolizing activities and in vivo engraftment capabilities. Importantly, our findings suggest that the enhanced expansion of PHHs by hydrocortisone may be mediated through the PPARα signaling pathway and regenerative transcription factors. CONCLUSIONS: This study presents a two-step strategy that initially induces PHHs into a proliferative state (ProHPLCs) to ensure sufficient cell quantity, followed by the maturation of ProHPLCs into fully functional hepatocytes to guarantee optimal cell quality. This approach offers a promising means of producing large numbers of seeding cells for hepatocyte-based applications.

Regenerative medicine in Obstetrics & Gynecology: Current status under the Act on the Safety of Regenerative Medicine in Japan.

Introduction: While the provision of unapproved regenerative medicine has been problematic worldwide, few studies have examined the implementation status of regenerative medicine (RM) in the specific field. This study aimed to determine the current status of therapy and clinical research in the obstetrics and gynecology (OBGYN) in Japan under the Act on the Safety of Regenerative Medicine (RM Act). Methods: Detailed data were extracted from publicly available websites provided by the Ministry of Health, Labour, and Welfare. We extracted descriptive details, including risk classification of the RM Act, modality, target disease, locality, institution, and administration route. For therapy, the price for each modality was evaluated. Results: The total number of therapeutic provision plans in OBGYN (1.9% of RM in Japan) are classified as Class II (moderate) risk. Most were administered in clinics in urban areas for treating endometrial or ovarian infertility by locally administering platelet-rich plasma (PRP) or autologous mesenchymal stem cells (MSCs). The price using MSCs is approximately eight times more expensive that of those involving PRP (1832.1 ± 1139.8 vs 240.8 ± 106.5 thousand yen, p < 0.0001). Regarding research, four plans (2.2%) were submitted to target implantation failure and advanced gynecological cancer using autologous lymphocytes, dendritic cells, or MSCs. Conclusion: The RM Act permits knowledge of the current status of regenerative medicine even for unapproved uses in a specific clinical field. The study findings shall prompt a worldwide discussion regarding the required regulations for therapy and clinical research of RM.

Clinical report of the immediate placement implants in patients aged 80 and over: Five cases and a short review.

With the population aging, the proportion of elderly individuals is expected to increase, and the proportion of individuals over 80 is also likely to increase. Given that the population is aging and life expectancy is increasing, elderly patients who have lost thei teeth will also increase. Impaired masticatory function caused by tooth loss is a risk factor for cognitive decline and frailty, and neglecting to treat tooth loss is a critical issue. In this report, five patients over 80 requested dental implants for new missing teeth and underwent immediate implant placement. All patients were treated by the same surgeon using the same technique, materials, and dental implants. Five elements were measured for the peri-implant bone from the cone-beam computed tomography images. All patients were followed for three or more years and exhibited good progress without any abnormal findings in their oral cavities or notable radiographic abnormalities such as bone absorption or peri-implantitis. Compared to conventional treatment with delayed placement, combining immediate implant placement and regenerative medicine for fixed superstructures may be the better option for missing tooth replacement if the conditions are suitable. Thus, this treatment modality may improve the quality of life in elderly patients, especially super elderly patients.

Local delivery of platelet-derived factors mitigates ischemia and preserves ovarian function through angiogenic modulation: A personalized regenerative strategy for fertility preservation.

As the most prominent and ideal modality in female fertility preservation, ovarian tissue cryopreservation, and transplantation often confront the challenge of ischemic damage and follicular loss from avascular transplantation. To surmount this impediment, we engineered a novel platelet-derived factors-encapsulated fibrin hydrogel (PFH), a paradigmatic biomaterial. PFH encapsulates autologous platelet-derived factors, utilizing the physiological blood coagulation cascade for precise local delivery of bioactive molecules. In our study, PFH markedly bolstered the success of avascular ovarian tissue transplantation. Notably, the quantity and quality of follicles were preserved with improved neovascularization, accompanied by decreased DNA damage, increased ovulation, and superior embryonic development rates under a Low-concentration Platelet-rich plasma-derived factors encapsulated fibrin hydrogel (L-PFH) regimen. At a stabilized point of tissue engraftment, gene expression analysis mirrored normal ovarian tissue profiles, underscoring the effectiveness of L-PFH in mitigating the initial ischemic insult. This autologous blood-derived biomaterial, inspired by nature, capitalizes on the blood coagulation cascade, and combines biodegradability, biocompatibility, safety, and cost-effectiveness. The adjustable properties of this biomaterial, even in injectable form, extend its potential applications into the broader realm of personalized regenerative medicine. PFH emerges as a promising strategy to counter ischemic damage in tissue transplantation, signifying a broader therapeutic prospect. (197 words).

Performance of red blood cell indices for the detection of reticulocytosis in anemic and non-anemic dogs in Taiwan.

Reticulocyte counts (RETIC) are considered the gold standard in detecting an erythroid bone marrow response (BMR) in anemic and non-anemic dogs. Reticulocytosis without anemia (RWA) is a potential indicator of disease. The prevalence of anemia or RWA, as well as the effectiveness of red blood cell (RBC) indices in identifying a BMR, may vary based on geographical locations and breed differences. The purpose of the study was to determine the prevalence of regenerative and nonregenerative anemia, and RWA in pet dogs of Taiwan, and to assess the sensitivity and specificity of combined increased mean cell volume and decreased mean cell hemoglobin concentration (iMCV+dMCHC) to detect reticulocytosis in this population. The final population analysis consisted of 149,076 dogs. A cross sectional, retrospective analysis of complete blood count (CBC) samples from a field of automated hematology analyzers in Taiwan from December 1, 2018 through December 31, 2020 was performed. Among 149,076 dogs, 11.8% (n=17,600) had reticulocytosis (RETIC > 110K/µl) and 21.8% (n=32,474) had anemia (HCT < 37.3%). Of 32,474 anemic dogs, 17.8% (n=5,789) had reticulocytosis. Of 116,602 dogs without anemia, 10.1% (n=11,776) had reticulocytosis. Across all dogs, sensitivity/specificity of iMCV+dMCHC to detect BMR was 4.3% and 99.4%, respectively compared to RETIC. Among anemic dogs, sensitivity/specificity of iMCV+dMCHC to detect BMR was 9.8% and 99.2%, respectively. Among non-anemic dogs, sensitivity/specificity of iMCV+dMCHC to detect BMR was 1.6% and 99.5%, respectively. Therefore, most regenerative anemias and cases of RWA did not have a combined iMCV+dMCHC. To avoid overlooking potential illness, RETIC should be evaluated regardless of whether patients have anemia or not.

Patient, parent and professional expert perspectives on personalized regenerative implants: a qualitative focus group study.

Background: Perspectives of patients, parents and professional experts on personalized regenerative implants for regenerative medicine purposes are largely unknown.Method: To better understand these perspectives, we conducted four focus groups with professional experts of mixed European nationality (n = 8), Dutch patients with regular implants (n = 8), Dutch and Belgian (n = 5) and Spanish (n = 8) parents of children with cleft palate.Results: Two overarching themes were identified: 'patient-centered research and care' and 'ambivalent attitudes toward personalized regenerative implants'.Discussion: The results reveal that stakeholders should adopt a participatory rather than an impairment discourse and address the ambivalence among professional experts, patients and parents.Conclusion: Considering stakeholder perspectives facilitates ethical and responsible development and use of personalized regenerative implants.

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Industry updates from the field of stem cell research and regenerative medicine in March 2024.

Latest developments in the field of stem cell research and regenerative medicine compiled from publicly available information and press releases from non-academic institutions in March 2024.

Regenerative medicine industry news digest, March 2024.

Transcriptomic Analysis Reveals the Heterogeneous Role of Conducting Films Upon Electrical Stimulation.

Central nervous system (CNS) injuries and neurodegenerative diseases have markedly poor prognoses and can result in permanent dysfunction due to the general inability of CNS neurons to regenerate. Differentiation of transplanted stem cells has emerged as a therapeutic avenue to regenerate tissue architecture in damaged areas. Electrical stimulation is a promising approach for directing the differentiation outcomes and pattern of outgrowth of transplanted stem cells, however traditional inorganic bio-electrodes can induce adverse effects such as inflammation. This study demonstrates the implementation of two organic thin films, a polymer/reduced graphene oxide nanocomposite (P(rGO)) and PEDOT:PSS, that have favorable properties for implementation as conductive materials for electrical stimulation, as well as an inorganic indium tin oxide (ITO) conductive film. Transcriptomic analysis reveals that electrical stimulation improves neuronal differentiation of SH-SY5Y cells on all three films, with the greatest effect for P(rGO). Unique material- and electrical stimuli-mediated effects are observed, associated with differentiation, cell-substrate adhesion, and translation. The work demonstrates that P(rGO) and PEDOT:PSS are highly promising organic materials for the development of biocompatible, conductive scaffolds that will enhance electrically-aided stem cell therapeutics for CNS injuries and neurodegenerative diseases.

First case of autochthonous Angiostrongylus vasorum infection in a Norwegian dog.

A fifteen-month-old Pembroke Welsh corgi with respiratory distress, exercise intolerance, and moderate regenerative anemia was referred to The Norwegian University of Life Sciences, Small Animal Hospital.Hematology revealed moderate regenerative anemia without evidence of hemolysis. Thoracic radiographs showed a generalized mixed interstitial to alveolar lung pattern and enlarged pulmonary arteries. Changes suggestive of moderate pulmonary hypertension were noted on echocardiography. Baermann fecal diagnostic flotation identified large numbers of Angiostrongylus vasorum larvae, and the AngioDetect serological antigen test was positive. The dog was treated with a two-week course with fenbendazole (51 mg/kg q24h po) and topical imidacloprid/moxidectin (250 mg/62.5 mg) and a one-week course with sildenafil (0.45 mg/kg q12h po). Complete clinical, clinicopathological and echocardiographic resolution was observed after only four weeks. Rapid improvement of echocardiographic abnormalities in cases with suspected pulmonary hypertension is not usually reported in cases with angiostrongylosis.Infection with A. vasorum should be considered in dogs with respiratory signs and bleeding tendencies, even in countries with no endemic history or reported cases.

Adverse events related to platelet-rich plasma therapy and future issues to be resolved.

Platelet-rich plasma (PRP) is the portion of plasma with a platelet concentration above baseline that is recovered through centrifugation of autologous blood. PRP therapy is currently used for wound healing and pain relief in diverse medical fields. Although there have been recent reports of adverse events (AEs) possibly related to PRP treatment, the safety profile of PRP treatment remains unclear. Therefore, this review discusses the risks inherent in PRP therapy and the current issues by surveying reports on AEs associated with PRP treatment within different fields. PubMed was searched for research articles referring to AEs associated with PRP therapy from inception to January 2024. Literature survey revealed that PRP therapy may involve several AEs, including postoperative infections, blindness, inflammation, allergic reactions, and nodule development. The most commonly reported AE was postoperative infections. Since PRP therapy generally proceeds in the process of blood collection, manufacturing, and administration to patients, it is conjectured that PRP may have been contaminated with microorganisms at some point in this series of processes, leading to bacterial infection. Additionally, because PRP cannot be sterilized like pharmaceuticals, it is important to prevent microbial contamination during each PRP treatment process. However, the specific process that involves the risk of microbial contamination remains unclear. To take measures to prevent microbial contamination of PRP, it may be necessary to elucidate the risk factors for microbial contamination during PRP treatment. It may be important to elucidate the effectiveness and risks of PRP therapy as well as to establish a follow-up system after PRP treatment. Currently, most reports of AEs related to PRP therapy are case reports; therefore, the accumulation of high-quality evidence and detailed verification are necessary to determine the causal relationship between PRP therapy and each AE.