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Open Forum Infectious Diseases Jun 2024Among solid organ transplant recipients taking belatacept, 15% developed invasive fungal diseases. The most common invasive fungal diseases were aspergillosis (56%) and...
An Unexpectedly High Incidence of Invasive Fungal Diseases in Solid Organ Transplant Recipients Taking Belatacept for Organ Rejection Prophylaxis: A Single-Center Retrospective Cohort Study.
Among solid organ transplant recipients taking belatacept, 15% developed invasive fungal diseases. The most common invasive fungal diseases were aspergillosis (56%) and candidiasis (22%). The infected cohort was more likely to receive basiliximab, undergo lung transplantation, or identify as White. Higher rates of aspergillosis were seen in this lung cohort than previously reported.
PubMed: 38887477
DOI: 10.1093/ofid/ofae158 -
Journal For Immunotherapy of Cancer Jun 2024Immune checkpoint inhibitors (ICIs) can elicit anticancer immune responses, but predictive biomarkers are needed. We measured programmed death ligand 1 (PD-L1)...
Exploring the predictive potential of programmed death ligand 1 expression in healthy organs and lymph nodes as measured by F-BMS986-192 PET: pooled analysis of data from four solid tumor types.
INTRODUCTION
Immune checkpoint inhibitors (ICIs) can elicit anticancer immune responses, but predictive biomarkers are needed. We measured programmed death ligand 1 (PD-L1) expression in organs and lymph nodes using F-BMS-986192 positron emission tomography (PET)-imaging and looked for correlations with response and immune-related adverse events.
METHODS
Four F-BMS-986192 PET studies in patients with melanoma, lung, pancreatic and oral cancer, receiving ICI treatment, were combined. Imaging data (organ standardized uptake value (SUV), lymph node SUV) and clinical data (response to treatment and incidence of immune-related adverse events) were extracted.
RESULTS
Baseline PD-L1 uptake in the spleen was on average higher in non-responding patients than in responders (spleen SUV 16.1±4.4 vs 12.5±3.4, p=0.02). This effect was strongest in lung cancer, and not observed in oral cancer. In the oral cancer cohort, benign tumor-draining lymph nodes (TDLNs) had higher PD-L1 uptake (SUV 3.3 IQR 2.5-3.9) compared with non-TDLNs (SUV 1.8, IQR 1.4-2.8 p=0.04). Furthermore, in the same cohort non-responders showed an increase in PD-L1 uptake in benign TDLNs on-treatment with ICIs (+15%), while for responders the PD-L1 uptake decreased (-11%). PD-L1 uptake did not predict immune-related adverse events, though elevated thyroid uptake on-treatment correlated with pre-existing thyroid disease or toxicity.
CONCLUSION
PD-L1 PET uptake in the spleen is a potential negative predictor of response to ICIs. On-treatment with ICIs, PD-L1 uptake in benign TDLNs increases in non-responders, while it decreases in responders, potentially indicating a mechanism for resistance to ICIs in patients with oral cancer.
Topics: Humans; B7-H1 Antigen; Lymph Nodes; Positron-Emission Tomography; Male; Female; Neoplasms; Immune Checkpoint Inhibitors; Middle Aged; Aged
PubMed: 38886117
DOI: 10.1136/jitc-2024-008899 -
Annals of Surgery Open : Perspectives... Mar 2024Intent-to-treat analysis follows patients from listing to death, regardless of their transplant status, and aims to provide a more holistic scope of the progress made in...
OBJECTIVE
Intent-to-treat analysis follows patients from listing to death, regardless of their transplant status, and aims to provide a more holistic scope of the progress made in adult solid-organ transplantation.
BACKGROUND
Many studies have shown progress in waitlist and post-transplant survival for adult kidney, liver, heart, and lung transplants, but there is a need to provide a more comprehensive perspective of transplant outcomes for patients and their families.
METHODS
Univariable and multivariable Cox regression analyses were used to analyze factors contributing to intent-to-treat survival in 813,862 adults listed for kidney, liver, heart, and lung transplants. The Kaplan-Meier method was used to examine changes in waitlist, post-transplant, and intent-to-treat survival. Transplantation rates were compared using χ tests.
RESULTS
Intent-to-treat survival has steadily increased for liver, heart, and lung transplants. The percentage of patients transplanted within 1 year significantly increased for heart (57.4% from 52.9%) and lung (73.5% from 33.2%). However, the percentage of patients transplanted within 1 year significantly decreased from 35.8% to 21.2% for kidney transplant. Notably, intent-to-treat survival has decreased for kidneys despite increases in waitlist and post-transplant survival, likely because of the decreased transplant rate.
CONCLUSION
Intent-to-treat survival steadily improved for liver, heart, and lung transplant over the 30-year study period. Continued advancements in allocation policy, immunosuppression, and improved care of patients on the waitlist may contribute to further progress in outcomes of all organs, but the increasing discrepancy in supply and demand of donor kidneys is alarming and has impeded the progress of kidney intent-to-treat survival.
PubMed: 38883932
DOI: 10.1097/AS9.0000000000000383 -
Cureus May 2024Pericardial effusion, a clinical condition characterized by an abnormal accumulation of fluid in the pericardial cavity, has multiple etiological factors. One of the...
Pericardial effusion, a clinical condition characterized by an abnormal accumulation of fluid in the pericardial cavity, has multiple etiological factors. One of the prominent causes is malignant effusion. The patient is a 69-year-old female with a past medical history of Crohn's disease, melanoma status post-resection, and osteoarthritis. She presented with complaints of abdominal discomfort, shortness of breath on exertion, and lower extremity swelling for the past 2-3 days. She was recently discharged four days before this visit after being treated for a viral infection. A physical examination was significant for tachycardia, muffled heart sounds, abdominal distention, and bilateral lower extremity swelling. Labs were in the normal range except for elevated liver enzymes and sodium of 130 mmol/L. A chest X-ray revealed a small bilateral effusion; a bedside echocardiogram showed an ejection fraction greater than 70% and a large pericardial effusion >2 cm, consistent with cardiac tamponade. Emergent pericardiocentesis was performed with the drainage of 250 milliliters of hemorrhagic fluid, which was sent for diagnostic studies. Post-procedure echo on the next day showed an EF of 35-40% and no recurrent pericardial effusion. The workup for connective tissue disease was negative except for elevated antinuclear antibodies (ANA). CT of the abdomen and pelvis revealed gastric wall thickening with no solid organ mass. Her pericardial fluid studies were consistent with exudative etiology and positive for atypical lymphoid cells, leading to the diagnosis of diffuse large B-cell lymphoma. Diffuse large B-cell lymphoma is the most common type of non-Hodgkin lymphoma. Malignant pericardial effusion is common due to solid organ malignancy; however, it is rare with diffuse large B cell lymphoma (DLBCL). We present an intriguing case where pericardial effusion was the precursor to the eventual diagnosis of DLBCL, highlighting the complexity and diverse manifestations of this lymphoma subtype.
PubMed: 38882999
DOI: 10.7759/cureus.60418 -
Journal of Graduate Medical Education Jun 2024
Topics: Humans; Internship and Residency; Fellowships and Scholarships; Education, Medical, Graduate; Clinical Competence
PubMed: 38882419
DOI: 10.4300/JGME-D-23-00541.1 -
Mediastinum (Hong Kong, China) 2024The mediastinum is a complex, heterogeneous area, which leads vertically across the thoracic cavity between the bilateral mediastinal pleurae, connecting the head and... (Review)
Review
BACKGROUND AND OBJECTIVE
The mediastinum is a complex, heterogeneous area, which leads vertically across the thoracic cavity between the bilateral mediastinal pleurae, connecting the head and neck region with the thoracic cavity. Different classifications have been published to differentiate between the so-called mediastinal compartments while the most used classification surely is the 4-compartments Gray`s classification, dividing it into the superior, anterior, middle and posterior mediastinum. Mediastinal abnormalities include infections (mediastinitis) and solid or cystic mediastinal masses. These masses can be divided into benign and malignant lesions originating from mediastinal structures/organs or represent manifestations of metastatic disease, often metastatic non-small cell lung cancer (NSCLC). This review aims to explore the different mediastinal pathologies along with indications and surgical approaches.
METHODS
We performed literature research in PubMed, MEDLINE, Embase, CENTRAL, and CINAHL databases. Only papers written in English were included.
KEY CONTENT AND FINDINGS
Depending on the indication for surgical intervention and the localization of the pathology, surgical approach may differ immensely. Mediastinal staging of lung cancer, primary lesions of the mediastinum, mediastinitis and traumatic mediastinal injuries display the most frequent indications for mediastinal surgery. Surgical approaches trend towards minimally invasive, video- or robotic-assisted techniques and are becoming increasingly refined to adapt to the special characteristics of the mediastinum. However, certain indications still require open access for best possible mediastinal exposure or oncological reasons.
CONCLUSIONS
To guide optimal surgical approach selection to the mediastinum, the following overview will present all published surgical approaches to the mediastinum and discuss their practical relevance and indications aiming to help surgeons in the management of patients with mediastinal pathologies who should undergo surgery.
PubMed: 38881816
DOI: 10.21037/med-23-71 -
Transplant International : Official... 2024
Topics: Humans; Immunosuppressive Agents; Organ Transplantation; Clinical Trials as Topic; Graft Rejection
PubMed: 38881802
DOI: 10.3389/ti.2024.13211 -
Microbial Biotechnology Jun 2024Carboxylic ester hydrolases with the capacity to degrade polyesters are currently highly sought after for their potential use in the biological degradation of PET and...
Carboxylic ester hydrolases with the capacity to degrade polyesters are currently highly sought after for their potential use in the biological degradation of PET and other chemically synthesized polymers. Here, we describe MarCE, a carboxylesterase family protein identified via genome mining of a Maribacter sp. isolate from the marine sponge Stelligera stuposa. Based on phylogenetic analysis, MarCE and its closest relatives belong to marine-associated genera from the Cytophaga-Flavobacterium-Bacteroides taxonomic group and appear evolutionarily distinct to any homologous carboxylesterases that have been studied to date in terms of structure or function. Molecular docking revealed putative binding of BHET, a short-chain PET derivative, onto the predicted MarCE three-dimensional structure. The synthetic ester-degrading activity of MarCE was subsequently confirmed by MarCE-mediated hydrolysis of 2 mM BHET substrate, indicated by the release of its breakdown products MHET and TPA, which were measured, respectively, as 1.28 and 0.12 mM following 2-h incubation at 30°C. The findings of this study provide further insight into marine carboxylic ester hydrolases, which have the potential to display unique functional plasticity resulting from their adaptation to complex and fluctuating marine environmentsw.
Topics: Carboxylesterase; Phylogeny; Animals; Porifera; Esters; Gene Expression; Molecular Docking Simulation; Aquatic Organisms
PubMed: 38881500
DOI: 10.1111/1751-7915.14479 -
BMC Plant Biology Jun 2024Epidermal patterning factor / -like (EPF/EPFL) gene family encodes a class of cysteine-rich secretory peptides, which are widelyfound in terrestrial plants.Multiple...
BACKGROUND
Epidermal patterning factor / -like (EPF/EPFL) gene family encodes a class of cysteine-rich secretory peptides, which are widelyfound in terrestrial plants.Multiple studies has indicated that EPF/EPFLs might play significant roles in coordinating plant development and growth, especially as the morphogenesis processes of stoma, awn, stamen, and fruit skin. However, few research on EPF/EPFL gene family was reported in Gossypium.
RESULTS
We separately identified 20 G. raimondii, 24 G. arboreum, 44 G. hirsutum, and 44 G. barbadense EPF/EPFL genes in the 4 representative cotton species, which were divided into four clades together with 11 Arabidopsis thaliana, 13 Oryza sativa, and 17 Selaginella moellendorffii ones based on their evolutionary relationships. The similar gene structure and common motifs indicated the high conservation among the EPF/EPFL members, while the uneven distribution in chromosomes implied the variability during the long-term evolutionary process. Hundreds of collinearity relationships were identified from the pairwise comparisons of intraspecifc and interspecific genomes, which illustrated gene duplication might contribute to the expansion of cotton EPF/EPFL gene family. A total of 15 kinds of cis-regulatory elements were predicted in the promoter regions, and divided into three major categories relevant to the biological processes of development and growth, plant hormone response, and abiotic stress response. Having performing the expression pattern analyses with the basic of the published RNA-seq data, we found most of GhEPF/EPFL and GbEPF/EPFL genes presented the relatively low expression levels among the 9 tissues or organs, while showed more dramatically different responses to high/low temperature and salt or drought stresses. Combined with transcriptome data of developing ovules and fibers and quantitative Real-time PCR results (qRT-PCR) of 15 highly expressed GhEPF/EPFL genes, it could be deduced that the cotton EPF/EPFL genes were closely related with fiber development. Additionally, the networks of protein-protein interacting among EPF/EPFLs concentrated on the cores of GhEPF1 and GhEPF7, and thosefunctional enrichment analyses indicated that most of EPF/EPFLs participate in the GO (Gene Ontology) terms of stomatal development and plant epidermis development, and the KEGG (Kyoto Encyclopedia of Genes and Genomes) pathways of DNA or base excision repair.
CONCLUSION
Totally, 132 EPF/EPFL genes were identified for the first time in cotton, whose bioinformatic analyses of cis-regulatory elements and expression patterns combined with qRT-PCR experiments to prove the potential functions in the biological processes of plant growth and responding to abiotic stresses, specifically in the fiber development. These results not only provide comprehensive and valuable information for cotton EPF/EPFL gene family, but also lay solid foundation for screening candidate EPF/EPFL genes in further cotton breeding.
Topics: Gossypium; Multigene Family; Plant Proteins; Phylogeny; Gene Expression Regulation, Plant; Genome, Plant; Genes, Plant; Genome-Wide Association Study; Gene Expression Profiling; Protein Interaction Maps
PubMed: 38877405
DOI: 10.1186/s12870-024-05262-7 -
Cancer Medicine Jun 2024Secreted Frizzled-Related Protein 5 (SFRP5) modulates Wnt signalling pathways, affecting diverse biological processes. We assessed the diagnostic and prognostic value of...
BACKGROUND
Secreted Frizzled-Related Protein 5 (SFRP5) modulates Wnt signalling pathways, affecting diverse biological processes. We assessed the diagnostic and prognostic value of circulating SFRP5 (cSFRP5) in colorectal cancer (CRC) METHODS: Plasma cSFRP5 concentrations were measured using enzyme-linked immunosorbent assay (ELISA) in healthy donors (n = 133), individuals diagnosed with CRC (n = 449), colorectal polyps (n = 85), and medical conditions in other organs including cancer, inflammation, and benign states (n = 64).
RESULTS
Patients with CRC, polyps, and other conditions showed higher cSFRP5 levels than healthy individuals (p < 0.0001). Receiver operating characteristic curves comparing healthy donors with medical conditions, polyps and CRC were 0.814 (p < 0.0001), 0.763 (p < 0.0001) and 0.762 (p < 0.0001), respectively. In CRC, cSFRP5 correlated with patient age (p < 0.0001), tumour stage (p < 0.0001), and histological differentiation (p = 0.0273). Levels, adjusted for patient age, sex, plasma age and collection institution, peaked in stage II versus I (p < 0.0001), III (p = 0.0002) and IV (p < 0.0001), were lowest in stage I versus III (p = 0.0002) and IV (p = 0.0413), with no difference between stage III and IV. Elevated cSFRP5 levels predicted longer overall survival in stages II-III CRC (univariate: HR 1.82, 95% CI: 1.02-3.26, p = 0.024; multivariable: HR 2.34, 95% CI: 1.12-4.88, p = 0.015).
CONCLUSION
This study confirms cSFRP5 levels are elevated in CRC compared to healthy control and reveals a correlation between elevated cSFRP5 and overall survival in stages II-III disease.
Topics: Humans; Colorectal Neoplasms; Male; Female; Prognosis; Middle Aged; Aged; Biomarkers, Tumor; Adaptor Proteins, Signal Transducing; Adult; Neoplasm Staging; ROC Curve; Aged, 80 and over; Case-Control Studies
PubMed: 38872420
DOI: 10.1002/cam4.7352