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Kidney International Reports Jun 2024
The Conversion From Mycophenolic Acid to Mammalian Target of Rapamycin Inhibitor Reduces the Incidence of Cytomegalovirus Replication in Belatacept-Treated Kidney-Transplant Recipients.
PubMed: 38899171
DOI: 10.1016/j.ekir.2024.02.1433 -
International Journal of Hyperthermia :... 2024To evaluate the safety and efficacy of performing histotripsy through overlying gas-filled bowel in an swine model.
PURPOSE
To evaluate the safety and efficacy of performing histotripsy through overlying gas-filled bowel in an swine model.
METHODS
An model was created to simulate histotripsy treatment of solid organs through gas-filled bowel. Spherical 2.5 cm histotripsy treatments were performed in agar phantoms for each of five treatment groups: 1) control with no overlying bowel ( = 6), 2) bowel 0 cm above phantom ( = 6), 3) bowel 1 cm above phantom ( = 6), 4) bowel 2 cm above phantom ( = 6), and 5) bowel 0 cm above the phantom with increased treatment amplitude ( = 6). Bowel was inspected for gross and microscopic damage, and treatment zones were measured. A ray-tracing simulation estimated the percentage of therapeutic beam path blockage by bowel in each scenario.
RESULTS
All histotripsy treatments through partial blockage were successful (24/24). No visible or microscopic damage was observed to intervening bowel. Partial blockage resulted in a small increase in treatment volume compared to controls ( = 0.002 and = 0.036 for groups with bowel 0 cm above the phantom, > 0.3 for bowel 1 cm and 2 cm above the phantom). Gas-filled bowel was estimated to have blocked 49.6%, 35.0%, and 27.3% of the therapeutic beam at 0, 1, and 2 cm, respectively.
CONCLUSION
Histotripsy has the potential to be applied through partial gas blockage of the therapeutic beam path, as shown by this small bowel model. Further work in an survival model appears indicated.
Topics: Animals; Swine; Intestine, Small; Gases
PubMed: 38897626
DOI: 10.1080/02656736.2024.2369305 -
Biophysical Reports Jun 2024Magnetic fields have been shown to affect sensing, migration, and navigation in living organisms. However, the effects of magnetic fields on microorganisms largely...
Magnetic fields have been shown to affect sensing, migration, and navigation in living organisms. However, the effects of magnetic fields on microorganisms largely remain to be elucidated. We develop an open-source, 3D-printed magnetic field exposure device to perform experiments on well-mixed and spatially-structured microbial populations. This device is designed in AutoCAD, modeled in COMSOL, and validated using a Gaussmeter and experiments on the budding yeast Saccharomyces cerevisiae. We find that static magnetic field exposure slows the spatially-structured expansion of yeast mats that expands in two dimensions, but not yeast mats that expand in three dimensions, across the surface of semi-solid yeast extract-peptone-dextrose (YPD) agar media. We also find that magnetic fields do not affect the growth of planktonic yeast cells in well-mixed liquid YPD media. This study provides an adaptable device for performing controlled magnetic field experiments on microbes and advances our understanding of the effects of magnetic fields on fungi.
PubMed: 38897412
DOI: 10.1016/j.bpr.2024.100165 -
Frontiers in Medicine 2024Telomeres are located at chromosomal termini and function to maintain genomic integrity. Telomere dysfunction is a well-recognized contributor to aging and age-related...
BACKGROUND
Telomeres are located at chromosomal termini and function to maintain genomic integrity. Telomere dysfunction is a well-recognized contributor to aging and age-related diseases, such as prostate cancer. Since telomere length is highly heritable, we postulate that stromal cell telomere length in the tissue of a particular solid organ may generally reflect constitutive stromal cell telomere length in other solid organs throughout the body. Even with telomere loss occurring with each round of cell replication, in general, telomere length in prostate stromal cells in mid-life would still be correlated with the telomere length in stromal cells in other organs. Thus, we hypothesize that prostate stromal cell telomere length and/or telomere length variability is a potential indicator of the likelihood of developing future solid cancers, beyond prostate cancer, and especially lethal cancer.
METHODS
To explore this hypothesis, we conducted a cohort study analysis of 1,175 men who were surgically treated for prostate cancer and were followed for death, including from causes other than their prostate cancer.
RESULTS
In this cohort study with a median follow-up of 19 years, we observed that longer prostate stromal cell telomere length measured in tissue microarray spots containing prostate cancer was associated with an increased risk of death from other solid cancers. Variability in telomere length among these prostate stromal cells was possibly positively associated with risk of death from other solid cancers.
CONCLUSION
Studying the link between stromal cell telomere length and cancer mortality may be important for guiding the development of cancer interception and prevention strategies.
PubMed: 38895181
DOI: 10.3389/fmed.2024.1390769 -
Cancers May 2024Immunotherapy with immune checkpoint inhibitors (ICIs) has revolutionized contemporary oncology, presenting efficacy in various solid tumors and lymphomas. However, ICIs... (Review)
Review
Immunotherapy with immune checkpoint inhibitors (ICIs) has revolutionized contemporary oncology, presenting efficacy in various solid tumors and lymphomas. However, ICIs may potentially overstimulate the immune system, leading to immune-related adverse events (irAEs). IrAEs may affect multiple organs, such as the colon, stomach, small intestine, kidneys, skin, lungs, joints, liver, lymph nodes, bone marrow, brain, heart, and endocrine glands (e.g., pancreas, thyroid, or adrenal glands), exhibiting autoimmune inflammation. F-fluorodeoxyglucose positron emission tomography/computed tomography (F-FDG PET/CT) is commonly used in oncology for staging and assessment of therapy responses, but it may also serve as a tool for detecting irAEs. This review aims to present various patterns of metabolic activation associated with irAEs due to ICI treatment, identifiable through F-FDG PET/CT. It describes the advantages of early detection of irAEs, but also presents the challenges in differentiating them from tumor progression. It also delves into aspects of molecular response assessment within the context of pseudoprogression and hyperprogression, along with typical imaging findings related to these phenomena. Lastly, it summarizes the role of functional PET imaging in oncological immunotherapy, speculating on its future significance and limitations.
PubMed: 38893111
DOI: 10.3390/cancers16111990 -
Journal of Clinical Medicine May 2024Non-ideal donors provide acceptable allografts and may expand the donor pool. This study evaluates donor utilization across solid organs over 15-years in the United...
Non-ideal donors provide acceptable allografts and may expand the donor pool. This study evaluates donor utilization across solid organs over 15-years in the United States. We analyzed the OPTN STAR database to identify potential donors across three donor eras: 2005-2009, 2010-2014, and 2015-2019. Donors were analyzed by a composite Donor Utilization Score (DUS), comprised of donor age and comorbidities. Outcomes of interest were overall and organ-specific donor utilization. Descriptive analyses and multivariable logistic regression modeling were performed. -values < 0.01 considered significant. Of 132,465 donors, 32,710 (24.7%) were identified as non-ideal donors (NID), based on a DUS ≥ 3. Compared to ideal donors (ID), NID were older (median 56 years, IQR 51-64 years vs. 35 years, 22-48 years, < 0.001) and more frequently female (44.3% vs. 39.1%, < 0.001), Black (22.1% vs. 14.6%, < 0.001) and obese (60.7% vs. 19.6%, < 0.001). The likelihood of overall DBD utilization from NID increased from Era 1 to Era 2 (OR 1.227, 95% CI 1.123-1.341, < 0.001) and Era 3 (OR 1.504, 1.376-1.643, < 0.001), while DCD donor utilization in NID was not statistically different across Eras. Compared to Era 1, the likelihood of DBD utilization from NID for kidney transplantation was lower in Era 2 (OR 0.882, 0.822-0.946) and Era 3 (OR 0.938, 0.876-1.004, = 0.002). The likelihood of NID utilization increased in Era 3 compared to Era 1 for livers (OR 1.511, 1.411-1.618, < 0.001), hearts (OR 1.623, 1.415-1.862, < 0.001), and lungs (OR 2.251, 2.011-2.520, < 0.001). Using a universal definition of NID across organs, NID donor utilization is increasing; however, use of DUS may improve resource utilization in identifying donors at highest likelihood for multi-organ donation.
PubMed: 38892982
DOI: 10.3390/jcm13113271 -
Journal of Clinical Medicine May 2024B and T regulatory cells, also known as Bregs and Tregs, are involved in kidney transplantation. The purpose of this study is to monitor changes in the frequency and...
Evaluation of Regulatory B Cell Subpopulations CD24++CD38++, CD24++CD27+, Plasmablasts and Their Correlation with T Regs CD3+CD4+CD25+FOXP3+ in Dialysis Patients and Early Post-Transplant Rejection-Free Kidney Recipients.
B and T regulatory cells, also known as Bregs and Tregs, are involved in kidney transplantation. The purpose of this study is to monitor changes in the frequency and absolute numbers of Tregs (CD3+CD4+CD25+FoxP3+), transitional Bregs (tBregs) (CD24++CD38++), memory Bregs (mBregs) (CD24++CD27+), and plasmablasts before (T0) and six months (T6) after transplantation. Additionally, we aim to investigate any correlation between Tregs and tBregs, mBregs, or plasmablasts and their relationship with graft function. Flow cytometry was used to immunophenotype cells from 50 kidney recipients who did not experience rejection. Renal function was assessed using the estimated glomerular filtration rate (eGFR). At T6, there was a significant decrease in the frequency of Tregs, plasmablasts, and tBregs, as well as in the absolute number of tBregs. The frequency of mBregs, however, remained unchanged. Graft function was found to have a positive correlation with the frequency of tBregs and plasmablasts. A significant correlation was observed between the frequency and absolute number of tBregs only when the eGFR was greater than 60 but not at lower values. At an eGFR greater than 60, there was a positive correlation between the absolute numbers of Tregs and mBregs but not between Tregs and tBregs. No correlation was observed for any cell population in dialysis patients. The data show a correlation between the frequency and absolute number of tBregs and the absolute number of Tregs and mBregs with good renal function in the early post-transplant period.
PubMed: 38892795
DOI: 10.3390/jcm13113080 -
International Journal of Molecular... Jun 2024The autonomic nervous system plays an integral role in motion and sensation as well as the physiologic function of visceral organs. The nervous system additionally plays... (Review)
Review
The autonomic nervous system plays an integral role in motion and sensation as well as the physiologic function of visceral organs. The nervous system additionally plays a key role in primary liver diseases. Until recently, however, the impact of nerves on cancer development, progression, and metastasis has been unappreciated. This review highlights recent advances in understanding neuroanatomical networks within solid organs and their mechanistic influence on organ function, specifically in the liver and liver cancer. We discuss the interaction between the autonomic nervous system, including sympathetic and parasympathetic nerves, and the liver. We also examine how sympathetic innervation affects metabolic functions and diseases like nonalcoholic fatty liver disease (NAFLD). We also delve into the neurobiology of the liver, the interplay between cancer and nerves, and the neural regulation of the immune response. We emphasize the influence of the neuroimmune axis in cancer progression and the potential of targeted interventions like neurolysis to improve cancer treatment outcomes, especially for hepatocellular carcinoma (HCC).
Topics: Humans; Liver Neoplasms; Neuroimmunomodulation; Animals; Carcinoma, Hepatocellular; Liver; Non-alcoholic Fatty Liver Disease; Autonomic Nervous System
PubMed: 38892423
DOI: 10.3390/ijms25116237 -
Open Forum Infectious Diseases Jun 2024Mucormycosis is an emerging disease primarily affecting the immunocompromised host, but scarce evidence is available for solid organ transplant recipients (SOTRs). We... (Review)
Review
Mucormycosis is an emerging disease primarily affecting the immunocompromised host, but scarce evidence is available for solid organ transplant recipients (SOTRs). We systematically reviewed 183 cases occurring in SOTRs, exploring epidemiology, clinical characteristics, causative pathogens, therapeutic approaches, and outcomes. Kidney transplants accounted for half of the cases, followed by heart (18.6%), liver (16.9%), and lung (10.4%). Diagnosis showed a dichotomous distribution, with 63.7% of cases reported within 100 days of transplantation and 20.6% occurring at least 1 year after transplant. The 90-day and 1-year mortality rates were 36.3% and 63.4%, respectively. Disseminated disease had the highest mortality at both time points (75% and 93%). Treatment with >3 immunosuppressive drugs showed a significant impact on 90-day mortality (odds ratio [OR], 2.33; 95% CI, 1.02-5.66; = .0493), as did a disseminated disease manifestation (OR, 8.23; 95% CI, 2.20-36.71; = .0027) and the presence of diabetes (OR, 2.35; 95% CI, 1.01-5.65; = .0497). Notably, prophylaxis was administered to 12 cases with amphotericin B. Further investigations are needed to validate these findings and to evaluate the potential implementation of prophylactic regimens in SOTRs at high risk.
PubMed: 38887489
DOI: 10.1093/ofid/ofae043