-
FASEB Journal : Official Publication of... Apr 2024Exosomes, which are small membrane-encapsulated particles derived from all cell types, are emerging as important mechanisms for intercellular communication. In addition,...
Exosomes, which are small membrane-encapsulated particles derived from all cell types, are emerging as important mechanisms for intercellular communication. In addition, exosomes are currently envisioned as potential carriers for the delivery of drugs to target tissues. The natural population of exosomes is very variable due to the limited amount of cargo components present in these small vesicles. Consequently, common components of exosomes may play a role in their function. We have proposed that membrane phospholipids could be a common denominator in the effect of exosomes on cellular functions. In this regard, we have previously shown that liposomes made of phosphatidylcholine (PC) or phosphatidylserine (PS) induced a robust alteration of macrophage (Mϕ) gene expression. We herewith report that these two phospholipids modulate gene expression in Mϕs by different mechanisms. PS alters cellular responses by the interaction with surface receptors, particularly CD36. In contrast, PC is captured by a receptor-independent process and likely triggers an activity within endocytic vesicles. Despite this difference in the capture mechanisms, both lipids mounted similar gene expression responses. This investigation suggests that multiple mechanisms mediated by membrane phospholipids could be participating in the alteration of cellular functions by exosomes.
Topics: Macrophages; Animals; Mice; Phosphatidylserines; Exosomes; Phosphatidylcholines; Inflammation; Phospholipids; Mice, Inbred C57BL; CD36 Antigens; Liposomes
PubMed: 38661031
DOI: 10.1096/fj.202302471R -
Netherlands Heart Journal : Monthly... Jun 2024Idiopathic ventricular fibrillation (iVF) is a rare cause of sudden cardiac arrest and, by definition, a diagnosis of exclusion. Due to the rarity of the disease,...
BACKGROUND
Idiopathic ventricular fibrillation (iVF) is a rare cause of sudden cardiac arrest and, by definition, a diagnosis of exclusion. Due to the rarity of the disease, previous and current studies are limited by their retrospective design and small patient numbers. Even though the incidence of iVF has declined owing to the identification of new disease entities, an important subgroup of patients remains.
AIM
To expand the existing Dutch iVF Registry into a large nationwide cohort of patients initially diagnosed with iVF, to reveal the underlying cause of iVF in these patients, and to improve arrhythmia management.
METHODS
The Dutch iVF Registry includes sudden cardiac arrest survivors with an initial diagnosis of iVF. Clinical data and outcomes are collected. Outcomes include subsequent detection of a diagnosis other than 'idiopathic', arrhythmia recurrence and death. Non-invasive electrocardiographic imaging is used to investigate electropathological substrates and triggers of VF.
RESULTS
To date, 432 patients have been included in the registry (median age at event 40 years (interquartile range 28-52)), 61% male. During a median follow-up of 6 (2-12) years, 38 patients (9%) received a diagnosis other than 'idiopathic'. Eleven iVF patients were characterised with electrocardiographic imaging.
CONCLUSION
The Dutch iVF Registry is currently the largest of its kind worldwide. In this heterogeneous population of index patients, we aim to identify common functional denominators associated with iVF. With the implementation of non-invasive electrocardiographic imaging and other diagnostic modalities (e.g. echocardiographic deformation, cardiac magnetic resonance), we advance the possibilities to reveal pro-fibrillatory substrates.
PubMed: 38653923
DOI: 10.1007/s12471-024-01870-y -
Human Molecular Genetics Apr 2024Intellectual disability (ID) and autism spectrum disorder (ASD) are genetically heterogeneous with hundreds of identified risk genes, most affecting only a few patients....
Intellectual disability (ID) and autism spectrum disorder (ASD) are genetically heterogeneous with hundreds of identified risk genes, most affecting only a few patients. Novel missense variants in these genes are being discovered as clinical exome sequencing is now routinely integrated into diagnosis, yet most of them are annotated as variants of uncertain significance (VUS). VUSs are a major roadblock in using patient genetics to inform clinical action. We developed a framework to characterize VUSs in Coiled-coil and C2 domain containing 1A (CC2D1A), a gene causing autosomal recessive ID with comorbid ASD in 40% of cases. We analyzed seven VUSs (p.Pro319Leu, p.Ser327Leu, p.Gly441Val, p.Val449Met, p.Thr580Ile, p.Arg886His and p.Glu910Lys) from four cases of individuals with ID and ASD. Variants were cloned and overexpressed in HEK293 individually and in their respective heterozygous combination. CC2D1A is a signaling scaffold that positively regulates PKA-CREB signaling by repressing phosphodiesterase 4D (PDE4D) to prevent cAMP degradation. After testing multiple parameters including direct interaction between PDE4D and CC2D1A, cAMP levels and CREB activation, we found that the most sensitive readout was CREB transcriptional activity using a luciferase assay. Compared to WT CC2D1A, five VUSs (p.Pro319Leu, p.Gly441Val, p.Val449Met, p.Thr580Ile, and p.Arg886His) led to significantly blunted response to forskolin induced CREB activation. This luciferase assay approach can be scaled up to annotate ~150 CC2D1A VUSs that are currently listed in ClinVar. Since CREB activation is a common denominator for multiple ASD/ID genes, our paradigm can also be adapted for their VUSs.
PubMed: 38652285
DOI: 10.1093/hmg/ddae070 -
Supportive Care in Cancer : Official... Apr 2024In treating cancer, different chemotherapy regimens cause chemotherapy-induced peripheral neuropathy (CIPN). Despite recent international guidelines, a gold standard for...
A qualitative evaluation of the oncologists', neurologists', and pain specialists' views on the management and care of chemotherapy-induced peripheral neuropathy in The Netherlands.
PURPOSE
In treating cancer, different chemotherapy regimens cause chemotherapy-induced peripheral neuropathy (CIPN). Despite recent international guidelines, a gold standard for diagnosis, treatment, and care is lacking. To identify the current clinical practice and the physicians' point of view and ideas for improvement, we evaluated CIPN care by interviewing different specialists involved.
METHODS
We performed semi-structured, audio-recorded, transcribed, and coded interviews with a purposive sample of oncologists, pain specialists, and neurologists involved in CIPN patients' care. Data is analyzed by a constant comparative method for content analysis, using ATLAS.ti software. Codes, categories, and themes are extracted, generating common denominators and conclusions.
RESULTS
With oncologists, pain specialists, and neurologists, nine, nine, and eight interviews were taken respectively (including three, two, and two interviews after thematic saturation occurred). While useful preventive measures and predictors are lacking, patient education (e.g., on symptoms and timely reporting) is deemed pivotal, as is low-threshold screening (e.g., anamnesis and questionnaires). Diagnosis focusses on a temporal relationship to chemotherapy, with adjuvant testing (e.g., EMG) used in severe or atypical cases. Symptomatic antineuropathic and topical medication are often prescribed, but personalized and multidimensional care based on individual symptoms and preferences is highly valued. The limited efficacy of existing treatments, and the lack of standardized protocols, interdisciplinary coordination, and awareness among healthcare providers pose significant challenges.
CONCLUSION
Besides the obvious need for better therapeutic options, and multidisciplinary exploration of patients' perspectives, a structured and collaborative approach towards diagnosis, treatment, referral, and follow-up, nurtured by improving knowledge and use of existing CIPN guidelines, could enhance care.
Topics: Humans; Peripheral Nervous System Diseases; Netherlands; Oncologists; Antineoplastic Agents; Neurologists; Attitude of Health Personnel; Qualitative Research; Male; Female; Interviews as Topic; Neoplasms; Middle Aged; Pain Management
PubMed: 38647694
DOI: 10.1007/s00520-024-08493-4 -
Effect of changing the radiation dose range on the in vitro cytogenetic dose response to gamma-rays.International Journal of Radiation... 2024To examine the distortion of the linear quadratic (LQ) model of in vitro cytogenetic dose response over an extended range of γ-ray doses by analyzing the available...
PURPOSE
To examine the distortion of the linear quadratic (LQ) model of in vitro cytogenetic dose response over an extended range of γ-ray doses by analyzing the available literature data, and to establish the dose ranges, in which the LQ dose response curve (DRC) can be most accurately fitted for biological dosimetry.
MATERIALS AND METHODS
Data on yields of dicentrics (Dic) or dicentrics plus centric rings (Dic + CR) induced in vitro in human lymphocytes by acute γ-rays were extracted from 108 open sources. The overall dose response dataset in the dose range up to 50 Gy was fitted to a fractional-rational (FR) model, which included a 'basic' LQ function in the numerator, and a reduction factor dependent on the square of the dose in the denominator. Cytogenetic dose response data obtained at Grigoriev Institute for Medical Radiology, Kharkiv, Ukraine (GIMRO) in the range 0.1 - 20.3 Gy acute γ-rays were fitted to the LQ model with the progressive changing minimum or maximum radiation dose.
RESULTS
The overall dose response, as expected, followed the LQ function in the dose range ≤5 Gy, but in the extended dose range appeared to be S-shaped, with intensive saturation and a plateau at doses ≥22 Gy. Coefficients of the 'basic' LQ equation in FR model were very close to many published DRCs; calculated asymptote was 17. Fitting of the GIMRO dataset to the LQ model with the shift of the dose range showed the increase in linear coefficient with the increment of either minimum or maximum radiation dose, while the decline of the quadratic coefficient was regulated mostly by the increase of the highest dose. The best goodness of fit, assessed by lower χ values, occurred for dose ranges 0.1 - 1.0 Gy; 0.5 - 5.9 Gy; 1.0 - 7.8 Gy; 2.0 - 9.6 Gy, 3.9 - 16.4 Gy and 5.9 - 20.3 Gy. The 'see-saw' effect in changes of LQ coefficients was confirmed by re-fitting datasets published by other laboratories.
CONCLUSIONS
The classical LQ model with fixed coefficients appears to have limited applicability for cytogenetic dosimetry at radiation doses >5 Gy due to the saturation of the dose response. Different response of the LQ coefficients to the changes of the dose range must be considered during the DRC construction. Proper selection of minimum and maximum dose in calibration experiments makes it possible to improve the goodness of fit of the LQ DRC.
Topics: Gamma Rays; Humans; Dose-Response Relationship, Radiation; Chromosome Aberrations; Cytogenetic Analysis; Lymphocytes; Radiation Dosage; Radiometry
PubMed: 38647504
DOI: 10.1080/09553002.2024.2338511 -
International Journal of Nursing Studies Jul 2024Numerous interventions for pressure injury prevention have been developed, including care bundles. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Numerous interventions for pressure injury prevention have been developed, including care bundles.
OBJECTIVE
To systematically review the effectiveness of pressure injury prevention care bundles on pressure injury prevalence, incidence, and hospital-acquired pressure injury rate in hospitalised patients.
DATA SOURCES
The Medical Literature Analysis and Retrieval System Online (via PubMed), the Cumulative Index to Nursing and Allied Health Literature, EMBASE, Scopus, the Cochrane Library and two registries were searched (from 2009 to September 2023).
STUDY ELIGIBILITY CRITERIA
Randomised controlled trials and non-randomised studies with a comparison group published in English after 2008 were included. Studies reporting on the frequency of pressure injuries where the number of patients was not the numerator or denominator, or where the denominator was not reported, and single subgroups of hospitalised patients were excluded. Educational programmes targeting healthcare professionals and bundles targeting specific types of pressure injuries were excluded.
PARTICIPANTS AND INTERVENTIONS
Bundles with ≥3 components directed towards patients and implemented in ≥2 hospital services were included.
STUDY APPRAISAL AND SYNTHESIS METHODS
Screening, data extraction and risk of bias assessments were undertaken independently by two researchers. Random effects meta-analyses were conducted. The certainty of the body of evidence was assessed using Grading of Recommendations, Assessment, Development and Evaluation.
RESULTS
Nine studies (seven non-randomised with historical controls; two randomised) conducted in eight countries were included. There were four to eight bundle components; most were core, and only a few were discretionary. Various strategies were used prior to (six studies), during (five studies) and after (two studies) implementation to embed the bundles. The pooled risk ratio for pressure injury prevalence (five non-randomised studies) was 0.55 (95 % confidence intervals 0.29-1.03), and for hospital-acquired pressure injury rate (five non-randomised studies) it was 0.31 (95 % confidence intervals 0.12-0.83). All non-randomised studies were at high risk of bias, with very low certainty of evidence. In the two randomised studies, the care bundles had non-significant effects on hospital-acquired pressure injury incidence density, but data could not be pooled.
CONCLUSIONS AND IMPLICATIONS OF KEY FINDINGS
Whilst some studies showed decreases in pressure injuries, this evidence was very low certainty. The potential benefits of adding emerging evidence-based components to bundles should be considered. Future effectiveness studies should include contemporaneous controls and the development of a comprehensive, theory and evidence-informed implementation plan.
SYSTEMATIC REVIEW REGISTRATION NUMBER
PROSPERO CRD42023423058.
TWEETABLE ABSTRACT
Pressure injury prevention care bundles decrease hospital-acquired pressure injuries, but the certainty of this evidence is very low.
Topics: Pressure Ulcer; Humans; Patient Care Bundles; Hospitalization
PubMed: 38642429
DOI: 10.1016/j.ijnurstu.2024.104768 -
Trends in Immunology May 2024Mammalian brain border-associated macrophages (BAMs) are strategically positioned to support vital properties and processes: for example, the composition of the brain's...
Mammalian brain border-associated macrophages (BAMs) are strategically positioned to support vital properties and processes: for example, the composition of the brain's perivascular extracellular matrix and cerebrospinal fluid flow via the glymphatic pathway. BAMs also effectively restrict the spread of infectious microbes into the brain. However, while fighting infections, BAMs sustain long-term transcriptomic changes and can be replaced by inflammatory monocytes, potentially leading to a gradual loss of their beneficial homeostatic functions. We hypothesize that by expediting the deterioration of BAMs, multiple infection episodes might be associated with accelerated brain aging and the putative development of neurodegenerative diseases. Our viewpoint is supported by recent studies suggesting that rejuvenating aged BAMs, and counterbalancing their detrimental inflammatory signatures during infections, might hold promise in treating aging-related neurological disorders, including Alzheimer's disease (AD).
Topics: Animals; Humans; Aging; Alzheimer Disease; Brain; Infections; Macrophages
PubMed: 38632001
DOI: 10.1016/j.it.2024.03.007 -
European Heart Journal. Quality of Care... Apr 2024Thirty-day readmission rate after heart failure (HF) hospitalization is widely used to evaluate healthcare quality. Methodology may substantially influence estimated...
Impact of the method of calculating 30-day readmission rate after hospitalization for heart failure. Data from the VancOuver CoastAL Acute Heart Failure (VOCAL-AHF) registry.
BACKGROUND
Thirty-day readmission rate after heart failure (HF) hospitalization is widely used to evaluate healthcare quality. Methodology may substantially influence estimated rates. We assessed the impact of different definitions on HF and all-cause readmission rates.
METHODS
Readmission rates were examined in 1,835 patients discharged following HF hospitalization using 64 unique definitions derived from five methodological factors: (1) ICD-10 codes (broad vs narrow), (2) index admission selection (single admission only first-in-year vs. random sample; or multiple admissions in year with vs. without 30-day blanking period), (3) variable denominator (number alive at discharge vs. number alive at 30-days), (4) follow-up period start (discharge date vs day following discharge), and (5) annual reference-period (calendar vs fiscal). The impact of different factors was assessed using linear-regression.
RESULTS
The calculated 30-day readmission rate for HF varied more than 2-fold depending solely on the methodological approach (6.5% to 15.0%). All-cause admission rates exhibited similar variation (18.8% to 29.9%). The highest rates included all consecutive index admissions (HF 11.1-15.0%, all-cause 24.0-29.9%), and lowest only one index admission per patient per year (HF 6.5-11.3%, all-cause 18.8-22.7%). When including multiple index admissions and compared to blanking the 30-days post-discharge, not blanking was associated with 2.3% higher readmission rates. Selecting a single admission per year with a first-in-year approach lowered readmission rates by 1.5%, while random-sampling admissions lowered estimates further by 5.2% (p<0.001).
CONCLUSION
Calculated 30-day readmission rates varied more than 2-fold by altering methods. Transparent and consistent methods are needed to ensure reproducible and comparable reporting.
PubMed: 38609346
DOI: 10.1093/ehjqcco/qcae026 -
Annals of Cardiac Anaesthesia Apr 2024The potential benefits of epidural anesthesia on mortality, atrial fibrillation, and pulmonary complications must be weighed against the risk of epidural hematoma...
The potential benefits of epidural anesthesia on mortality, atrial fibrillation, and pulmonary complications must be weighed against the risk of epidural hematoma associated with intraoperative heparinization. This study aims to provide an updated assessment of the clinical risks of epidural anesthesia in cardiac surgery, focusing on the occurrence of epidural hematomas and subsequent paralysis. A systematic search of Embase, Medline, Ovid Central, Web of Science, and PubMed was conducted to identify relevant publications between 1966 and 2022. Two independent reviewers assessed the eligibility of the retrieved manuscripts. Studies reporting adult patients undergoing cardiac surgery with epidural catheterization were included. The incidence of hematomas was calculated by dividing the number of hematomas by the total number of patients in the included studies. Risk calculations utilized various denominators based on the rigor of trial designs, and the risks of hematoma and paralysis were compared to other commonly encountered risks. The analysis included a total of 33,089 patients who underwent cardiac surgery with epidural catheterization. No epidural hematomas were reported across all published RCTs, prospective, and retrospective trials. Four case reports associated epidural hematoma with epidural catheterization and perioperative heparinization. The risks of epidural hematoma and subsequent paralysis were estimated at 1:7643 (95% CI 1:3860 to 380,916) and 1:10,190 (95% CI 1:4781 to 0:1), respectively. The risk of hematoma is similar to the non-obstetric population (1:5405; 95% CI 1:4784 to 6134). The risk of hematoma in cardiac surgery patients receiving epidural anesthesia is therefore similar to that observed in some other surgical non-obstetric populations commonly exposed to epidural catheterization.
Topics: Adult; Humans; Prospective Studies; Retrospective Studies; Cardiac Surgical Procedures; Hematoma; Risk Assessment; Paralysis
PubMed: 38607874
DOI: 10.4103/aca.aca_160_23 -
Journal de Mycologie Medicale Jun 2024With increasing concern about the negative health impact of fungal disease, there is a need to survey what is and is not known about the epidemiology of these infections... (Review)
Review
With increasing concern about the negative health impact of fungal disease, there is a need to survey what is and is not known about the epidemiology of these infections in Tunisia. We have estimated the incidence and prevalence of the most serious fungal diseases in Tunisia for the first time. Using published literature from Tunisia, or if absent other countries, we have estimated the burden of life-threatening fungal infections and those causing significant morbidity, using deterministic modeling, based on populations at greatest risk. An estimated 250,494 (2.12% of the Tunisian population) are affected by a serious fungal disease annually. Invasive and chronic pulmonary aspergillosis are relatively common with 708 and 2090 patients affected, partly linked to the prevalence of chronic obstructive pulmonary disease (COPD). Fungal asthma (allergic bronchopulmonary aspergillosis and severe asthma with fungal sensitization) have an estimated prevalence of 38,264 (5.8% of the adult asthma population). Fungal keratitis probably affects 1,761 eyes annually, often leading to uniocular blindness. Candidaemia and Candida peritonitis probably affect at least 680 people annually, with a high mortality. Recurrent vulvovaginal candidiasis probably affects over 200,000 women. While fungal diseases are regularly diagnosed in Tunisia, epidemiological studies with denominators are uncommon. Some fungal diseases are poorly addressed with the current diagnostic portfolio, and surveillance is lacking. Studies on these diseases and the implementation of a national program of surveillance are required.
Topics: Humans; Tunisia; Prevalence; Incidence; Female; Mycoses; Male; Adult; Asthma; Middle Aged; Pulmonary Disease, Chronic Obstructive; Adolescent; Aged; Candidiasis, Vulvovaginal; Young Adult; Child; Keratitis; Aspergillosis, Allergic Bronchopulmonary; Candidemia; Pulmonary Aspergillosis; Child, Preschool
PubMed: 38604083
DOI: 10.1016/j.mycmed.2024.101479