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BMC Pharmacology & Toxicology Sep 2014Cardiotoxicity is a serious side effect to treatment with 5-fluorouracil (5-FU), but the underlying mechanisms are not fully understood. The objective of this systematic... (Review)
Review
BACKGROUND
Cardiotoxicity is a serious side effect to treatment with 5-fluorouracil (5-FU), but the underlying mechanisms are not fully understood. The objective of this systematic review was to evaluate the pathophysiology of 5-FU- induced cardiotoxicity.
METHODS
We systematically searched PubMed for articles in English using the search terms: 5-FU OR 5-fluorouracil OR capecitabine AND cardiotoxicity. Papers evaluating the pathophysiology of this cardiotoxicity were included.
RESULTS
We identified 27 articles of 26 studies concerning the pathophysiology of 5-FU-induced cardiotoxicity. The studies demonstrated 5-FU-induced: hemorrhagic infarction, interstitial fibrosis and inflammatory reaction in the myocardium; damage of the arterial endothelium followed by platelet aggregation; increased myocardial energy metabolism and depletion of high energy phosphate compounds; increased superoxide anion levels and a reduced antioxidant capacity; vasoconstriction of arteries; changes in red blood cell (RBC) structure, function and metabolism; alterations in plasma levels of substances involved in coagulation and fibrinolysis and increased endothelin-1 levels and N-terminal-pro brain natriuretic peptide levels. Based on these findings the proposed mechanisms are: endothelial injury followed by thrombosis, increased metabolism leading to energy depletion and ischemia, oxidative stress causing cellular damage, coronary artery spasm leading to myocardial ischemia and diminished ability of RBCs to transfer oxygen resulting in myocardial ischemia.
CONCLUSIONS
There is no evidence for a single mechanism responsible for 5-FU-induced cardiotoxicity, and the underlying mechanisms might be multifactorial. Further research is needed to elucidate the pathogenesis of this side effect.
Topics: Animals; Antimetabolites, Antineoplastic; Fluorouracil; Heart; Humans
PubMed: 25186061
DOI: 10.1186/2050-6511-15-47 -
The Cochrane Database of Systematic... Jul 2013This is an update of a Cochrane Review first published in The Cochrane Library, Issue 2, 2008.The technique called one-lung ventilation can confine bleeding or infection... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
This is an update of a Cochrane Review first published in The Cochrane Library, Issue 2, 2008.The technique called one-lung ventilation can confine bleeding or infection to one lung, prevent rupture of a lung cyst or, more commonly, facilitate surgical exposure of the unventilated lung. During one-lung ventilation, anaesthesia is maintained either by delivering an inhalation anaesthetic to the ventilated lung or by infusing an intravenous anaesthetic. It is possible that the method chosen to maintain anaesthesia may affect patient outcomes. Inhalation anaesthetics may impair hypoxic pulmonary vasoconstriction (HPV) and increase intrapulmonary shunt and hypoxaemia.
OBJECTIVES
The objective of this review was to evaluate the effectiveness and safety of intravenous versus inhalation anaesthesia for one-lung ventilation.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL); The Cochrane Library (2012, Issue 11); MEDLINE (1966 to November 2012); EMBASE (1980 to November 2012); Literatura Latino-Americana e do Caribe em Ciências da Saúde (LILACS, 1982 to November 2012) and ISI web of Science (1945 to November 2012), reference lists of identified trials and bibliographies of published reviews. We also contacted researchers in the field. No language restrictions were applied. The date of the most recent search was 19 November 2012. The original search was performed in June 2006.
SELECTION CRITERIA
We included randomized controlled trials and quasi-randomized controlled trials of intravenous (e.g. propofol) versus inhalation (e.g. isoflurane, sevoflurane, desflurane) anaesthesia for one-lung ventilation in both surgical and intensive care participants. We excluded studies of participants who had only one lung (i.e. pneumonectomy or congenital absence of one lung).
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed trial quality and extracted data. We contacted study authors for additional information.
MAIN RESULTS
We included in this updated review 20 studies that enrolled 850 participants, all of which assessed surgical participants-no studies investigated one-lung ventilation performed outside the operating theatre. No evidence indicated that the drug used to maintain anaesthesia during one-lung ventilation affected participant outcomes. The methodological quality of the included studies was difficult to assess as it was reported poorly, so the predominant classification of bias was 'unclear'.
AUTHORS' CONCLUSIONS
Very little evidence from randomized controlled trials suggests differences in participant outcomes with anaesthesia maintained by intravenous versus inhalational anaesthesia during one-lung ventilation. If researchers believe that the type of drug used to maintain anaesthesia during one-lung ventilation is important, they should design randomized controlled trials with appropriate participant outcomes, rather than report temporary fluctuations in physiological variables.
Topics: Anesthesia, Inhalation; Anesthesia, Intravenous; Humans; One-Lung Ventilation; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 23846831
DOI: 10.1002/14651858.CD006313.pub3 -
Annals of Medicine and Surgery (2012) Mar 2024This study aimed to analyze the Vaccine Adverse Event Reporting System (VAERS) database and systematically review the literature to provide a comprehensive analysis of...
Reversible cerebral vasoconstriction syndrome and posterior reversible encephalopathy syndrome following vaccination: analysis of the VAERS database and systematic review.
OBJECTIVES
This study aimed to analyze the Vaccine Adverse Event Reporting System (VAERS) database and systematically review the literature to provide a comprehensive analysis of reversible cerebral vasoconstriction syndrome (RCVS) and posterior reversible encephalopathy syndrome (PRES) secondary to vaccination.
METHODS
The authors analyzed the VAERS database and conducted a systematic review following PRISMA guidelines. The inclusion criteria for VAERS data were a score of ≥3 on the RCVS score and/or radiographic findings consistent with the diagnosis of RCVS or PRES. The systematic review was registered with PROSPERO.
RESULTS
Our combined data set included 29 cases (9 RCVS and 20 PRES). Most cases were women (72.4%) with a mean age of 50.7 years (SD 19.4 years). Most cases were associated with COVID-19 mRNA vaccines (58.6% Moderna, 20.7% Pfizer). Hypertension (37.9%), hyperlipidemia (13.7%), chronic kidney disease (CKD) (10.3%), and end-stage renal disease (6.8%) were common comorbidities. Furthermore, 20.6% (6/29) of cases were on immunosuppression therapy for various reasons. The mean time to symptom onset was 10.49 days after vaccination (SD 18.60), and the mean duration of hospitalization was 7.42 days (SD 5.94). The symptoms reported the most frequently were headache (41.3%), elevated blood pressure (31.0%), and emesis (17.2%). Typical radiographic findings included T2/FLAIR hyperintensities affecting the parieto-occipital lobes, indicative of vasogenic and/or cytotoxic edema.
CONCLUSIONS
This study provides a comprehensive analysis of postvaccine RCVS and PRES. Both disease states were seen most often in those with pre-existing risk factors such as female sex, age over 50, hypertension, renal disease, and immunosuppression. Vaccines and their associated immune response may cause endothelial dysfunction leading to cerebral vasospasm and loss of cerebral autoregulation. However, further research is required to understand the underlying pathophysiological mechanisms. Despite the associations found, the absolute risk of these syndromes remains extremely low compared to the immense benefits of vaccination.
PubMed: 38463101
DOI: 10.1097/MS9.0000000000001407 -
International Urology and Nephrology Mar 2011Hepatorenal syndrome (HRS) is a common complication in patients with cirrhosis or fulminant liver failure. We systematically reviewed the benefits and harms of using... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Hepatorenal syndrome (HRS) is a common complication in patients with cirrhosis or fulminant liver failure. We systematically reviewed the benefits and harms of using terlipressin, a novel vasoconstricting agent in patients with HRS.
METHODS
We searched MEDLINE, SCOPUS, and conference proceedings for relevant trials of terlipressin. Results were summarized using the random-effects model.
RESULTS
Eight trials (320 participants) were included. When compared with placebo, terlipressin-treated patients had higher HRS reversal (odds ratio [OR] 7.47, 95% confidence interval [CI] 3.17-17.59), mean arterial pressure (weighted mean difference [WMD] 11.26 mmHg, 95% CI 1.52-21), and urine output. There was a significant increase in ischemic adverse events with terlipressin when compared to placebo. There was mild-to-moderate heterogeneity in these analyses. There was no significant difference between terlipressin and noradrenaline in HRS reversal (OR 1.23, 95% CI, 0.43-3.54), mean arterial pressure, and urine output. Side-effect profile did not differ between terlipressin and noradrenaline.
CONCLUSION
Terlipressin improves HRS reversal and other surrogate outcome measures compared with placebo, but no significant differences for these outcomes were noted when comparing terlipressin and noradrenaline. Terlipressin is a potential therapeutic option for HRS, but larger trials comparing terlipressin to other widely used vasoconstrictors are warranted.
Topics: Antihypertensive Agents; Diagnosis, Differential; Hepatorenal Syndrome; Humans; Liver Cirrhosis; Lypressin; Terlipressin; Treatment Outcome
PubMed: 20306131
DOI: 10.1007/s11255-010-9725-8 -
Journal of Neurology Jun 2023During the SARS-CoV2 pandemic, several cases of Posterior Reversible Encephalopathy Syndrome (PRES) and of Reversible Cerebral Vasoconstriction Syndrome (RCVS) in... (Review)
Review
Posterior reversible encephalopathy syndrome and reversible cerebral vasoconstriction syndrome in patients with COVID-19 infection: is there a link? A systematic review and case report analysis.
During the SARS-CoV2 pandemic, several cases of Posterior Reversible Encephalopathy Syndrome (PRES) and of Reversible Cerebral Vasoconstriction Syndrome (RCVS) in COVID-19 patients have been reported, but the link between these syndromes and COVID-19 is unclear. We performed a systematic review, according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement to evaluate whether SARS-CoV2 infection or the drugs used to treat it could be deemed potential risk factors for PRES or RCVS. We performed a literature search. We found 70 articles (60 on PRES and 10 on RCVS) concerning n = 105 patients (n = 85 with PRES, n = 20 with RCVS). We analyzed the clinical characteristics of the two populations separately, then performed an inferential analysis to search for other independent risk factors. We found fewer than usual PRES-related (43.9%) and RCVS-related (45%) risk factors in patients with COVID-19. Such a low incidence of risk factors for PRES and RCVS might suggest the involvement of COVID-19 as an additional risk factor for both diseases due to its capability to cause endothelial dysfunction. We discuss the putative mechanisms of endothelial damage by SARS-CoV2 and antiviral drugs which may underlie the development of PRES and RCVS.
Topics: Humans; Posterior Leukoencephalopathy Syndrome; COVID-19; Vasoconstriction; RNA, Viral; SARS-CoV-2; Cerebrovascular Disorders
PubMed: 37014421
DOI: 10.1007/s00415-023-11684-4 -
The Cochrane Database of Systematic... Oct 2004Pulmonary Hypertension (PH) can be either of unknown aetiology (primary pulmonary hypertension (PPH)) or due to a known underlying cause (secondary pulmonary... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Pulmonary Hypertension (PH) can be either of unknown aetiology (primary pulmonary hypertension (PPH)) or due to a known underlying cause (secondary pulmonary hypertension (SPH). Pulmonary arteriolar vasoconstriction is considered to be an important characteristic of PH. Therapies which aim to vasodilate are used to treat pulmonary hypertension.
OBJECTIVES
To determine the clinical efficacy of sildenafil, a vasodilator which works through inhibition of the enzyme phosphodiesterase type V (PDE5I), administered via any route to people with pulmonary hypertension in primary or secondary forms.
SEARCH STRATEGY
Electronic databases were searched with pre-defined search terms. Searches were current as of November 2003.
SELECTION CRITERIA
Randomised controlled trials were considered for inclusion in the review. We included studies which assessed the effects of sildenafil in participants with PPH and SPH.
DATA COLLECTION AND ANALYSIS
Two reviewers independently assessed and extracted data from clinical trials. Data were entered in RevMan Analyses 1.0.2. Continuous data were pooled with an estimate on either WMD (weighted mean difference) or SMD (standardised mean difference) scales. Dichotomous data were pooled and a RR (relative risk) was calculated.
MAIN RESULTS
Four studies recruiting 77 participants met the inclusion criteria of the review. Two studies assessed the acute effects of sildenafil. Two small crossover study assessed the effects of long term administration. The 'acute effect' studies indicated that sildenafil has a pulmonary vasodilatory effect. The two crossover studies showed improvement in symptoms. One study showed improvement in fatigue domains from a validated health status questionnaire. Both crossover studies reported that the drug was well tolerated.
REVIEWERS' CONCLUSIONS
The validity of the observed effects is undermined by small participant numbers and inadequate exploration of the different disease etiologies. The effects on long term outcome such as NYHA functional class, symptoms, mortality and exercise capacity require further validation. More studies of adequate size are required before the long term effects of sildenafil on clinically important outcomes can be established.
Topics: 3',5'-Cyclic-GMP Phosphodiesterases; Humans; Hypertension, Pulmonary; Piperazines; Purines; Randomized Controlled Trials as Topic; Sildenafil Citrate; Sulfones; Vasodilator Agents
PubMed: 15495058
DOI: 10.1002/14651858.CD003562.pub2 -
Journal of the American Heart... Jan 2016Radial artery occlusion (RAO) may occur posttransradial intervention and limits the radial artery as a future access site, thus precluding its use as an arterial... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Radial artery occlusion (RAO) may occur posttransradial intervention and limits the radial artery as a future access site, thus precluding its use as an arterial conduit. In this study, we investigate the incidence and factors influencing the RAO in the current literature.
METHODS AND RESULTS
We searched MEDLINE and EMBASE for studies of RAO in transradial access. Relevant studies were identified and data were extracted. Data were synthesized by meta-analysis, quantitative pooling, graphical representation, or by narrative synthesis. A total of 66 studies with 31 345 participants were included in the analysis. Incident RAO ranged between <1% and 33% and varied with timing of assessment of radial artery patency (incidence of RAO within 24 hours was 7.7%, which decreased to 5.5% at >1 week follow-up). The most efficacious measure in reducing RAO was higher dose of heparin, because lower doses of heparin were associated with increased RAO (risk ratio 0.36, 95% CI 0.17-0.76), whereas shorter compression times also reduced RAO (risk ratio 0.28, 95% CI 0.05-1.50). Several factors were found to be associated with RAO including age, sex, sheath size, and diameter of radial artery, but these factors were not consistent across all studies.
CONCLUSIONS
RAO is a common complication of transradial access. Maintenance of radial patency should be an integral part of all procedures undertaken through the radial approach. High-dose heparin along with shorter compression times and patent hemostasis is recommended in reducing RAO.
Topics: Aged; Anticoagulants; Arterial Occlusive Diseases; Catheterization, Peripheral; Chi-Square Distribution; Dose-Response Relationship, Drug; Female; Heparin; Humans; Incidence; Male; Middle Aged; Odds Ratio; Punctures; Radial Artery; Risk Factors; Vasoconstriction
PubMed: 26811162
DOI: 10.1161/JAHA.115.002686 -
International Journal of Chronic... 2020Exacerbations of chronic obstructive pulmonary disease (COPD) are currently diagnosed based on changes in respiratory symptoms. Characterizing the imaging manifestation... (Review)
Review
Exacerbations of chronic obstructive pulmonary disease (COPD) are currently diagnosed based on changes in respiratory symptoms. Characterizing the imaging manifestation of exacerbations could be useful for objective diagnosis of exacerbations in the clinic and clinical trials, as well as provide a mechanism for monitoring exacerbation treatment and recovery. In this systematic review, we employed a comprehensive search across three databases (Medline, EMBASE, Web of Science) to identify studies that performed imaging of the thorax at COPD exacerbation. We included 51 from a total of 5,047 articles which met all our inclusion criteria. We used an adapted version of the Modified Newcastle-Ottawa Quality Assessment Scale for cohort studies to assess the quality of the included studies. Conclusions were weighted towards higher-quality articles. We identified a total of 36 thoracic imaging features studied at exacerbation of COPD. Studies were generally heterogeneous in their measurements and focus. Nevertheless, considering studies which performed consecutive imaging at stable state and exacerbation, which scored highest for quality, we identified salient imaging biomarkers of exacerbations. An exacerbation is characterized by airway wall and airway calibre changes, hyperinflation, pulmonary vasoconstriction and imaging features suggestive of pulmonary arterial hypertension. Most information was gained from CT studies. We present the first ever composite imaging signature of COPD exacerbations. While imaging during an exacerbation is comparatively new and not comprehensively studied, it may uncover important insights into the acute pathophysiologic changes in the cardiorespiratory system during exacerbations of COPD, providing objective confirmation of events and a biomarker of recovery and treatment response.
Topics: Disease Progression; Humans; Pulmonary Disease, Chronic Obstructive
PubMed: 32801677
DOI: 10.2147/COPD.S250746 -
The Journal of Headache and Pain Aug 2014There are many potential causes of sudden and severe headache (thunderclap headache), the most important of which is aneurysmal subarachnoid haemorrhage. Published... (Review)
Review
BACKGROUND
There are many potential causes of sudden and severe headache (thunderclap headache), the most important of which is aneurysmal subarachnoid haemorrhage. Published academic reviews report a wide range of causes. We sought to create a definitive list of causes, other than aneurysmal subarachnoid haemorrhage, using a systematic review.
METHODS
Systematic Review of EMBASE and MEDLINE databases using pre-defined search criteria up to September 2009. We extracted data from any original research paper or case report describing a case of someone presenting with a sudden and severe headache, and summarized the published causes.
RESULTS
Our search identified over 21,000 titles, of which 1224 articles were scrutinized in full. 213 articles described 2345 people with sudden and severe headache, and we identified 6 English language academic review articles. A total of 119 causes were identified, of which 46 (38%) were not mentioned in published academic review articles. Using capture-recapture analysis, we estimate that our search was 98% complete. There is only one population-based estimate of the incidence of sudden and severe headache at 43 cases per 100,000. In cohort studies, the most common causes identified were primary headaches or headaches of uncertain cause. Vasoconstriction syndromes are commonly mentioned in case reports or case series. The most common cause not mentioned in academic reviews was pneumocephalus. 70 non-English language articles were identified but these did not contain additional causes.
CONCLUSIONS
There are over 100 different published causes of sudden and severe headache, other than aneurysmal subarachnoid haemorrhage. We have now made a definitive list of causes for future reference which we intend to maintain. There is a need for an up to date population based description of cause of sudden and severe headache as the modern epidemiology of thunderclap headache may require updating in the light of research on cerebral vasoconstriction syndromes.
Topics: Cerebrovascular Disorders; Headache Disorders, Primary; Humans; Vasoconstriction
PubMed: 25123846
DOI: 10.1186/1129-2377-15-49 -
The Cochrane Database of Systematic... 2000Because hyperventilation is often associated with a rapid fall in intracranial pressure, it has been assumed to be effective in the treatment of severe head injury.... (Review)
Review
BACKGROUND
Because hyperventilation is often associated with a rapid fall in intracranial pressure, it has been assumed to be effective in the treatment of severe head injury. Hyperventilation reduces raised intracranial pressure by causing cerebral vasoconstriction and a reduction in cerebral blood flow. Whether reduced cerebral blood flow improves neurological outcome however, is unclear.
OBJECTIVES
To quantify the effect of hyperventilation on death and neurological disability following head injury.
SEARCH STRATEGY
The search strategy drew on that of the Injuries Group as a whole. The reference lists of all relevant articles identified were checked and the first author of reports was contacted to ask for assistance in identifying any further trials. Most recent search was done in September 1999.
SELECTION CRITERIA
All randomised trials of hyperventilation, in which study participants had a clinically defined acute traumatic head injury of any severity. There were no language restrictions.
DATA COLLECTION AND ANALYSIS
We collected data on the participants, the timing and duration of the intervention, duration of follow up, neurological disability and death. Relative risks (RR) and 95% confidence intervals were calculated for each trial on an intention to treat basis. Timing, degree and duration of hyperventilation were identified a-priori as potential sources of heterogeneity between trials.
MAIN RESULTS
One trial of 113 participants was identified. Hyperventilation alone, as well as in conjunction with the buffer THAM showed a beneficial effect on mortality at one year after injury, although the effect measure was imprecise (RR=0.73; 95% CI 0.36;1.49 and RR=0.89; 95% CI 0.47;1.72 respectively). This improvement in outcome was not supported by an improvement in neurological recovery. For hyperventilation alone, the RR for death or severe disability was 1. 14 (95% CI 0.82;1.58). The RR for death or severe disability in the hyperventilation plus THAM group, was 0.87 (95% CI 0.58;1.28).
REVIEWER'S CONCLUSIONS
The data available are inadequate to assess any potential benefit or harm that might result from hyperventilation in severe head injury. Randomised controlled trials to assess the effectiveness of hyperventilation therapy following severe head injury are needed.
Topics: Brain Injuries; Humans; Hyperventilation; Respiration, Artificial
PubMed: 10796728
DOI: 10.1002/14651858.CD000566