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Neuropathology and Applied Neurobiology Apr 2022The pathological processes leading to synapse loss, neuronal loss, brain atrophy and gliosis in Alzheimer's disease (AD) and their relation to vascular disease and... (Review)
Review
The pathological processes leading to synapse loss, neuronal loss, brain atrophy and gliosis in Alzheimer's disease (AD) and their relation to vascular disease and immunological changes are yet to be fully explored. Amyloid-β (Aβ) aggregation, vascular damage and altered immune response interact at the blood-brain barrier (BBB), affecting the brain endothelium and fuelling neurodegeneration. The aim of the present systematic literature review was to critically appraise and to summarise the published evidence on the clinical correlations and pathophysiological concepts of BBB damage in AD, focusing on human data. The PubMed, Cochrane, Medline and Embase databases were searched for original research articles, systematic reviews and meta-analyses, published in English language from 01/2000 to 07/2021, using the keywords Alzheimer*, amyloid-β or β-amyloid or abeta and BBB. This review shows that specific changes of intercellular structures, reduced expression of transendothelial carriers, induction of vasoactive mediators and activation of both astroglia and monocytes/macrophages characterise BBB damage in human AD and AD models. BBB dysfunction on magnetic resonance imaging takes place early in the disease course in AD-specific brain regions. The toxic effects of Aβ and apolipoprotein E (ApoE) are likely to induce a non-cerebral-amyloid-angiopathy-related degeneration of endothelial cells, independently of cerebrovascular disease; however, some of the observed structural changes may just arise with age. Small vessel disease, ApoE, loss of pericytes, proinflammatory signalling and cerebral amyloid angiopathy enhance BBB damage. Novel therapeutic approaches for AD, including magnetic resonance-guided focused ultrasound, aim to open the BBB, potentially leading to an improved drainage of Aβ along perivascular channels and increased elimination from the brain. In vitro treatments with ApoE-modifying agents yielded promising effects on modulating BBB function. Reducing cardiovascular risk factors represents one of the most promising interventions for dementia prevention at present. However, further research is needed to elucidate the connection of BBB damage and tau pathology, the role of proinflammatory mediators in draining macromolecules and cells from the cerebral parenchyma, including their contribution to cerebral amyloid angiopathy. Improved insight into these pathomechanisms may allow to shed light on the role of Aβ deposition as a primary versus a secondary event in the complex pathogenesis of AD.
Topics: Alzheimer Disease; Amyloid beta-Peptides; Blood-Brain Barrier; Brain; Cerebral Amyloid Angiopathy; Endothelial Cells; Humans
PubMed: 34823269
DOI: 10.1111/nan.12782 -
The Cochrane Database of Systematic... Jun 2022There are many accepted airway clearance techniques (ACTs) for managing the respiratory health of people with cystic fibrosis (CF); none of which demonstrate... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
There are many accepted airway clearance techniques (ACTs) for managing the respiratory health of people with cystic fibrosis (CF); none of which demonstrate superiority. Other Cochrane Reviews have reported short-term effects related to mucus transport, but no evidence supporting long-term benefits. Exercise is an alternative ACT thought to produce shearing forces within the lung parenchyma, which enhances mucociliary clearance and the removal of viscous secretions. Recent evidence suggests that some people with CF are using exercise as a substitute for traditional ACTs, yet there is no agreed recommendation for this. Additionally, one of the top 10 research questions identified by people with CF is whether exercise can replace other ACTs. Systematically reviewing the evidence for exercise as a safe and effective ACT will help people with CF decide whether to incorporate this strategy into their treatment plans and potentially reduce their treatment burden. The timing of this review is especially pertinent given the shifting landscape of CF management with the advent of highly-effective small molecule therapies, which are changing the way people with CF are cared for.
OBJECTIVES
To compare the effect of exercise to other ACTs for improving respiratory function and other clinical outcomes in people with CF and to assess the potential adverse effects associated with this ACT.
SEARCH METHODS
On 28 February 2022, we searched the Cochrane Cystic Fibrosis Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. We also searched the reference lists of relevant articles and reviews. We searched online clinical trial registries on 15 February 2022. We emailed authors of studies awaiting classification or potentially eligible abstracts for additional information on 1 February 2021.
SELECTION CRITERIA
We selected randomised controlled studies (RCTs) and quasi-RCTs comparing exercise to another ACT in people with CF for at least two treatment sessions.
DATA COLLECTION AND ANALYSIS
Two review authors independently extracted data and assessed risk of bias for the included studies. They assessed the certainty of the evidence using GRADE. Review authors contacted investigators for further relevant information regarding their publications.
MAIN RESULTS
We included four RCTs. The 86 participants had a wide range of disease severity (forced expiratory volume in one second (FEV) ranged from 54% to 95%) and were 7 to 41 years old. Two RCTs were cross-over and two were parallel in design. Participants in one RCT were hospitalised with an acute respiratory exacerbation, whilst the participants in three RCTs were clinically stable. All four RCTs compared exercise either alone or in combination with another ACT, but these were too diverse to allow us to combine results. The certainty of the evidence was very low; we downgraded it due to low participant numbers and high or unclear risks of bias across all domains. Exercise versus active cycle of breathing technique (ACBT) One cross-over trial (18 participants) compared exercise alone to ACBT. There was no change from baseline in our primary outcome FEV, although it increased in the exercise group before returning to baseline after 30 minutes; we are unsure if exercise affected FEV as the evidence is very low-certainty. Similar results were seen for other measures of lung function. No adverse events occurred during the exercise sessions (very low-certainty evidence). We are unsure if ACBT was perceived to be more effective or was the preferred ACT (very low-certainty evidence). 24-hour sputum volume was less in the exercise group than with ACBT (secondary outcome). Exercise capacity, quality of life, adherence, hospitalisations and need for additional antibiotics were not reported. Exercise plus postural drainage and percussion (PD&P) versus PD&P only Two trials (55 participants) compared exercise and PD&P to PD&P alone. At two weeks, one trial narratively reported a greater increase in FEV % predicted with PD&P alone. At six months, the other trial reported a greater increase with exercise combined with PD&P, but did not provide data for the PD&P group. We are uncertain whether exercise with PD&P improves FEV as the certainty of evidence is very low. Other measures of lung function did not show clear evidence of effect. One trial reported no difference in exercise capacity (maximal work rate) after two weeks. No adverse events were reported (1 trial, 17 participants; very low-certainty evidence). Adherence was high, with all PD&P sessions and 96% of exercise sessions completed (1 trial, 17 participants; very low-certainty evidence). There was no difference between groups in 24-hour sputum volume or in the mean duration of hospitalisation, although the six-month trial reported fewer hospitalisations due to exacerbations in the exercise and PD&P group. Quality of life, ACT preference and need for antibiotics were not reported. Exercise versus underwater positive expiratory pressure (uPEP) One trial (13 participants) compared exercise to uPEP (also known as bubble PEP). No adverse events were recorded in either group (very low-certainty evidence). Trial investigators reported that participants perceived exercise as more fatiguing but also more enjoyable than bubble PEP (very low-certainty evidence). There were no differences found in the total weight of sputum collected during treatment sessions. The trial did not report the primary outcomes (FEV, quality of life, exercise capacity) or the secondary outcomes (other measures of lung function, adherence, need for antibiotics or hospitalisations).
AUTHORS' CONCLUSIONS
As one of the top 10 research questions identified by clinicians and people with CF, it is important to systematically review the literature regarding whether or not exercise is an acceptable and effective ACT, and whether it can replace traditional methods. We identified an insufficient number of trials to conclude whether or not exercise is a suitable alternative ACT, and the diverse design of included trials did not allow for meta-analysis of results. The evidence is very low-certainty, so we are uncertain about the effectiveness of exercise as an ACT. Longer studies examining outcomes that are important to people with CF are required to answer this question.
Topics: Adolescent; Adult; Anti-Bacterial Agents; Child; Cystic Fibrosis; Drainage, Postural; Forced Expiratory Volume; Humans; Mucociliary Clearance; Young Adult
PubMed: 35731672
DOI: 10.1002/14651858.CD013285.pub2 -
European Journal of Radiology Feb 2019To systematically review the clinical manifestations, MRI appearance, and management of tumefactive Virchow-Robin spaces (VRs).
OBJECTIVE
To systematically review the clinical manifestations, MRI appearance, and management of tumefactive Virchow-Robin spaces (VRs).
METHODS
A systematic MEDLINE literature search was performed. Data were extracted per tumefactive VRs location (type 1: along lenticulostriate arteries entering the basal ganglia; type 2: along perforating medullary arteries; type 3: mesencephalothalamic region; and other locations).
RESULTS
Ninety-nine articles were included, comprising 164 patients. There were few reports on type 1 tumefactive VRs (n = 5 patients) and tumefactive VRs at other locations (n = 16 patients). In type 2 tumefactive VRs (n = 62 patients), clinical manifestations were reported in 12.9%, signal abnormalities of adjacent brain parenchyma were reported in 32.3%, and MRI follow-up of 23/24 asymptomatic tumefactive VRs showed no change (mean follow-up of 3.2 years). In type 3 tumefactive VRs (n = 80 patients), clinical manifestations were reported in 75.0%, signal abnormalities inside VRs or adjacent brain parenchyma were reported in 3.8%, and neurosurgical outcome (59 reported patients) was generally good. Type 3 tumefactive VRs may increase after neurosurgery (5/59 [8.5%] reported patients; 0.5-14 years follow-up) or spontaneously (2/5 [40%] reported patients; 2 and 9 years follow-up), requiring (repeated) neurosurgery.
CONCLUSION
In type 2 tumefactive VRs, clinical manifestations and signal abnormalities of adjacent brain parenchyma occur in a minority of cases, and follow-up of asymptomatic patients seems unnecessary. In type 3 tumefactive VRs, clinical manifestations are common, concomitant signal abnormalities occur infrequently, and neurosurgical outcome is generally good. Follow-up of type 3 tumefactive VRs is suggested. There are limited data on other types of tumefactive VRs.
Topics: Arteries; Dilatation, Pathologic; Glymphatic System; Humans; Magnetic Resonance Imaging; Reproducibility of Results
PubMed: 30691661
DOI: 10.1016/j.ejrad.2018.12.011 -
Der Urologe. Ausg. A Jan 2020Robot-assisted surgery has become widely adopted in urology due to advantages in comparison with laparoscopic or open approaches. Robot-assisted living kidney...
BACKGROUND
Robot-assisted surgery has become widely adopted in urology due to advantages in comparison with laparoscopic or open approaches. Robot-assisted living kidney transplantation is one of the most challenging procedures in urology regarding technical, but also psychological and ethical aspects, and is currently routinely performed in two German departments.
OBJECTIVES
The goal was to analyze and compare current evidence and experiences of robot-assisted living kidney transplantation in Europe and in Germany.
MATERIALS AND METHODS
A systematic search was performed to identify relevant publications. They were compared with latest results from two German academic centers (Halle and Homburg/Saar).
RESULTS
In 2015, robot-assisted living kidney transplantation was performed for the first time in Europe. Since then, 8 academic centers have established this procedure. Until today, more than 180 robot-assisted kidney transplantations have been performed. Short- and mid-term results have proven to be excellent with low complication rates. Apart from 3 transplant losses because of arterial thrombosis and 5 surgical re-explorations due to hematoma, no other noteworthy complications occurred. There was only 1 lymphocele. The median blood loss was 150 ml and kidney function after 1 year was unchanged in comparison with postoperative day 30.
CONCLUSIONS
Robot-assisted living kidney transplantation is not inferior to the open approach. Even superiority is not unlikely because problematic situations such as obese patients or complex vascular anatomy can be handled safely. In particular, the development of lymphocele and wound healing disorders appear to be significantly decreased compared to conventional surgery.
Topics: Europe; Germany; Humans; Kidney Transplantation; Laparoscopy; Living Donors; Robotic Surgical Procedures
PubMed: 31832746
DOI: 10.1007/s00120-019-01085-9 -
Cureus Oct 2023Muco-obstructive lung disease is a new classification under the diseases of respiratory tract. A lot of discussion is still going on regarding this new group of... (Review)
Review
Muco-obstructive lung disease is a new classification under the diseases of respiratory tract. A lot of discussion is still going on regarding this new group of diseases. It is characterised by obstruction of the respiratory tract with a thick mucin layer. Usually in normal individuals, the mucus is swept out of the respiratory system while coughing in the form of sputum or phlegm, but if the consistency of the mucus is thick, or the amount is heavy or there is a certain defect in the ciliary function of the respiratory tract, the mucus is not cleared and it gets accumulated in the lungs alveoli, therefore blocking it. The mucus trapped in the distal airways cannot be cleared by coughing therefore forming a layer in the alveoli and bronchioles. Long-standing condition causes inflammation and infection. This new group of diseases specifically includes chronic obstructive pulmonary disease (COPD), cystic fibrosis (CF), primary ciliary dyskinesia (PCD) and non-cystic fibrosis bronchiectasis (NCFB). Asthma, although an obstructive disease of the lung, is not particularly included under muco-obstructive lung disease. The major symptoms with which these diseases present are sputum production, chronic cough and acute exacerbations of the condition. The mucus adheres to the lung parenchyma causing airway obstruction and hyperinflation. In this article, we will see how muco-obstructive lung diseases affect the normal physiology of the respiratory system and how is it different from other obstructive and restrictive lung diseases. We will individually look into all the four conditions that come under the category of muco-obstructive lung diseases.
PubMed: 37954759
DOI: 10.7759/cureus.46866 -
Surgical Endoscopy May 2024Ultrasound has been nicknamed "the surgeon's stethoscope". The advantages of laparoscopic ultrasound beyond a substitute for the sense of touch are considerable,... (Review)
Review
INTRODUCTION
Ultrasound has been nicknamed "the surgeon's stethoscope". The advantages of laparoscopic ultrasound beyond a substitute for the sense of touch are considerable, especially for robotic surgery. Being able to see through parenchyma and into vascular structures enables to avoid unnecessary dissection by providing a thorough assessment at every stage without the need for contrast media or ionising radiation. The limitations of restricted angulation and access within the abdominal cavity during laparoscopy can be overcome by robotic handling of miniaturised ultrasound probes and the use of various and specific frequencies will meet tissue- and organ-specific characteristics. The aim of this systematic review was to assess the reported applications of intraoperative ultrasound-guided robotic surgery and to outline future perspectives.
METHODS
The study adhered to the PRISMA guidelines. PubMed, Google Scholar, ScienceDirect and ClinicalTrials.gov were searched up to October 2023. Manuscripts reporting data on ultrasound-guided robotic procedures were included in the qualitative analysis.
RESULTS
20 studies met the inclusion criteria. The majority (53%) were related to the field of general surgery during liver, pancreas, spleen, gallbladder/bile duct, vascular and rectal surgery. This was followed by other fields of oncological surgery (42%) including urology, lung surgery, and retroperitoneal lymphadenectomy for metastases. Among the studies, ten (53%) focused on locating tumoral lesions and defining resection margins, four (15%) were designed to test the feasibility of robotic ultrasound-guided surgery, while two (10.5%) aimed to compare robotic and laparoscopic ultrasound probes. Additionally two studies (10.5%) evaluated the robotic drop-in probe one (5%) assessed the hepatic tissue consistency and another one (5%) aimed to visualize the blood flow in the splenic artery.
CONCLUSION
The advantages of robotic instrumentation, including ergonomics, dexterity, and precision of movements, are of relevance for robotic intraoperative ultrasound (RIOUS). The present systematic review demonstrates the virtue of RIOUS to support surgeons and potentially reduce minimally invasive procedure times.
Topics: Robotic Surgical Procedures; Humans; Ultrasonography, Interventional; Laparoscopy
PubMed: 38512350
DOI: 10.1007/s00464-024-10772-4 -
European Journal of Gastroenterology &... Feb 2017Radioembolization (RE) is a relatively novel treatment modality for primary and secondary hepatic malignancies. Microspheres embedded with a β-emitting radioisotope are... (Review)
Review
Radioembolization (RE) is a relatively novel treatment modality for primary and secondary hepatic malignancies. Microspheres embedded with a β-emitting radioisotope are injected into the hepatic artery, resulting in microsphere deposition in the tumor arterioles and normal portal triads. Microsphere deposition in nontumorous parenchyma can result in radiation-induced liver injury, with lethal RE-induced liver disease (REILD) at the outer end of the spectrum. The primary aim of this study was to evaluate RE-related hepatotoxicity and present an overview of the currently applied definitions and clinically relevant characteristics of REILD. A systematic literature search on REILD was performed. Studies after the introduction of the term REILD (2008) were screened for definitions of REILD. Hepatotoxicity and applied definitions of REILD were compared. Liver biochemistry test abnormalities occur in up to 100% of patients after RE, mostly self-limiting. The incidence of symptomatic REILD varied between 0 and 31%, although in most reports, the incidence was 0-8%, with a lethal outcome in 0-5%. With the exception of bilirubin, the presentation of hepatotoxicity and REILD was similar for cirrhotic and noncirrhotic patients. No uniform definition of REILD was established in the current literature. Here, we propose a unifying definition and grading system for REILD. RE-related hepatotoxicity is a common phenomenon; symptomatic REILD, however, is rare. Currently, reporting of REILD is highly variable, precluding reliable comparison between studies, identification of risk factors, and treatment developments.
Topics: Carcinoma, Hepatocellular; Embolization, Therapeutic; Humans; Liver Diseases; Liver Neoplasms; Microspheres; Radiation Injuries; Radiopharmaceuticals; Radiotherapy; Yttrium Radioisotopes
PubMed: 27926660
DOI: 10.1097/MEG.0000000000000772 -
Clinical Radiology Jun 2023To determine the feasibility of spectral computed tomography (CT) in the differentiation of focal liver lesions from hepatocellular carcinoma (HCC) using a network... (Meta-Analysis)
Meta-Analysis
AIM
To determine the feasibility of spectral computed tomography (CT) in the differentiation of focal liver lesions from hepatocellular carcinoma (HCC) using a network meta-analysis (NMA).
MATERIALS AND METHODS
The review was completed in accordance with PRISMA guidelines. Searches of three medical databases were performed. A total of nine articles were found for the qualitative synthesis. The meta-analysis was performed on five studies for the normalised iodine concentration (NIC; which is the iodine concentration in the lesion divided by the iodine concentration in the aorta) and the lesion-normal parenchyma iodine ratio (LNR; which is the iodine concentration in the lesion divided by the iodine concentration in the non-tumour hepatic parenchyma) on portal venous and arterial phase images due to sufficient data.
RESULTS
Spectral CT can be used to differentiate HCC from hepatic haemangioma (HH), focal nodular hyperplasia (FNH), regenerative nodules, neuroendocrine tumours (NETs), abscesses, and angiomyolipoma (AML). Hepatic metastases versus abscess and FNH versus HH could also be differentiated. The NMA demonstrated that HCC, NETs, and regenerative nodules could be differentiated due to lower quantitative iodine values. FNH, AML, and HH all had higher values.
CONCLUSION
Spectral CT shows promise in differentiating focal liver lesions. Studies with larger sample sizes are warranted. Future studies should be performed comparing benign lesions using quantitative markers.
Topics: Humans; Carcinoma, Hepatocellular; Liver Neoplasms; Contrast Media; Diagnosis, Differential; Tomography, X-Ray Computed; Liver; Iodine; Focal Nodular Hyperplasia; Angiomyolipoma; Hemangioma; Leukemia, Myeloid, Acute
PubMed: 37019736
DOI: 10.1016/j.crad.2023.02.017 -
Cancers May 2023For decades, lung surgery in thoracic cancer has evolved in two ways: saving more parenchyma and being minimally invasive. Saving parenchyma is a fundamental principle... (Review)
Review
For decades, lung surgery in thoracic cancer has evolved in two ways: saving more parenchyma and being minimally invasive. Saving parenchyma is a fundamental principle of surgery. However, minimally invasive surgery (MIS) is a matter of approach, so it has to do with advances in surgical techniques and tools. For example, MIS has become possible with the introduction of VATS (video-assisted thoracic surgery), and the development of tools has extended the indication of MIS. Especially, RATS (robot-assisted thoracic surgery) improved the quality of life for patients and the ergonomics of doctors. However, the dichotomous idea that the MIS is new and right but the open thoracotomy is old and useless may be inappropriate. In fact, MIS is exactly the same as a classic thoracotomy in that it removes the mass/parenchyma containing cancer and mediastinal lymph nodes. Therefore, in this study, we compare randomized-controlled trials about open thoracotomy and MIS to find out which surgical method is more helpful.
PubMed: 37174096
DOI: 10.3390/cancers15092630 -
International Journal of Surgery... Jan 2015Hepatic resection for malignancy is limited by the amount of liver parenchyma left behind. As a result, two-staged hepatectomy and portal vein occlusion (PVO) have... (Review)
Review
INTRODUCTION
Hepatic resection for malignancy is limited by the amount of liver parenchyma left behind. As a result, two-staged hepatectomy and portal vein occlusion (PVO) have become part of the treatment algorithm. Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) has been recently described as a method to stimulate rapid and profound hypertrophy.
MATERIALS AND METHODS
A systematic review of the literature pertaining to ALPPS was undertaken. Peer-reviewed articles relating to portal vein ligation (PVL) and in situ split (ISS) of the parenchyma were included.
RESULTS
To date, ALPPS has been employed for a variety of primary and metastatic liver tumors. In early case series, the perioperative morbidity and mortality was unacceptably high. However with careful patient selection and improved technique, many centers have reported a 0% 90-day mortality. The benefits of ALPPS include hypertrophy of 61-93% over a median 9-14 days, 95-100% completion of the second stage, and high likelihood of R0 resection (86-100%).
DISCUSSION
ALPPS is only indicated when a two-stage hepatectomy is necessary and the future liver remnant (FLR) is deemed inadequate (<30%). Use in patients with poor functional status, or advanced age (>70 years) is cautioned. Discretion should be used when considering this in patients with pathology other than colorectal liver metastases (CRLM), especially hilar tumors requiring biliary reconstruction. Biliary ligation during the first stage and routine lymphadenectomy of the hepatoduodenal ligament should be avoided.
CONCLUSIONS
A consensus on the indications and contraindications for ALPPS and a standardized operative protocol are needed.
Topics: Hepatectomy; Humans; Hypertrophy; Ligation; Liver; Liver Neoplasms; Liver Regeneration; Patient Selection; Portal Vein; Vascular Surgical Procedures
PubMed: 25496851
DOI: 10.1016/j.ijsu.2014.12.008