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Journal of Alzheimer's Disease : JAD 2023Perfusion imaging has the potential to identify neurodegenerative disorders in a preclinical stage. However, to correctly interpret perfusion-derived parameters, the...
BACKGROUND
Perfusion imaging has the potential to identify neurodegenerative disorders in a preclinical stage. However, to correctly interpret perfusion-derived parameters, the impact of perfusion modifiers should be evaluated.
OBJECTIVE
In this systematic review, the impact of acute and chronic intake of four acetylcholinesterase inhibitors (AChEIs) on cerebral perfusion in adults was investigated: physostigmine, donepezil, galantamine, and rivastigmine.
RESULTS
Chronic AChEI treatment results in an increase of cerebral perfusion in treatment-responsive patients with Alzheimer's disease, dementia with Lewy bodies, and Parkinson's disease dementia in the frontal, parietal, temporal, and occipital lobes, as well as the cingulate gyrus. These effects appear to be temporary, dose-related, and consistent across populations and different AChEI types. On the contrary, further perfusion decline was reported in patients not receiving AChEIs or not responding to the treatment.
CONCLUSION
AChEIs appear to be a potential perfusion modifier in neurodegenerative patients. More research focused on quantitative perfusion in both patients with and without a cholinergic deficit is needed to draw conclusions on whether AChEI intake should be considered when analyzing perfusion data.
Topics: Humans; Cholinesterase Inhibitors; Acetylcholinesterase; Dementia; Piperidines; Indans; Phenylcarbamates; Parkinson Disease; Rivastigmine; Alzheimer Disease; Galantamine; Cognition; Perfusion; Cerebrovascular Circulation
PubMed: 37182871
DOI: 10.3233/JAD-221125 -
Journal of Clinical Medicine Dec 2022The gap between the demand and supply of donor livers is still a considerable challenge. Since static cold storage is not sufficient in marginal livers, machine... (Review)
Review
BACKGROUND
The gap between the demand and supply of donor livers is still a considerable challenge. Since static cold storage is not sufficient in marginal livers, machine perfusion is being explored as an alternative. The objective of this study was to assess (dual) hypothermic oxygenated machine perfusion (HOPE/D-HOPE) and normothermic machine perfusion (NMP) in contrast to static cold storage (SCS).
METHODS
Three databases were searched to identify studies about machine perfusion. Graft and patient survival and postoperative complications were evaluated using the random effects model.
RESULTS
the incidence of biliary complications was lower in HOPE vs. SCS (OR: 0.59, 95% CI: 0.36-0.98, = 0.04, : 0%). There was no significant difference in biliary complications between NMP and SCS (OR: 0.76, 95% CI: 0.41-1.40, = 0.38, : 55%). Graft and patient survival were significantly better in HOPE than in SCS (HR: 0.40, 95% CI: 0.23-0.71, = 0.002, : 0%) and (pooled HR: 0.43, 95% CI: 0.20-0.93, = 0.03, : 0%). Graft and patient survival were not significantly different between NMP and SCS.
CONCLUSION
HOPE/D-HOPE and NMP are promising alternatives to SCS for donor liver preservation. They may help address the widening gap between the demand for and availability of donor livers by enabling the rescue and transplantation of marginal livers.
PubMed: 36615037
DOI: 10.3390/jcm12010235 -
Movement Disorders : Official Journal... Jul 2022Mutations in the GBA gene cause Gaucher's disease (GD) and constitute the most frequent genetic risk factor for idiopathic Parkinson's disease (iPD). Nonmanifesting... (Review)
Review
BACKGROUND
Mutations in the GBA gene cause Gaucher's disease (GD) and constitute the most frequent genetic risk factor for idiopathic Parkinson's disease (iPD). Nonmanifesting carriers of GBA mutations/variants (GBA-NMC) constitute a potential PD preclinical population, whereas PD patients carrying some GBA mutations/variants (GBA-PD) have a higher risk of a more aggressive disease course. Different neuroimaging techniques are emerging as potential biomarkers in PD and have been used to study GBA-associated parkinsonism.
OBJECTIVE
The aim is to critically review studies applying neuroimaging to GBA-associated parkinsonism.
METHODS
Literature search was performed using PubMed and EMBASE databases (last search February 7, 2022). Studies reporting neuroimaging findings in GBA-PD, GD with and without parkinsonism, and GBA-NMC were included.
RESULTS
Thirty-five studies were included. In longitudinal studies, GBA-PD patients show a more aggressive disease than iPD at both structural magnetic resonance imaging and 123-fluoropropylcarbomethoxyiodophenylnortropane single-photon emission computed tomography. Fluorodeoxyglucose-positron emission tomography and brain perfusion studies reported a greater cortical involvement in GBA-PD compared to iPD. Overall, contrasting evidence is available regarding GBA-NMC for imaging and clinical findings, although subtle differences have been reported compared with healthy controls with no mutations.
CONCLUSIONS
Although results must be interpreted with caution due to limitations of the studies, in line with previous clinical observations, GBA-PD showed a more aggressive disease progression in neuroimaging longitudinal studies compared to iPD. Cognitive impairment, a "clinical signature" of GBA-PD, seems to find its neuroimaging correlate in the greater cortical burden displayed by these patients as compared to iPD. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
Topics: Gaucher Disease; Glucosylceramidase; Humans; Neuroimaging; Parkinson Disease; Parkinsonian Disorders
PubMed: 35521899
DOI: 10.1002/mds.29047 -
International Journal of Environmental... Oct 2022The use of arginine vasopressin (AVP) and terlipressin to treat hypotension in preterm neonates is increasing. Our aim was to review the available evidence on the... (Review)
Review
INTRODUCTION
The use of arginine vasopressin (AVP) and terlipressin to treat hypotension in preterm neonates is increasing. Our aim was to review the available evidence on the efficacy and safety of AVP and terlipressin for use in preterm neonates.
METHODS
MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, Web of Science, and Google Scholar from inception to September 2021 were searched for studies of AVP and terlipressin in the treatment of hypotension of any cause in preterm neonates. Primary outcomes were improvement in end-organ perfusion and mortality. The risk of bias assessment and certainty of the evidence were performed using appropriate tools.
RESULTS
Fifteen studies describing the use of AVP (n = 12) or terlipressin (n = 3) among 148 preterm neonates were included. Certainly, the available evidence for the primary outcome of end-organ perfusion rated as very low. AVP or terlipressin were used to treat 144 and 4 neonates, respectively. Improvement in markers of end-organ perfusion was reported in 143 (99%) neonates treated with AVP and 3 (75%) treated with terlipressin. The mortality rate was 41% (n = 59) and 50% (n = 2) for neonates who received AVP and terlipressin, respectively. Hyponatremia was the most frequently reported adverse event (n = 37, 25%).
CONCLUSION
AVP and terlipressin may improve measured blood pressure values and possibly end-organ perfusion among neonates with refractory hypotension. However, the efficacy-safety balance of these drugs should be assessed on an individual basis and as per the underlying cause. Studies on the optimal dosing, efficacy, and safety of AVP and terlipressin in preterm neonates with variable underlying conditions are critically needed.
Topics: Infant, Newborn; Humans; Terlipressin; Lypressin; Vasoconstrictor Agents; Vasopressins; Arginine Vasopressin; Hypotension
PubMed: 36360641
DOI: 10.3390/ijerph192113760 -
Fluids and Barriers of the CNS Dec 2023The neurovascular unit (NVU) is a complex structure that facilitates nutrient delivery and metabolic waste clearance, forms the blood-brain barrier (BBB), and supports... (Review)
Review
The neurovascular unit (NVU) is a complex structure that facilitates nutrient delivery and metabolic waste clearance, forms the blood-brain barrier (BBB), and supports fluid homeostasis in the brain. The integrity of NVU subcomponents can be measured in vivo using magnetic resonance imaging (MRI), including quantification of enlarged perivascular spaces (ePVS), BBB permeability, cerebral perfusion and extracellular free water. The breakdown of NVU subparts is individually associated with aging, pathology, and cognition. However, how these subcomponents interact as a system, and how interdependencies are impacted by pathology remains unclear. This systematic scoping review identified 26 studies that investigated the inter-relationships between multiple subcomponents of the NVU in nonclinical and neurodegenerative populations using MRI. A further 112 studies investigated associations between the NVU and white matter hyperintensities (WMH). We identify two putative clusters of NVU interdependencies: a 'vascular' cluster comprising BBB permeability, perfusion and basal ganglia ePVS; and a 'fluid' cluster comprising ePVS, free water and WMH. Emerging evidence suggests that subcomponent coupling within these clusters may be differentially related to aging, neurovascular injury or neurodegenerative pathology.
Topics: Magnetic Resonance Imaging; Brain; Blood-Brain Barrier; Water
PubMed: 38129925
DOI: 10.1186/s12987-023-00499-0 -
Journal of Clinical Medicine Jun 2023The high demand for organs in kidney transplantation and the expansion of the donor pool have led to the widespread implementation of machine perfusion technologies. In... (Review)
Review
The high demand for organs in kidney transplantation and the expansion of the donor pool have led to the widespread implementation of machine perfusion technologies. In this study, we aim to provide an up-to-date systematic review of the developments in this expanding field over the past 10 years, with the aim of answering the question: "which perfusion technique is the most promising technique in kidney transplantation?" A systematic review of the literature related to machine perfusion in kidney transplantation was performed. The primary outcome measure was delayed graft function (DGF), and secondary outcomes included rates of rejection, graft survival, and patient survival rates after 1 year. Based on the available data, a meta-analysis was performed. The results were compared with data from static cold storage, which is still the standard of care in many centers worldwide. A total of 56 studies conducted in humans were included, and 43 studies reported outcomes of hypothermic machine perfusion (HMP), with a DGF rate of 26.4%. A meta-analysis of 16 studies showed significantly lower DGF rates in the HMP group compared to those of static cold storage (SCS). Five studies reported outcomes of hypothermic machine perfusion + O, with an overall DGF rate of 29.7%. Two studies explored normothermic machine perfusion (NMP). These were pilot studies, designed to assess the feasibility of this perfusion approach in the clinical setting. Six studies reported outcomes of normothermic regional perfusion (NRP). The overall incidence of DGF was 71.5%, as it was primarily used in uncontrolled DCD (Maastricht category I-II). Three studies comparing NRP to in situ cold perfusion showed a significantly lower rate of DGF with NRP. The systematic review and meta-analysis provide evidence that dynamic preservation strategies can improve outcomes following kidney transplantation. More recent approaches such as normothermic machine perfusion and hypothermic machine perfusion + O do show promising results but need further results from the clinical setting. This study shows that the implementation of perfusion strategies could play an important role in safely expanding the donor pool.
PubMed: 37373568
DOI: 10.3390/jcm12123871 -
Abdominal Radiology (New York) Sep 2022Pancreatic ductal adenocarcinoma (PDAC) is the third leading cause of cancer-related death with a 5-year survival rate of 10%. Quantitative CT perfusion (CTP) can... (Review)
Review
Pancreatic ductal adenocarcinoma (PDAC) is the third leading cause of cancer-related death with a 5-year survival rate of 10%. Quantitative CT perfusion (CTP) can provide additional diagnostic information compared to the limited accuracy of the current standard, contrast-enhanced CT (CECT). This systematic review evaluates CTP for diagnosis, grading, and treatment assessment of PDAC. The secondary goal is to provide an overview of scan protocols and perfusion models used for CTP in PDAC. The search strategy combined synonyms for 'CTP' and 'PDAC.' Pubmed, Embase, and Web of Science were systematically searched from January 2000 to December 2020 for studies using CTP to evaluate PDAC. The risk of bias was assessed using QUADAS-2. 607 abstracts were screened, of which 29 were selected for full-text eligibility. 21 studies were included in the final analysis with a total of 760 patients. All studies comparing PDAC with non-tumorous parenchyma found significant CTP-based differences in blood flow (BF) and blood volume (BV). Two studies found significant differences between pathological grades. Two other studies showed that BF could predict neoadjuvant treatment response. A wide variety in kinetic models and acquisition protocol was found among included studies. Quantitative CTP shows a potential benefit in PDAC diagnosis and can serve as a tool for pathological grading and treatment assessment; however, clinical evidence is still limited. To improve clinical use, standardized acquisition and reconstruction parameters are necessary for interchangeability of the perfusion parameters.
Topics: Carcinoma, Pancreatic Ductal; Humans; Pancreatic Neoplasms; Perfusion Imaging; Tomography, X-Ray Computed
PubMed: 34223961
DOI: 10.1007/s00261-021-03190-w -
JTCVS Open Dec 2021A meta-analysis of randomized controlled trials was performed to compare the effects of miniaturized extracorporeal circulation (MECC) and conventional extracorporeal...
OBJECTIVE
A meta-analysis of randomized controlled trials was performed to compare the effects of miniaturized extracorporeal circulation (MECC) and conventional extracorporeal circulation (CECC) on morbidity and mortality rates after cardiac surgery.
METHODS
A comprehensive literature search was conducted using Ovid, PubMed, Medline, EMBASE, and the Cochrane databases. Randomized controlled trials from the year 2000 with n > 40 patients were considered. Key search terms included variations of "mini," "cardiopulmonary," "bypass," "extracorporeal," "perfusion," and "circuit." Studies were assessed for bias using the Cochrane Risk of Bias tool. The primary outcomes were postoperative mortality and stroke. Secondary outcomes included arrhythmia, myocardial infarction, renal failure, blood loss, and a composite outcome comprised of mortality, stroke, myocardial infarction and renal failure. Duration of intensive care unit, and hospital stay was also recorded.
RESULTS
The 42 studies eligible for this study included a total of 2154 patients who underwent CECC and 2196 patients who underwent MECC. There were no significant differences in any preoperative or demographic characteristics. Compared with CECC, MECC did not reduce the incidence of mortality, stroke, myocardial infarction, and renal failure but did significantly decrease the composite of these outcomes (odds ratio, 0.64; 95% confidence interval [CI], 0.50-0.81; = .0002). MECC was also associated with reductions in arrhythmia (odds ratio, 0.67; 95% CI, 0.54-0.83; = .0003), blood loss (mean difference [MD], -96.37 mL; 95% CI, -152.70 to -40.05 mL; = .0008), hospital stay (MD, -0.70 days; 95% CI, -1.21 to -0.20 days; = .006), and intensive care unit stay (MD, -2.27 hours; 95% CI, -3.03 to -1.50 hours; < .001).
CONCLUSIONS
MECC demonstrates clinical benefits compared with CECC. Further studies are required to perform a cost-utility analysis and to assess the long-term outcomes of MECC. These should use standardized definitions of endpoints such as mortality and renal failure to reduce inconsistency in outcome reporting.
PubMed: 36004169
DOI: 10.1016/j.xjon.2021.09.037 -
Journal of Stroke May 2023Intracranial arterial stenosis (ICAS)-related stroke occurs due to three primary mechanisms with distinct infarct patterns: (1) borderzone infarcts (BZI) due to impaired... (Review)
Review
BACKGROUND AND PURPOSE
Intracranial arterial stenosis (ICAS)-related stroke occurs due to three primary mechanisms with distinct infarct patterns: (1) borderzone infarcts (BZI) due to impaired distal perfusion, (2) territorial infarcts due to distal plaque/thrombus embolization, and (3) plaque progression occluding perforators. The objective of the systematic review is to determine whether BZI secondary to ICAS is associated with a higher risk of recurrent stroke or neurological deterioration.
METHODS
As part of this registered systematic review (CRD42021265230), a comprehensive search was performed to identify relevant papers and conference abstracts (with ≥20 patients) reporting initial infarct patterns and recurrence rates in patients with symptomatic ICAS. Subgroup analyses were performed for studies including any BZI versus isolated BZI and those excluding posterior circulation stroke. The study outcome included neurological deterioration or recurrent stroke during follow-up. For all outcome events, corresponding risk ratios (RRs) and 95% confidence intervals (95% CI) were calculated.
RESULTS
A literature search yielded 4,478 records with 32 selected during the title/abstract triage for full text; 11 met inclusion criteria and 8 studies were included in the analysis (n=1,219 patients; 341 with BZI). The meta-analysis demonstrated that the RR of outcome in the BZI group compared to the no BZI group was 2.10 (95% CI 1.52-2.90). Limiting the analysis to studies including any BZI, the RR was 2.10 (95% CI 1.38-3.18). For isolated BZI, RR was 2.59 (95% CI 1.24-5.41). RR was 2.96 (95% CI 1.71-5.12) for studies only including anterior circulation stroke patients.
CONCLUSION
This systematic review and meta-analysis suggests that the presence of BZI secondary to ICAS may be an imaging biomarker that predicts neurological deterioration and/or stroke recurrence.
PubMed: 37282372
DOI: 10.5853/jos.2023.00185 -
Journal of Clinical Medicine Aug 2019To match the current organ demand with organ availability from the donor pool, there has been a shift towards acceptance of extended criteria donors (ECD), often... (Review)
Review
INTRODUCTION
To match the current organ demand with organ availability from the donor pool, there has been a shift towards acceptance of extended criteria donors (ECD), often associated with longer ischemic times. Novel dynamic preservation techniques as hypothermic or normothermic machine perfusion (MP) are increasingly adopted, particularly for organs from ECDs. In this study, we compared the viability and incidence of reperfusion injury in kidneys and livers preserved with MP versus Static Cold Storage (SCS).
METHODS
Systematic review and meta-analysis with a search performed between February and March 2019. MEDLINE, EMBASE and Transplant Library were searched via OvidSP. The Cochrane Library and The Cochrane Central Register of Controlled Trials (CENTRAL) were also searched. English language filter was applied.
RESULTS
the systematic search generated 10,585 studies, finally leading to a total of 30 papers for meta-analysis of kidneys and livers. Hypothermic MP (HMP) statistically significantly lowered the incidence of primary nonfunction (PMN, = 0.003) and delayed graft function (DGF, < 0.00001) in kidneys compared to SCS, but not its duration. No difference was also noted for serum creatinine or eGFR post-transplantation, but overall kidneys preserved with HMP had a significantly longer one-year graft survival (OR: 1.61 95% CI: 1.02 to 2.53, = 0.04). Differently from kidneys where the graft survival was affected, there was no significant difference in primary non function (PNF) for livers stored using SCS for those preserved by HMP and NMP. Machine perfusion demonstrated superior outcomes in early allograft dysfunction and post transplantation AST levels compared to SCS, but however, only HMP was able to significantly decrease serum bilirubin and biliary stricture incidence compared to SCS.
CONCLUSIONS
MP improves DGF and one-year graft survival in kidney transplantation; it appears to mitigate early allograft dysfunction in livers, but more studies are needed to prove its potential superiority in relation to PNF in livers.
PubMed: 31443179
DOI: 10.3390/jcm8081221