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Tissue Engineering. Part B, Reviews Aug 2020Extensive dental and periodontal defects are frequent and with a limited regenerative potential. Tissue engineering could be a promising tool to obtain personalized oral...
Extensive dental and periodontal defects are frequent and with a limited regenerative potential. Tissue engineering could be a promising tool to obtain personalized oral grafts. However, current research shows a lack of engineered oral tissues. This is explained by the difficulty to engineer blood vessel systems, impairing the connection to the host tissue and the graft success. Various strategies were used to engineer vascularized tissues and reported successful results, thus needing a clear analysis of the current state of art in oral tissue engineering. This systematic review aimed at studying the critical factors and techniques used to engineer a prevascularized oral tissue graft. PubMed, Cochrane Library, and SCOPUS databases were searched over the last 5 years following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Out of 638 screened studies, 24 were included in the systematic review according to strict inclusion and exclusion criteria and focusing on higher connection to the host vasculature. Animal models were all rodents, and subcutaneous implantation was the most used intervention. Studies presented low-to-unclear risk of bias according to the Systematic Review Center for Laboratory Animal Experimentation tool. Endothelial cells were mainly human umbilical vein endothelial cells, while stromal cells were most of the time oral or mesenchymal stem cells. Coculture of both types of cells at a 1:1 ratio was the most common technique used to obtain vascular networks, and some studies precultured grafts up to 3 weeks to enable network formation before implantation. Prevascularized grafts were produced by various tissue engineering technologies, including cell seeding and/or embedding, cell sheets, and spheroids. All studies reported a statistically significant faster and higher connection to host of prevascularized constructs compared to controls. Vessel networks were indeed denser, with a higher portion of lumen containing erythrocytes and blood flow increased. By assessing the relevant studies on the subject, this systematic review showed that engineered prevascularization proved to be an interesting approach to improve graft connection to the host vasculature and respective specific cell and scaffold criteria. Further studies on enhanced scaffolds and larger animals seem necessary to confirm these promising results with more voluminous grafts and get closer to native human tissues and applications. Impact statement Autologous oral grafts display limitations in terms of revascularization and morbidity of donor sites, despite being the gold standard. This systematic review aimed at clarifying existing data regarding techniques to engineer prevascularized oral grafts. Tissue engineering techniques, using cocultures of endothelial and oral stromal cells, proved to be an efficient way to enhance and accelerate the connection of the graft to the host vasculature. Engineered prevascularization appears to be a promising way to improve the connection to the host and the vascularization of grafts, especially when voluminous. Large animal and human studies are necessary to allow clinical translation.
Topics: Animals; Humans; Mouth Diseases; Mouth Mucosa; Neovascularization, Physiologic; Tissue Engineering
PubMed: 32597330
DOI: 10.1089/ten.TEB.2020.0093 -
Transplantation Reviews (Orlando, Fla.) Apr 2022Isolated cases of extracorporeal membrane oxygenation (ECMO) in patients with hepatopulmonary syndrome (HPS) undergoing liver transplantation (LT) have been reported... (Review)
Review
BACKGROUND
Isolated cases of extracorporeal membrane oxygenation (ECMO) in patients with hepatopulmonary syndrome (HPS) undergoing liver transplantation (LT) have been reported with increasing frequency. We aimed to systemically review and synthesize the available literature on ECMO use in this population.
METHODS
A systematic literature review of the PubMed, Web of Science, Cochrane Library, and Embase databases (end-of-search date: November 14, 2021) was conducted in accordance with the PRISMA statement. Eligible studies presented clinical parameters and outcomes of adult or pediatric patients with HPS receiving ECMO support at the time of, or following, LT.
RESULTS
Sixteen studies from 4 continents reporting on 17 patients who were initiated on ECMO prior to (n = 2), during (n = 1) or after LT (n = 14) were included. Nine of the 16 studies were published between 2019 and 2021. The median pre-LT PaO was 38.0 mmHg (IQR 35.0-52.0). The median time from LT to ECMO initiation was 7 days (IQR, 3-12). Six patients (50%, n = 6 of 12) were extubated post-LT, before deterioration, development of refractory hypoxemia, and initiation of ECMO. Most patients were cannulated with a venovenous configuration (75%, n = 12 of 16). Most patients cannulated with a venoarterial or veno-arterial-venous strategy (75%, n = 3 of 4) had concurrent hemodynamic instability. The median total time on ECMO was 13 days (IQR 10-29). Using linear regression, for patients cannulated postoperatively, each day between LT and ECMO initiation was associated with a 3.5-day increase in total ECMO duration (95%CI: 2.23-4.73, p < 0.001, R = 73.7%). The median postoperative intensive care unit length of stay was 40 days (IQR, 37-61) and hospital length of stay was 59.5 days (IQR 42-77). 82.4% of patients (14 of 17) survived to discharge.
CONCLUSIONS
ECMO is feasible in patients with HPS undergoing LT and appears to be associated with better outcomes compared to other causes of cardiopulmonary failure in LT patients. As the volume of experience grows, ECMO may become a central part of perioperative support in LT patients with severe HPS.
Topics: Adult; Child; Extracorporeal Membrane Oxygenation; Hepatopulmonary Syndrome; Humans; Liver Transplantation
PubMed: 35413506
DOI: 10.1016/j.trre.2022.100693 -
Frontiers in Oncology 2022Tumors can survive environmental and metabolic stress by triggering homeostatic responses that re-establish the pre-stress status and permit them to grow and thrive. The...
Tumors can survive environmental and metabolic stress by triggering homeostatic responses that re-establish the pre-stress status and permit them to grow and thrive. The endoplasmic reticulum (ER) is the organelle where proteins undergo post-translational modifications and are folded and exported to the secretory pathway. Its environment and activity are therefore fundamental for proteostasis, i.e., the plethora of mechanisms controlling protein formation, folding, degradation, and secretion, needed to assure protein balance and cellular health. In different tumor-related conditions, such as after the activation of oncogenes or under hypoxia and nutrient deprivation, the ER experiences stress, triggered by a high load of proteins to be folded compared to the limited folding capacity of the organelle. As a consequence, three ER membrane sensors and the related unfolded protein response (UPR) are activated. The UPR comprises a complex interconnection between signal transduction pathways that promote a homeostatic response that acts by increasing the amount of protein chaperones and of proteins involved in ER-associated protein degradation (ERAD) on one hand and attenuating protein translation on the other. ER-phagy, literally "eating" the ER, is part of another homeostatic response consisting of the clearance of non-functional ER portions including misfolded proteins. This response is also activated by a set of dedicated ER-phagy receptors after ER stimuli, which overlap the stimuli generating ER stress. Thus, the UPR and ER-phagy are two closely related homeostatic mechanisms that cooperate in re-establishing ER homeostasis. However, while the role of the UPR in favoring cancer growth and thriving by promoting angiogenesis, metastasis, chemotherapy resistance, and epithelial-to-mesenchymal transition is consolidated, that of ER-phagy is still in its infancy. This essay provides an overview of emerging concepts on ER stress, the UPR, and ER-phagy and their crosstalk in tumorigenesis. We also critically review new findings on their pharmacological targeting in cancer.
PubMed: 36408145
DOI: 10.3389/fonc.2022.997235 -
ASAIO Journal (American Society For... Jan 2023Right ventricular injury (RVI) in the context of acute respiratory distress syndrome (ARDS) is well recognized as an important determinant risk factor of mortality.... (Meta-Analysis)
Meta-Analysis
Right Ventricular Injury Increases Mortality in Patients With Acute Respiratory Distress Syndrome on Veno-Venous Extracorporeal Membrane Oxygenation: A Systematic Review and Meta-Analysis.
Right ventricular injury (RVI) in the context of acute respiratory distress syndrome (ARDS) is well recognized as an important determinant risk factor of mortality. Veno-venous extracorporeal membrane oxygenation (VV-ECMO) is part of the algorithm for the management of patients with severe ARDS and severely impaired gas exchange. Although VV-ECMO may theoretically protect the RV it is uncertain to what degree RVI persists despite VV-ECMO support, and whether it continues to influence mortality after ECMO initiation. The aim of this systematic review and meta-analysis was to investigate the impact of RVI on mortality in this context, testing the hypothesis that RVI worsens mortality in this cohort. We performed a systematic search that identified seven studies commenting on RVI and mortality in patients with ARDS receiving VV-ECMO. The presence of RVI was associated with greater mortality overall (odds ratios [OR]: 2.72; 95% confidence intervals [CI]: 1.52-4.85; p < 0.00) and across three subgroups (RV dilatational measures: OR: 3.51; 95% CI: 1.51-8.14; p < 0.01, RV functional measures: OR: 1.84; 95% CI: 0.99-3.42; p = 0.05, RV measurements post-ECMO initiation: OR: 1.94; 95% CI: 1.01-3.72; p < 0.05). Prospective studies are needed to investigate the causal relationship between RVI and mortality in this patient group and the best management strategies to reduce mortality.
Topics: Humans; Extracorporeal Membrane Oxygenation; Respiratory Distress Syndrome; Risk Factors; Heart Ventricles; Retrospective Studies
PubMed: 36375040
DOI: 10.1097/MAT.0000000000001854 -
Annals of Medicine and Surgery (2012) Jul 2023Despite the significant research and development of COVID-19 diagnostic and therapeutic approaches, the virus still poses a concern, particularly to groups that are...
UNLABELLED
Despite the significant research and development of COVID-19 diagnostic and therapeutic approaches, the virus still poses a concern, particularly to groups that are already vulnerable. Several individuals experienced cardiac problems like myocardial infarction, arrhythmia, heart failure, cardiomyopathy, myocarditis, and pericarditis after they had recovered from the infection. Early diagnosis and timely management of sequelae are part of the therapy. However, there are gaps in the knowledge of the diagnostic and definitive treatment options for COVID-19 myocarditis. This review focuses on myocarditis associated with COVID-19.
OBJECTIVE
This systemic review provides the most recent overview of myocarditis caused by COVID-19, including clinical manifestations, diagnostic techniques, available treatments, and outcomes.
METHODS
The PubMed, Google Scholar, and ScienceDirect servers were used to conduct a systematic search in compliance with the PRISMA guidelines. Boolean search terms included "(COVID-19)" OR "(COVID19)" OR "(COVID-19 VIRUS INFECTION)" AND "(MYOCARDITIS)". The results were tabulated and analyzed.
RESULTS
A total of 32 studies, including 26 case reports and 6 case series, were included in the final analysis, and 38 cases of COVID-19-associated myocarditis were analyzed. Middle-aged men constituted the most affected population (60.52%). Dyspnoea (63.15%), chest pain or discomfort (44.73%), and fever (42.10%) were the prevalent presentations. ST-segment abnormalities were reported in 48.38% of cases on electrocardiography testing. Leucocytic infiltration (60%) was the frequent finding obtained on endomyocardial biopsy. Cardiac magnetic resonance imaging yielded myocardial oedema (63.63%), and late gadolinium enhancement (54.54%) as the most common findings. Reduced ejection fraction (75%) was the frequent result obtained on echocardiography. Corticosteroids (76.31%) and immunomodulators (42.10%) were the well-established in-hospital medications. Veno-arterial extracorporeal membrane oxygenation (35%) was the most common intervention used to support the treatment. The frequent in-hospital complications were cardiogenic shock (30.76%), followed by pneumonia (23.07%). The mortality rate was 7.9%.
CONCLUSION
Early detection and timely management of myocarditis are essential to reduce the risk of developing further complications. It is crucial to emphasize the need to evaluate COVID-19 as a possible cause of myocarditis in populations that are young and healthy to avoid fatal consequences.
PubMed: 37427189
DOI: 10.1097/MS9.0000000000000964 -
European Urology Oncology Jun 2021Management of newly diagnosed prostate cancer (PCa) is guided in part by accurate clinical staging. The role of imaging, including magnetic resonance imaging (MRI) and... (Review)
Review
The Role of Magnetic Resonance Imaging and Positron Emission Tomography/Computed Tomography in the Primary Staging of Newly Diagnosed Prostate Cancer: A Systematic Review of the Literature.
CONTEXT
Management of newly diagnosed prostate cancer (PCa) is guided in part by accurate clinical staging. The role of imaging, including magnetic resonance imaging (MRI) and positron emission tomography/computed tomography (PET/CT), in initial staging remains controversial.
OBJECTIVE
To systematically review the studies of MRI and/or PET/CT in the staging of newly diagnosed PCa with respect to tumor (T), nodal (N), and metastatic (M) staging (TNM staging).
EVIDENCE ACQUISITION
We performed a systematic review of the literature using MEDLINE and Web of Science databases between 2012 and 2020 following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement guidelines.
EVIDENCE SYNTHESIS
A total of 139 studies (83 on T, 47 on N, and 24 on M status) were included. Ninety-nine (71%) were retrospective, 39 (28%) were prospective, and one was a randomized controlled trial (RCT). Most studies on T staging examined MRI, while PET/CT was used primarily for N and M staging. Sensitivity for the detection of extraprostatic extension, seminal vesicle invasion, or lymph node invasion ranged widely. When imaging was incorporated into existing risk tools, gain in accuracy was observed in some studies, although these findings have not been replicated. For M staging, most favorable results were reported for prostate-specific membrane antigen (PSMA) PET/CT, which demonstrated significantly better performance than conventional imaging.
CONCLUSIONS
A variety of studies on modern imaging techniques for TNM staging in newly diagnosed PCa exist. For T and N staging, reported sensitivity of imaging modalities such as MRI or PET/CT varied widely due to data heterogeneity, small sample size, and low event rates resulting in large confidence intervals and a high level of uncertainty. Therefore, uniformity in data presentation and standardization on this topic are needed. The most promising technique for M staging, which was evaluated recently in an RCT, is PSMA-PET/CT.
PATIENT SUMMARY
We performed a systematic review of currently available imaging modalities to stage newly diagnosed prostate cancer. With respect to local tumor and lymph node assessment, performance of imaging ranged widely. However, prostate-specific membrane antigen positron emission tomography/computed tomography showed favorable results for the detection of distant metastases.
Topics: Humans; Lymph Nodes; Magnetic Resonance Imaging; Male; Neoplasm Staging; Positron Emission Tomography Computed Tomography; Prostatic Neoplasms; Randomized Controlled Trials as Topic
PubMed: 33272865
DOI: 10.1016/j.euo.2020.11.002 -
The Annals of Otology, Rhinology, and... Apr 2021In tissue engineering, biomaterials create a 3D scaffold for cell-to-cell adhesion, proliferation and tissue formation. Because of their similarity to extracellular...
OBJECTIVE
In tissue engineering, biomaterials create a 3D scaffold for cell-to-cell adhesion, proliferation and tissue formation. Because of their similarity to extracellular matrix and architectural adaptability, nanofibers are of particular interest in tissue engineering. Electrospinning is a well-documented technique for nanofiber production for tissue engineering scaffolds. Here we present literature on the applications of electrospinning in the field of otolaryngology.
REVIEW METHODS
A PubMed database search was performed to isolate articles published about applications of electrospun nanofibers for tissue engineering in otolaryngology. Study design, size, material tested, site of application within the head and neck, and outcomes were obtained for each study.
RESULTS
Almost all data on electrospinning in otolaryngology was published in the last 6 years (84%), highlighting its novelty. A total of 25 pre-clinical studies were identified: 9 in vitro studies, 5 in vivo animal studies, and 11 combination studies. Sites of application included: tracheal reconstruction (n = 16), tympanic membrane repair (n = 3), cranial nerve regeneration (n = 3), mastoid osteogenesis (n = 1) and ear/nose chondrogenesis (n = 2).
IMPLICATIONS FOR PRACTICE
Tissue engineering is a burgeoning field, with recent innovative applications in the field of otolaryngology. Electrospun nanofibers specifically have relevant applications in the field of otolaryngology, due in part to their similarity to native extracellular matrix, with emerging areas of interest being tympanic membrane repair, cranial nerve regeneration and tracheal reconstruction.
Topics: Biocompatible Materials; Electrochemical Techniques; Humans; Materials Testing; Nanofibers; Otolaryngology; Tissue Engineering; Tissue Scaffolds
PubMed: 32975429
DOI: 10.1177/0003489420959692 -
Frontiers in Plant Science 2022Vegetables are a distinct collection of plant-based foods that vary in nutritional diversity and form an important part of the healthy diet of the human being. Besides...
Vegetables are a distinct collection of plant-based foods that vary in nutritional diversity and form an important part of the healthy diet of the human being. Besides providing basic nutrition, they have great potential for boosting human health. The balanced consumption of vegetables is highly recommended for supplementing the human body with better nutrition density, dietary fiber, minerals, vitamins, and bioactive compounds. However, the production and quality of fresh vegetables are influenced directly or indirectly by exposure to high temperatures or heat stress (HS). A decline in quality traits and harvestable yield are the most common effects of HS among vegetable crops. Heat-induced morphological damage, such as poor vegetative growth, leaf tip burning, and rib discoloration in leafy vegetables and sunburn, decreased fruit size, fruit/pod abortion, and unfilled fruit/pods in beans, are common, often rendering vegetable cultivation unprofitable. Further studies to trace down the possible physiological and biochemical effects associated with crop failure reveal that the key factors include membrane damage, photosynthetic inhibition, oxidative stress, and damage to reproductive tissues, which may be the key factors governing heat-induced crop failure. The reproductive stage of plants has extensively been studied for HS-induced abnormalities. Plant reproduction is more sensitive to HS than the vegetative stages, and affects various reproductive processes like pollen germination, pollen load, pollen tube growth, stigma receptivity, ovule fertility and, seed filling, resulting in poorer yields. Hence, sound and robust adaptation and mitigation strategies are needed to overcome the adverse impacts of HS at the morphological, physiological, and biochemical levels to ensure the productivity and quality of vegetable crops. Physiological traits such as the stay-green trait, canopy temperature depression, cell membrane thermostability, chlorophyll fluorescence, relative water content, increased reproductive fertility, fruit numbers, and fruit size are important for developing better yielding heat-tolerant varieties/cultivars. Moreover, various molecular approaches such as omics, molecular breeding, and transgenics, have been proved to be useful in enhancing/incorporating tolerance and can be potential tools for developing heat-tolerant varieties/cultivars. Further, these approaches will provide insights into the physiological and molecular mechanisms that govern thermotolerance and pave the way for engineering "designer" vegetable crops for better health and nutritional security. Besides these approaches, agronomic methods are also important for adaptation, escape and mitigation of HS protect and improve yields.
PubMed: 35837452
DOI: 10.3389/fpls.2022.878498 -
Journal of Investigative and Clinical... Nov 2019Lichen planus is a common chronic, inflammatory, immune-mediated mucocutaneous disorder affecting the skin and mucosa. The role of mast cells in the genesis of lichen...
Lichen planus is a common chronic, inflammatory, immune-mediated mucocutaneous disorder affecting the skin and mucosa. The role of mast cells in the genesis of lichen planus has been debated. Establishing a definitive part played by mast cells and its degranulation would possibly provide a permanent, cost-effective treatment modality for oral lichen planus (OLP). This review aims to study the expression of mast cells qualitatively and quantitatively in OLP. The research questions were framed to assess the mast cell count, localization within the epithelium basement membrane zone and degranulation of mast cells. We performed a systematic search of PubMed, Medline, Cochrane and Web of Science. We found a total of 120 studies from which 12 were found suitable for the review. There is a marked increase in the number of mast cells in OLP. The mast cells were seen in increased numbers in the epithelial and connective tissue junction at areas of basement membrane disruption. There was also an increase in the degranulation of mast cells. It is evident that there is an increase in the mast cell number in lichen planus and its subsequent degranulation.
Topics: Cell Count; Connective Tissue; Epithelium; Humans; Lichen Planus, Oral; Mast Cells
PubMed: 31454180
DOI: 10.1111/jicd.12457 -
Alzheimer's Research & Therapy Mar 2024Pathogenic heterozygous mutations in the progranulin gene (GRN) are a key cause of frontotemporal dementia (FTD), leading to significantly reduced biofluid...
BACKGROUND
Pathogenic heterozygous mutations in the progranulin gene (GRN) are a key cause of frontotemporal dementia (FTD), leading to significantly reduced biofluid concentrations of the progranulin protein (PGRN). This has led to a number of ongoing therapeutic trials aiming to treat this form of FTD by increasing PGRN levels in mutation carriers. However, we currently lack a complete understanding of factors that affect PGRN levels and potential variation in measurement methods. Here, we aimed to address this gap in knowledge by systematically reviewing published literature on biofluid PGRN concentrations.
METHODS
Published data including biofluid PGRN concentration, age, sex, diagnosis and GRN mutation were collected for 7071 individuals from 75 publications. The majority of analyses (72%) had focused on plasma PGRN concentrations, with many of these (56%) measured with a single assay type (Adipogen) and so the influence of mutation type, age at onset, sex, and diagnosis were investigated in this subset of the data.
RESULTS
We established a plasma PGRN concentration cut-off between pathogenic mutation carriers and non-carriers of 74.8 ng/mL using the Adipogen assay based on 3301 individuals, with a CSF concentration cut-off of 3.43 ng/mL. Plasma PGRN concentration varied by GRN mutation type as well as by clinical diagnosis in those without a GRN mutation. Plasma PGRN concentration was significantly higher in women than men in GRN mutation carriers (p = 0.007) with a trend in non-carriers (p = 0.062), and there was a significant but weak positive correlation with age in both GRN mutation carriers and non-carriers. No significant association was seen with weight or with TMEM106B rs1990622 genotype. However, higher plasma PGRN levels were seen in those with the GRN rs5848 CC genotype in both GRN mutation carriers and non-carriers.
CONCLUSIONS
These results further support the usefulness of PGRN concentration for the identification of the large majority of pathogenic mutations in the GRN gene. Furthermore, these results highlight the importance of considering additional factors, such as mutation type, sex and age when interpreting PGRN concentrations. This will be particularly important as we enter the era of trials for progranulin-associated FTD.
Topics: Male; Humans; Female; Progranulins; Frontotemporal Dementia; Intercellular Signaling Peptides and Proteins; Virulence; Mutation; Membrane Proteins; Nerve Tissue Proteins
PubMed: 38539243
DOI: 10.1186/s13195-024-01420-z