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Frontiers in Immunology 2024Chronic inflammatory enteropathy (CIE) is a common condition in dogs causing recurrent or persistent gastrointestinal clinical signs. Pathogenesis is thought to involve...
Chronic inflammatory enteropathy (CIE) is a common condition in dogs causing recurrent or persistent gastrointestinal clinical signs. Pathogenesis is thought to involve intestinal mucosal inflammatory infiltrates, but histopathological evaluation of intestinal biopsies from dogs with CIE fails to guide treatment, inform prognosis, or correlate with clinical remission. We employed single-cell RNA sequencing to catalog and compare the diversity of cells present in duodenal mucosal endoscopic biopsies from 3 healthy dogs and 4 dogs with CIE. Through characterization of 35,668 cells, we identified 31 transcriptomically distinct cell populations, including T cells, epithelial cells, and myeloid cells. Both healthy and CIE samples contributed to each cell population. T cells were broadly subdivided into GZMA (putatively annotated as tissue resident) and IL7R (putatively annotated as non-resident) T cell categories, with evidence of a skewed proportion favoring an increase in the relative proportion of IL7R T cells in CIE dogs. Among the myeloid cells, neutrophils from CIE samples exhibited inflammatory (SOD2 and IL1A) gene expression signatures. Numerous differentially expressed genes were identified in epithelial cells, with gene set enrichment analysis suggesting enterocytes from CIE dogs may be undergoing stress responses and have altered metabolic properties. Overall, this work reveals the previously unappreciated cellular heterogeneity in canine duodenal mucosa and provides new insights into molecular mechanisms which may contribute to intestinal dysfunction in CIE. The cell type gene signatures developed through this study may also be used to better understand the subtleties of canine intestinal physiology in health and disease.
Topics: Animals; Dogs; Duodenum; Single-Cell Analysis; Dog Diseases; Transcriptome; Gene Expression Profiling; Intestinal Mucosa; Chronic Disease; Male; Female; T-Lymphocytes
PubMed: 38933260
DOI: 10.3389/fimmu.2024.1397590 -
Pulmonary Circulation Apr 2024Pulmonary hypertension (PH) is a severe medical condition with a number of treatment options, the majority of which are introduced without consideration of the... (Review)
Review
Pulmonary hypertension (PH) is a severe medical condition with a number of treatment options, the majority of which are introduced without consideration of the underlying mechanisms driving it within an individual and thus a lack of tailored approach to treatment. The one exception is a patient presenting with apparent pulmonary arterial hypertension and shown to have vaso-responsive disease, whose clinical course and prognosis is significantly improved by high dose calcium channel blockers. PH is however characterized by a relative abundance of available data from patient cohorts, ranging from molecular data characterizing gene and protein expression in different tissues to physiological data at the organ level and clinical information. Integrating available data with mechanistic information at the different scales into computational models suggests an approach to a more personalized treatment of the disease using model-based optimization of interventions for individual patients. That is, constructing digital twins of the disease, customized to a patient, promises to be a key technology for personalized medicine, with the aim of optimizing use of existing treatments and developing novel interventions, such as new drugs. This article presents a perspective on this approach in the context of a review of existing computational models for different aspects of the disease, and it lays out a roadmap for a path to realizing it.
PubMed: 38933181
DOI: 10.1002/pul2.12392 -
Frontiers in Medicine 2024Intestinal ischemia/reperfusion is a prevalent pathological process that can result in intestinal dysfunction, bacterial translocation, energy metabolism disturbances,... (Review)
Review
Intestinal ischemia/reperfusion is a prevalent pathological process that can result in intestinal dysfunction, bacterial translocation, energy metabolism disturbances, and subsequent harm to distal tissues and organs via the circulatory system. Acute lung injury frequently arises as a complication of intestinal ischemia/reperfusion, exhibiting early onset and a grim prognosis. Without appropriate preventative measures and efficacious interventions, this condition may progress to acute respiratory distress syndrome and elevate mortality rates. Nonetheless, the precise mechanisms and efficacious treatments remain elusive. This paper synthesizes recent research models and pertinent injury evaluation criteria within the realm of acute lung injury induced by intestinal ischemia/reperfusion. The objective is to investigate the roles of pathophysiological mechanisms like oxidative stress, inflammatory response, apoptosis, ferroptosis, and pyroptosis; and to assess the strengths and limitations of current therapeutic approaches for acute lung injury stemming from intestinal ischemia/reperfusion. The goal is to elucidate potential targets for enhancing recovery rates, identify suitable treatment modalities, and offer insights for translating fundamental research into clinical applications.
PubMed: 38933104
DOI: 10.3389/fmed.2024.1399744 -
World Journal of Nuclear Medicine Jun 2024Differentiated thyroid carcinoma (DTC) usually is slow growing and carries a good prognosis. It most commonly tends to spread locally to regional lymph nodes in 20 to...
Unusual Metastatic Sites and Radioiodine Uptake in Patients of Differentiated Thyroid Carcinoma with Atypical Clinical Presentations: Utilization of I-Whole-Body Scintigraphy with Regional SPECT/CT.
Differentiated thyroid carcinoma (DTC) usually is slow growing and carries a good prognosis. It most commonly tends to spread locally to regional lymph nodes in 20 to 60% of patients. The presence of distant metastasis impacts overall survival and prognosis. The lungs, bones, and the brain are typically involved in distant sites with less common metastatic sites that include the liver, kidney, skeletal muscle, adrenal glands, bladder, and skin. These unusual sites are rare and pose a diagnostic challenge and impact clinical decision-making to a great extent. The radioiodine I whole-body scintigraphy with single-photon emission computed tomography/computed tomography can provide a thorough investigation of unusual sites of uptake leading to diagnosis of these metastases. We present a case series of DTC showing unusual sites of metastasis and/or radioiodine uptake in urinary bladder, in the third metacarpal bone of left hand and lastly in the forearm at postoperative hypertrophic scar area.
PubMed: 38933072
DOI: 10.1055/s-0044-1779750 -
World Journal of Nuclear Medicine Jun 2024Neuroendocrine tumors (NETs) are a rare spectrum of neoplasms that are characterized by neuroendocrine and neural differentiation. The treatment can be challenging in...
Neuroendocrine tumors (NETs) are a rare spectrum of neoplasms that are characterized by neuroendocrine and neural differentiation. The treatment can be challenging in view of the heterogeneity in differentiation and behavior. Primary renal origin NETs are rare and only a few cases have been reported in the literature. There is limited knowledge on their presentation and response to various lines of treatment. We report a case of a patient with a metastatic renal NET from a rare histological subtype of large cell neuroendocrine carcinoma, known to cause aggressive disease with poor prognosis. A multimodality treatment approach was followed. In spite of surgical management and second-line chemotherapy, the disease progressed. The patient subsequently received peptide receptor radionuclide therapy (PRRNT) using lutetium-177 DOTATATE, following which the patient demonstrated a remarkable clinical and radiological response and is stable to date. In a rare tumor with poor prognosis, the relevance of theranostics and the efficacy of targeted therapies like PRRNT are noteworthy.
PubMed: 38933067
DOI: 10.1055/s-0044-1785461 -
Frontiers in Cardiovascular Medicine 2024The long-term impact of type 2 diabetes mellitus (T2DM) after an acute myocardial infarction (AMI) has not been thoroughly investigated yet. This study aimed to assess...
OBJECTIVE
The long-term impact of type 2 diabetes mellitus (T2DM) after an acute myocardial infarction (AMI) has not been thoroughly investigated yet. This study aimed to assess the long-term impact of T2DM after AMI.
RESEARCH DESIGN AND METHODS
We analyzed the data of three nationwide observational studies from the French Registry of Acute ST-elevation and non-ST-elevation Myocardial Infarction (FAST-MI) program, conducted over a 1-month period in 2005, 2010, and 2015. Patients presenting T2DM were classified as diabetic, and patients presenting type 1 diabetes mellitus were excluded. We identified factors related to all-cause death at 1-year follow-up and divided 1,897 subjects into two groups, paired based on their estimated 1-year probability of death as determined by a logistic regression model.
RESULTS
A total of 9,181 AMI patients were included in the analysis, among them 2,038 (22.2%) had T2DM. Patients with diabetes were significantly older (68.2 ± 12.0 vs. 63.8 ± 14.4, < 0.001) and had a higher prevalence of a prior history of percutaneous coronary intervention (PCI), coronary artery bypass grafting (CABG), or heart failure (22.5% vs. 13.0%, 7.1% vs. 3.1% and 6.7 vs. 3.8% respectively, < 0.001 for all). Even after matching two groups of 1,897 patients based on propensity score for their 1-year probability of death, diabetes remained associated with long-term mortality, with an HR of 1.30, 95%CI (1.17-1.45), < 0.001.
CONCLUSIONS
T2DM has an adverse impact on long-term survival after myocardial infarction. Independently of the risk of short-term mortality, patients with diabetes who survived an AMI have a 30% higher risk of long-term mortality.
PubMed: 38932992
DOI: 10.3389/fcvm.2024.1401569 -
Frontiers in Cardiovascular Medicine 2024Severe tricuspid regurgitation (TR) causing cyanosis with patent foramen ovale (PFO) and right-to-left atrial shunting requires a precise diagnosis for optimal therapy....
BACKGROUND
Severe tricuspid regurgitation (TR) causing cyanosis with patent foramen ovale (PFO) and right-to-left atrial shunting requires a precise diagnosis for optimal therapy. Tricuspid valve prolapse (TVP) can lead to TR and is sometimes overlooked, especially in complex cases with factors like pulmonary hypertension (PH). We present an infant with cyanosis and profound TR after high-altitude exposure, initially misattributed to PH but found to be primarily due to spontaneous chordae tendineae rupture and TVP. This case underscores the challenges in diagnosing TR-induced cyanosis.
CASE PRESENTATION
The 3-month-old infant rapidly developed cyanosis, hypoxemia, right atrial enlargement, severe tricuspid regurgitation (TR), and patent foramen ovale (PFO) shunting after high-altitude exposure. Although echocardiography revealed tricuspid valve prolapse (TVP), initial consideration linked TR and right-to-left shunting to pulmonary hypertension (PH) due to the temporal correlation with rapid altitude exposure. Despite hemodynamic stability and the absence of respiratory distress after respiratory support and combined PH medication therapy, the persistent hypoxemia did not reverse as expected. This treatment outcome and repeated echocardiograms reminded us that TR was primarily caused by TVP rather than PH alone. Intraoperative exploration confirmed that TVP was caused by a rupture of TV chordae tendineae and anterior papillary muscle head, and the chordae tendineae/papillary muscle connection was reconstructed. After surgery, this patient was noncyanotic with an excellent long-term prognosis, a trivial TR with normal TV function being observed echocardiographically.
CONCLUSIONS
TR-induced cyanosis can be not only a consequence of PH and right-sided heart dilation but also a primary condition. Repetitive reassessment should be undertaken with caution, particularly when patients are not improving on therapy in the setting of conditions known to predisposition to secondary TR. Since TVP caused by rupture of the chordae or papillary muscles is rare but fatal in children, early diagnosis is clinically substantial to proper management and satisfactory long-term outcomes.
PubMed: 38932987
DOI: 10.3389/fcvm.2024.1335218 -
Frontiers in Molecular Neuroscience 2024Stroke is a devastating disease with high morbidity, disability, and mortality, among which ischemic stroke is more common. However, there is still a lack of effective... (Review)
Review
Stroke is a devastating disease with high morbidity, disability, and mortality, among which ischemic stroke is more common. However, there is still a lack of effective methods to improve the prognosis and reduce the incidence of its complications. At present, there is evidence that peripheral organs are involved in the inflammatory response after stroke. Moreover, the interaction between central and peripheral inflammation includes the activation of resident and peripheral immune cells, as well as the activation of inflammation-related signaling pathways, which all play an important role in the pathophysiology of stroke. In this review, we discuss the mechanisms of inflammatory response after ischemic stroke, as well as the interactions through circulatory pathways between peripheral organs (such as the gut, heart, lung and spleen) and the brain to mediate and regulate inflammation after ischemic stroke. We also propose the potential role of meningeal lymphatic vessels (MLVs)-cervical lymph nodes (CLNs) as a brain-peripheral crosstalk lymphatic pathway in ischemic stroke. In addition, we also summarize the mechanisms of anti-inflammatory drugs in the treatment of ischemic stroke.
PubMed: 38932932
DOI: 10.3389/fnmol.2024.1400808 -
Journal of Veterinary Internal Medicine Jun 2024The information relating to the outcome specifically for juvenile dogs with meningoencephalitis of unknown etiology (MUE) is lacking.
BACKGROUND
The information relating to the outcome specifically for juvenile dogs with meningoencephalitis of unknown etiology (MUE) is lacking.
OBJECTIVES
To describe the clinical presentation, diagnostic findings, treatment, and outcome in a cohort of dogs with MUE <52 weeks old.
ANIMALS
Thirty-four client-owned dogs.
METHODS
Multicenter retrospective case series. Records from 5 referral centers were searched. Data was extracted from the medical records and referring veterinarians were contacted for survival data if this was not available from the record.
RESULTS
The mean age was 31 weeks; the youngest dog was 11 weeks and 3 dogs were <16 weeks old. Altered mentation (71%), ataxia (44%), seizures (29%), and circling (26%) were the most common presenting complaints. Neuroanatomical localization was to the forebrain (38%), multifocal (35%), brainstem (18%), and cerebellum (12%). Corticosteroid monotherapy (n = 15) and corticosteroid plus cytosine arabinoside (n = 15) were used in equal proportions. Outcome data was available for 26 dogs, 8 (31%) were alive at the time of data collection with a follow-up range of 135 to 2944 days. Death or euthanasia was related to MUE in 17/18 dogs that died during the study period. Kaplan-Meier survival analysis demonstrated a median survival time for all-cause death of 84 days.
CONCLUSION
The prognosis for MUE in this subset of dogs was considered poor.
PubMed: 38932495
DOI: 10.1111/jvim.17126 -
Vaccines Jun 2024Glioblastoma (GBM) is the most common and aggressive malignant brain tumor. Standard treatments including surgical resection, radiotherapy, and chemotherapy, have failed... (Review)
Review
Glioblastoma (GBM) is the most common and aggressive malignant brain tumor. Standard treatments including surgical resection, radiotherapy, and chemotherapy, have failed to significantly improve the prognosis of glioblastoma patients. Currently, immunotherapeutic approaches based on vaccines, chimeric antigen-receptor T-cells, checkpoint inhibitors, and oncolytic virotherapy are showing promising results in clinical trials. The combination of different immunotherapeutic approaches is proving satisfactory and promising. In view of the challenges of immunotherapy and the resistance of glioblastomas, the treatment of these tumors requires further efforts. In this review, we explore the obstacles that potentially influence the efficacy of the response to immunotherapy and that should be taken into account in clinical trials. This article provides a comprehensive review of vaccine therapy for glioblastoma. In addition, we identify the main biomarkers, including isocitrate dehydrogenase, epidermal growth factor receptor, and telomerase reverse transcriptase, known as potential immunotherapeutic targets in glioblastoma, as well as the current status of clinical trials. This paper also lists proposed solutions to overcome the obstacles facing immunotherapy in glioblastomas.
PubMed: 38932383
DOI: 10.3390/vaccines12060655