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Langenbeck's Archives of Surgery Feb 2021Liver transplantation is the only curative treatment option for end-stage liver disease; however, its use remains limited due to a shortage of suitable organs. In recent...
BACKGROUND
Liver transplantation is the only curative treatment option for end-stage liver disease; however, its use remains limited due to a shortage of suitable organs. In recent years, ex vivo liver machine perfusion has been introduced to liver transplantation, as a means to expand the donor organ pool.
PURPOSE
To present a systematic review of prospective clinical studies on ex vivo liver machine perfusion, in order to assess current applications and highlight future directions.
METHODS
A systematic literature search of both PubMed and ISI web of science databases as well as the ClinicalTrials.gov registry was performed.
RESULTS
Twenty-one articles on prospective clinical trials on ex vivo liver machine perfusion were identified. Out of these, eight reported on hypothermic, eleven on normothermic, and two on sequential perfusion. These trials have demonstrated the safety and feasibility of ex vivo liver machine perfusion in both standard and expanded criteria donors. Currently, there are twelve studies enrolled in the clinicaltrials.gov registry, and these focus on use of ex vivo perfusion in extended criteria donors and declined organs.
CONCLUSION
Ex vivo liver machine perfusion seems to be a suitable strategy to expand the donor pool for liver transplantation and holds promise as a platform for reconditioning diseased organs.
Topics: Humans; Liver; Liver Transplantation; Organ Preservation; Perfusion; Prospective Studies; Tissue Donors
PubMed: 33216216
DOI: 10.1007/s00423-020-02014-7 -
Journal of Vascular Surgery Mar 2022Spinal cord ischemia (SCI) is one of the most devastating complications after descending thoracic aortic (DTA) and thoracoabdominal aortic (TAA) repairs. Patients who...
OBJECTIVE
Spinal cord ischemia (SCI) is one of the most devastating complications after descending thoracic aortic (DTA) and thoracoabdominal aortic (TAA) repairs. Patients who develop SCI have a poor prognosis, with mortality rates reaching 75% within the first year after surgery. Many factors have been shown to increase the risk of this complication, including the extent of TAA repair, length of aortic and collateral network coverage, embolization, and reduced spinal cord perfusion pressure. As a result, a variety of treatment strategies have been developed. We aimed to provide an up-to-date review of SCI rates with associated treatment algorithms from open and endovascular DTA and TAA repair.
METHODS
Using PRISMA (preferred reporting items for systematic reviews and meta-analyses) guidelines, a literature review with the MeSH (medical subject headings) terms "spinal cord ischemia," "spinal cord ischemia prevention and mitigation strategies," "spinal cord ischemia rates," and "spinal cord infarction" was performed in the Cochrane and PubMed databases to find all peer-reviewed studies of DTA and TAA repair with SCI complications reported. The search was limited to 2012 to 2021 and English-language reports. MeSH subheadings, including diagnosis, complications, physiopathology, surgery, mortality, and therapy, were used to further restrict the included studies. Studies were excluded if they were not of humans, had not pertained to SCI after DTA or TAA operative repair, and if the study had primarily discussed neuromonitoring techniques. Additionally, studies with <40 patients or limited information regarding SCI protection strategies were excluded. Each study was individually reviewed by two of us (S.L. and A.D.) to assess the type and extent of aortic pathology, operative technique, SCI protection or mitigation strategies, rates of overall and permanent SCI symptoms, associations with SCI on multivariate analysis, and mortality.
RESULTS
Of the 450 studies returned by the MeSH search strategy, 41 met the inclusion criteria and were included in the final analysis. For the endovascular DTA repair patients, the overall SCI rates ranged from 0% to 10.6%, with permanent SCI symptoms ranging from 0% to 5.1%. The rate of overall SCI after endovascular and open TAA repair was 0% to 35%. The permanent SCI symptom rate was reported by only one study of open repair at 1.1%. The permanent SCI symptom rate after endovascular TAA repair was 2% to 20.5%.
CONCLUSIONS
The present review has provided an up-to-date review of the current rates of SCI and the prevention and mitigation strategies used during DTA and TAA repair. We found that a multimodal approach, including a bundled institutional protocol, staging of multiple repairs, preservation of the collateral blood flow network, augmented spinal cord perfusion, selective cerebrospinal fluid drainage, and distal aortic perfusion during open TAA repairs, appears to be important in reducing the risk of SCI.
Topics: Algorithms; Aorta, Thoracic; Aortic Diseases; Blood Vessel Prosthesis Implantation; Decision Support Techniques; Endovascular Procedures; Humans; Risk Assessment; Risk Factors; Spinal Cord Ischemia; Time Factors; Treatment Outcome
PubMed: 34740806
DOI: 10.1016/j.jvs.2021.10.039 -
Acta Neuropathologica Communications Sep 2019Perfusing fixatives through the cerebrovascular system is the gold standard approach in animals to prepare brain tissue for spatial biomolecular profiling, circuit... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Perfusing fixatives through the cerebrovascular system is the gold standard approach in animals to prepare brain tissue for spatial biomolecular profiling, circuit tracing, and ultrastructural studies such as connectomics. Translating these discoveries to humans requires examination of postmortem autopsy brain tissue. Yet banked brain tissue is routinely prepared using immersion fixation, which is a significant barrier to optimal preservation of tissue architecture. The challenges involved in adopting perfusion fixation in brain banks and the extent to which it improves histology quality are not well defined.
METHODOLOGY
We searched four databases to identify studies that have performed perfusion fixation in human brain tissue and screened the references of the eligible studies to identify further studies. From the included studies, we extracted data about the methods that they used, as well as any data comparing perfusion fixation to immersion fixation. The protocol was preregistered at the Open Science Framework: https://osf.io/cv3ys/ .
RESULTS
We screened 4489 abstracts, 214 full-text publications, and identified 35 studies that met our inclusion criteria, which collectively reported on the perfusion fixation of 558 human brains. We identified a wide variety of approaches to perfusion fixation, including perfusion fixation of the brain in situ and ex situ, perfusion fixation through different sets of blood vessels, and perfusion fixation with different washout solutions, fixatives, perfusion pressures, and postfixation tissue processing methods. Through a qualitative synthesis of data comparing the outcomes of perfusion and immersion fixation, we found moderate confidence evidence showing that perfusion fixation results in equal or greater subjective histology quality compared to immersion fixation of relatively large volumes of brain tissue, in an equal or shorter amount of time.
CONCLUSIONS
This manuscript serves as a resource for investigators interested in building upon the methods and results of previous research in designing their own perfusion fixation studies in human brains or other large animal brains. We also suggest several future research directions, such as comparing the in situ and ex situ approaches to perfusion fixation, studying the efficacy of different washout solutions, and elucidating the types of brain donors in which perfusion fixation is likely to result in higher fixation quality than immersion fixation.
Topics: Brain; Humans; Perfusion; Tissue Banks; Tissue Fixation
PubMed: 31488214
DOI: 10.1186/s40478-019-0799-y -
Clocks & Sleep May 2022Kleine-Levin syndrome (KLS) is characterized by episodes of hypersomnia. Additionally, these patients can present with hyperphagia, hypersexuality, abnormal behavior,... (Review)
Review
Kleine-Levin syndrome (KLS) is characterized by episodes of hypersomnia. Additionally, these patients can present with hyperphagia, hypersexuality, abnormal behavior, and cognitive dysfunction. Functional neuroimaging studies such as fMRI-BOLD, Positron Emission Tomography (PET) or SPECT help us understand the neuropathological bases of different disorders. We conducted a systematic review to investigate the neuroimaging features of KLS patients and their clinical correlations. This systematic review was conducted by following the Meta-Analysis of Observational Studies in Epidemiology (MOOSE) and PRISMA protocol reporting guidelines. We aim to investigate the clinical correlation with neuroimaging among patients with KLS. We included only studies written in the English language in the last 20 years, conducted on humans; 10 studies were included. We excluded systematic reviews, metanalysis, and case reports. We found that there are changes in functional imaging studies during the symptomatic and asymptomatic periods as well as in between episodes in patients with K.L.S. The areas most reported as affected were the hypothalamic and thalamic regions, which showed hypoperfusion and, in a few cases, hyperperfusion; areas such as the frontal, parietal, occipital and the prefrontal cortex all showed alterations in cerebral perfusion. These changes in cerebral blood flow and regions vary according to the imaging (SPECT, PET SCAN, or fMRI) and the task performed while imaging was performed. We encountered conflicting data between studies. Hyper insomnia, the main feature of this disease during the symptomatic periods, was associated with decreased thalamic activity. Other features of K.L.S., such as apathy, hypersexuality, and depersonalization, were also correlated with functional imaging changes. There were also findings that correlated with working memory deficits seen in this stage during the asymptomatic periods. Hyperactivity of the thalamus and hypothalamus were the main features shown during the asymptomatic period. Additionally, functional imaging tends to improve with a longer course of the disease, which suggests that K.L.S. patients outgrow the disease. These findings should caution physicians when analyzing and correlating neuroimaging findings with the disease.
PubMed: 35735605
DOI: 10.3390/clockssleep4020025 -
European Journal of Vascular and... Dec 2021Many techniques have been introduced to enable quantification of tissue perfusion in patients with peripheral arterial disease (PAD). Currently, none of these techniques...
OBJECTIVE
Many techniques have been introduced to enable quantification of tissue perfusion in patients with peripheral arterial disease (PAD). Currently, none of these techniques is widely used to analyse real time tissue perfusion changes during endovascular or surgical revascularisation procedures. The aim of this systematic review was to provide an up to date overview of the peri-procedural applicability of currently available techniques, diagnostic accuracy of assessing tissue perfusion and the relationship with clinical outcomes.
DATA SOURCES
MEDLINE, Embase, CINAHL, and the Cochrane Central Register of Controlled Trials.
REVIEW METHODS
This systematic review was conducted in accordance with the Preferred Reporting Items for Systematic review and Meta-Analysis (PRISMA) guidelines. Four electronic databases were searched up to 31 12 2020 for eligible articles: MEDLINE, Embase, CINAHL and the Cochrane Central Register of Controlled Trials. Eligible articles describing a perfusion measurement technique, used in a peri-procedural setting before and within 24 hours after the revascularisation procedure, with the aim of determining the effect of intervention in patients with PAD, were assessed for inclusion. The QUADAS-2 tool was used to assess the risk of bias and applicability of the studies.
RESULTS
An overview of 10 techniques found in 26 eligible articles focused on study protocols, research goals, and clinical outcomes is provided. Non-invasive techniques included laser speckle contrast imaging, micro-lightguide spectrophotometry, magnetic resonance imaging perfusion, near infrared spectroscopy, skin perfusion pressure, and plantar thermography. Invasive techniques included two dimensional perfusion angiography, contrast enhanced ultrasound, computed tomography perfusion imaging, and indocyanine green angiography. The results of the 26 eligible studies, which were mostly of poor quality according to QUADAS-2, were without exception, not sufficient to substantiate implementation in daily clinical practice.
CONCLUSION
This systematic review provides an overview of 10 tissue perfusion assessment techniques for patients with PAD. It seems too early to appoint one of them as a reference standard. The scope of future research in this domain should therefore focus on clinical accuracy, reliability, and validation of the techniques.
Topics: Diagnostic Techniques, Cardiovascular; Endovascular Procedures; Humans; Perfusion Imaging; Peripheral Arterial Disease; Predictive Value of Tests; Regional Blood Flow; Reproducibility of Results; Treatment Outcome; Vascular Surgical Procedures
PubMed: 34674935
DOI: 10.1016/j.ejvs.2021.08.017 -
European Stroke Journal Mar 2020The aim of this systematic review and meta-analysis is to determine the diagnostic accuracy of computed tomography brain perfusion in the prediction of haemorrhagic... (Review)
Review
Diagnostic accuracy of computed tomography perfusion in the prediction of haemorrhagic transformation and patient outcome in acute ischaemic stroke: A systematic review and meta-analysis.
PURPOSE
The aim of this systematic review and meta-analysis is to determine the diagnostic accuracy of computed tomography brain perfusion in the prediction of haemorrhagic transformation and patient outcome in acute ischaemic stroke.
METHOD
Electronic databases and grey literature published over the last 10 years related to healthcare and radiology were searched using the key terms: 'computed tomography perfusion', 'haemorrhagic transformation', 'acute ischaemic stroke', 'functional outcome' and their synonyms using both UK and American spellings. Inclusion criteria were: sample size at least 30 patients, original research, evaluate ability of computed tomography perfusion to predict haemorrhagic transformation, reports diagnostic accuracy or provide relevant data for a 2 × 2 contingency table, use follow-up non-contrast computed tomography (NCCT) or magnetic resonance imaging as reference standard.
FINDINGS
Twelve studies were included in the review; studies cover a total of 808 patients. Haemorrhagic transformation occurred in 30.2% of patients. Pooled sensitivity and specificity were 85.9% (95% CI; 65-97%), 73.9% (95% CI; 45-92%) and accuracy of 79.1% (95% CI; 57-98%). Pooled NPV was 92.9% with a high false positive rate (19.8%), which could be explained in terms of outcome classification, acquisition artefact and computed tomography perfusion processing algorithms.
DISCUSSION
This review evaluated the importance of using pre-defined threshold measurement for optimal prediction of HT, the relevance of patient pre-treatment clinical parameters to HT occurrence, the CTP parameters and the measurements that are independent predictors of HT, the significance of rtPA rather as an exacerbator of HT and the impact of both minor and major HT/PH on patient 2 functional outcome.
CONCLUSION
Computed tomography perfusion has a high sensitivity and moderately high specificity for prediction of haemorrhagic transformation in acute ischaemic stroke. Pre-treatment clinical decision making requires consideration of clinical factors in addition to imaging findings. This systematic review and meta-analysis highlights that pre-treatment computed tomography perfusion adds to clinical confidence by predicting potential for haemorrhage, both in thrombolysed and un-thrombolysed patients, and also influences decisions about alternative treatments for acute ischaemic stroke patients.
PubMed: 32232165
DOI: 10.1177/2396987319883461 -
Frontiers in Medicine 2022The staphylococcal enterotoxin C (SEC), a commercially available bio-product from (), has been widely used to control MPE.
INTRODUCTION
The staphylococcal enterotoxin C (SEC), a commercially available bio-product from (), has been widely used to control MPE.
OBJECTIVES
We designed and performed a new systematic review (SR) and meta-analysis to clarify the perfusion protocols with SEC, determine their clinical effectiveness and safety, and reveal the indication and optimum usage for achieving the desired responses.
METHODOLOGY
All randomized controlled trials (RCTs) about SEC for MPE were collected from electronic databases (from inception until July 2021), and clustered into multiple logical topics. grading of recommendation assessment, development, and evaluation (GRADE) approach.
RESULTS
All 114 were clustered into SEC alone or plus chemical agents. The SEC alone showed a better complete response (CR), a lower pleurodesis failure, and adverse drug reactions (ADRs), and a higher fever than cisplatin (DDP) alone. The SEC and chemical agents developed 10 perfusion protocols. . The SEC (100-200 ng per time, one time a week for one to four times) with DDP (30-40 mg, or 50-60 mg each time) significantly improved clinical responses for patients with moderate to large volume, Karnofsky performance status (KPS) scores ≥40, ≥50, or ≥60, and anticipated survival time (AST) ≥2 or 3 months. Most results were moderate to low quality.
CONCLUSION
Current pieces of evidence indicate that super-antigen SEC is a pleurodesis agent, which provides an attractive alternative to existing palliative modalities for patients with MPE. Among 10 protocols, the SEC and DDP perfusion is a most commonly used, which shows a significant improvement in clinical responses with low ADRs. These findings also a possible indication and optimal usage for SEC and DDP perfusion.
PubMed: 35547209
DOI: 10.3389/fmed.2022.816973 -
Journal of the Academy of... 2022Chronic cerebral hypoperfusion is a potential mechanism that causes cognitive impairment in patients with heart failure. Cognitive impairment in this population is... (Review)
Review
BACKGROUND
Chronic cerebral hypoperfusion is a potential mechanism that causes cognitive impairment in patients with heart failure. Cognitive impairment in this population is associated with an increased mortality and poorer quality of life. Understanding the etiopathogenesis of cognitive impairment is crucial to developing effective treatment. A left ventricular assist device (LVAD) is a durable mechanical circulatory support device that restores systemic perfusion in patients with heart failure, potentially reversing cerebral hypoperfusion and cognitive impairment.
OBJECTIVE
This case series and systematic review examines the effect of LVAD implantation on cognition in patients with heart failure.
METHODS
We report a case series of 4 LVAD recipients at a tertiary academic center who underwent preimplant and postimplant cognitive testing. We also conducted a systematic review of studies with adult recipients of a continuous-flow LVAD whose cognition was measured before and after implantation. We searched Medline, EMBASE, SCOPUS, and the Cochrane library (start of database to July 16, 2021) for longitudinal, peer-reviewed studies written in English.
RESULTS
Cognitive improvement after LVAD implantation was observed in the case series, with improvement on phonemic fluency and digit symbol coding assessments. Two out of 4 cases in the case series improved on Clinical Dementia Rating: one from moderate dementia to mild cognitive impairment and another from mild cognitive impairment to unimpaired. Seven studies were included in the systematic review and were heterogeneous regarding cognitive tests employed, follow-up period, and measured outcomes. Montreal Cognitive Assessment and Trail-Making Test Part B were used most commonly. Cognitive improvement was reported in all 7 studies with at least 1 study reporting statistically significant improvements in each the following cognitive domains: delayed and immediate recall, executive function, visuospatial function, verbal function, attention, and processing speed. Most studies had small sample sizes and lacked a control group.
CONCLUSIONS
LVAD implantation appears to be associated with improved cognition. Adequately powered, prospective studies are needed to examine the effect of LVAD on cognitive function in patients with heart failure. Additionally, studies that directly examine cerebral blood flow in conjunction with cognitive assessment are needed to establish the relationship between the reversal of cerebral hypoperfusion and improved cognition.
Topics: Adult; Humans; Heart-Assist Devices; Quality of Life; Heart Failure; Treatment Outcome; Cognition
PubMed: 36116764
DOI: 10.1016/j.jaclp.2022.09.003 -
Journal of Alzheimer's Disease Reports Apr 2020Nitric oxide/cyclic guanosine monophosphate (cGMP) signaling is compromised in Alzheimer's disease (AD), and phosphodiesterase 5 (PDE5), which degrades cGMP, is... (Review)
Review
Nitric oxide/cyclic guanosine monophosphate (cGMP) signaling is compromised in Alzheimer's disease (AD), and phosphodiesterase 5 (PDE5), which degrades cGMP, is upregulated. Sildenafil inhibits PDE5 and increases cGMP levels. Integrating previous findings, we determine that most doses of sildenafil (especially low doses) likely activate peroxisome proliferator-activated receptor-γ coactivator 1α (PGC1α) via protein kinase G-mediated cyclic adenosine monophosphate (cAMP) response element binding protein (CREB) phosphorylation and/or Sirtuin-1 activation and PGC1α deacetylation. Via PGC1α signaling, low-dose sildenafil likely suppresses β-secretase 1 expression and amyloid-β (Aβ) generation, upregulates antioxidant enzymes, and induces mitochondrial biogenesis. Plus, sildenafil should increase brain perfusion, insulin sensitivity, long-term potentiation, and neurogenesis while suppressing neural apoptosis and inflammation. A systematic review of sildenafil in AD was undertaken. sildenafil protected neural mitochondria from Aβ and advanced glycation end products. In transgenic AD mice, sildenafil was found to rescue deficits in CREB phosphorylation and memory, upregulate brain-derived neurotrophic factor, reduce reactive astrocytes and microglia, decrease interleukin-1β, interleukin-6, and tumor necrosis factor-α, decrease neural apoptosis, increase neurogenesis, and reduce tau hyperphosphorylation. All studies that tested Aβ levels reported significant improvements except the two that used the highest dosage, consistent with the dose-limiting effect of cGMP-induced phosphodiesterase 2 (PDE2) activation and cAMP depletion on PGC1α signaling. In AD patients, a single dose of sildenafil decreased spontaneous neural activity, increased cerebral blood flow, and increased the cerebral metabolic rate of oxygen. A randomized control trial of sildenafil (ideally with a PDE2 inhibitor) in AD patients is warranted.
PubMed: 32467879
DOI: 10.3233/ADR-200166 -
Annals of Palliative Medicine Feb 2022The application value of cerebral perfusion imaging, such as fluorodeoxyglucose-positron-emission computed tomography (FDG-PET), single-photon emission computed... (Meta-Analysis)
Meta-Analysis
Systematic review and meta-analysis of diagnostic test accuracy (DTA) studies: the role of cerebral perfusion imaging in prognosis evaluation of mild cognitive impairment.
BACKGROUND
The application value of cerebral perfusion imaging, such as fluorodeoxyglucose-positron-emission computed tomography (FDG-PET), single-photon emission computed tomography (SPECT), and structural magnetic resonance imaging (MRI), in the prognostic assessment of mild cognitive impairment (MCI) remains unclear. Thus, it was the focus of this meta-analysis, which aimed to provide a theoretical basis for early diagnosis of neurological diseases.
METHODS
The Boolean logic retrieval method was used to retrieve related literature, with "cognitive disorder", "cerebral perfusion imaging", "cerebral imaging", "mild cognitive impairment", and "prognostic assessment" as search terms. The PubMed, Medline, CNKI (China National Knowledge Infrastructure), and other databases were searched from the date of establishment of the database to December 30, 2020 for literature on the prognostic assessment of MCI using FDG-PET, SPECT, and MRI imaging. Meta-analysis was performed using Review Manager software.
RESULTS
A total of 16 references were identified, most of which had a low risk of bias (i.e. medium and high-quality). The meta-analysis results showed that the sensitivity and specificity of FDG-PET imaging was significantly higher than those of SPECT and MRI imaging, and the differences were statistically significant (P<0.05). The summary receiver operating characteristic (sROC) curves for the sensitivity and specificity of FDG-PET, SPECT, and MRI imaging did not present a "shoulder arm" distribution, and there was no threshold effect.
DISCUSSION
Cerebral perfusion imaging has good prognostic value for patients with MCI, and FDG-PET imaging has better predictive ability of the prognosis for patients with MCI.
Topics: Alzheimer Disease; Cerebrovascular Circulation; Cognitive Dysfunction; Diagnostic Tests, Routine; Humans; Magnetic Resonance Imaging; Prognosis; Radiopharmaceuticals
PubMed: 35249345
DOI: 10.21037/apm-21-3916