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Oncotarget Jul 2016To systematically review the safety and efficacy of lenvatinib in the treatment of patients, we retrieved all the relevant clinical trials on the adverse events (AEs)... (Meta-Analysis)
Meta-Analysis Review
To systematically review the safety and efficacy of lenvatinib in the treatment of patients, we retrieved all the relevant clinical trials on the adverse events (AEs) and survival outcomes of lenvatinib through PubMed, Medline, Embase, Web of Science and Cochrane Collaboration's Central register of controlled trial. Fourteen eligible studies involving a total of 978 patients were included in our analysis. The most common all-grade AEs observed in patients treated with lenvatinib were hematuria (56.6%), fatigue (52.2%) and decreased appetite (50.5%). The most frequently observed grade ≥3 AEs were thrombocytopenia (25.4%), hypertension (17.7%) and edema peripheral (15.5%). The incidences of both all-grade and high-grade hypertension were significantly increased. Meanwhile, the controlled trial suggested that progression free survival (PFS) was significantly longer in the lenvatinib group than the placebo group. Subgroup analyses showed that mean PFS for renal cell carcinoma was 10.933±1.828 months (95% CI 7.350-14.515, p < 0.001), and that for thyroid cancer was 18.344±0.083 months (95% CI 18.181-18.506, p < 0.001). In conclusion, lenvatinib is an effective agent in thyroid cancer. Early monitoring and effective management of side effects are crucial for the safe use of this drug.
Topics: Antineoplastic Agents; Disease-Free Survival; Fatigue; Hematuria; Humans; Hypertension; Neoplasms; Phenylurea Compounds; Quinolines; Thrombocytopenia; Treatment Outcome
PubMed: 27329593
DOI: 10.18632/oncotarget.10019 -
International Journal of Molecular... Aug 2022In recent years, the attention of the scientific world has focused on a clearance system of brain waste metabolites, called the glymphatic system, based on its... (Review)
Review
BACKGROUND
In recent years, the attention of the scientific world has focused on a clearance system of brain waste metabolites, called the glymphatic system, based on its similarity to the lymphatic system in peripheral tissue and the relevant role of the AQP4 glial channels and described for the first time in 2012. Consequently, numerous studies focused on its role in organ damage in cases of neuropathologies, including TBI.
METHODS
To evaluate the role that the glymphatic system has in the pathogenesis of TBI, on 23 March 2022, a systematic review of the literature according to PRISMA guidelines was carried out using the SCOPUS and Medline (via PubMed) databases, resulting in 12 articles after the selection process.
DISCUSSION AND CONCLUSION
The present review demonstrated that an alteration of AQP4 is associated with the accumulation of substances S100b, GFAP, and NSE, known markers of TBI in the forensic field. In addition, the alteration of the functionality of AQP4 favors edema, which, as already described, constitutes alterations of secondary brain injuries. Moreover, specific areas of the brain were demonstrated to be prone to alterations of the glymphatic pathway, suggesting their involvement in post-TBI damage. Therefore, further studies are mandatory. In this regard, a study protocol on cadavers is also proposed, based on the analyzed evidence.
Topics: Brain; Brain Injuries; Glymphatic System; Humans; Lymphatic System; Neuroglia
PubMed: 36012401
DOI: 10.3390/ijms23169138 -
The role of matrix metalloproteinase-9 and its inhibitor TIMP-1 in burn injury: a systematic review.International Journal of Burns and... 2021Matrix metalloproteinase-9 (MMP-9) and its endogenous inhibitor, tissue inhibitor of metalloproteinase-1 (TIMP-1), are key mediators of acute inflammation and regulators... (Review)
Review
Matrix metalloproteinase-9 (MMP-9) and its endogenous inhibitor, tissue inhibitor of metalloproteinase-1 (TIMP-1), are key mediators of acute inflammation and regulators of the wound healing process. The aim of this systematic review was to determine the local and systemic involvement of the MMP-9/TIMP-1 system following burn injury. Two databases (Scopus and MEDLINE) were searched for all studies reporting MMP-9 and/or TIMP-1 after burn injury. Based on our eligibility criteria, we reviewed 24 studies involving 508 burns patients in 11 clinical studies and 367 animals in 13 preclinical studies. Local, systemic, and peripheral gene expression, protein levels and activity of MMP-9 and TIMP-1 were assessed. Increased MMP-9 was reported at the site of injury early after burn trauma in all studies, and remained elevated in non-healing wounds. Increased TIMP-1 expression in burn wounds occurred later than MMP-9, and was persistent in hypertrophic burn scars. Similar to local expression, systemic MMP-9 and TIMP-1 concentrations were significantly elevated after burn injury in response to upregulation of proinflammatory cytokines. While no association was found between systemic MMP-9 concentration and extent of injury or outcome, serum or plasma TIMP-1 showed good correlation with survival and burn severity. This review also found evidence of the MMP-9/TIMP-1 system contributing to secondary tissue damage distant from the burn site, including burn-associated musculoskeletal damage and acute lung injury. In addition, increased MMP-9 synthesis and activity in the brain after peripheral burn may lead to blood-brain barrier dysfunction and cerebral edema, a significant contributor to mortality. This systematic review provides an overview of the available evidence of the role of MMP-9 and TIMP-1 in burn injury pathophysiology and finds that TIMP-1 may be a promising biomarker in outcome prognostication of burns patients. Large-scale studies of both pediatric and adult burns patients with increased female representation and repeated sampling are recommended to validate the reliability of TIMP-1 as a prognostic marker following burn injury.
PubMed: 34557330
DOI: No ID Found -
Indian Journal of Psychological Medicine 2016A number of atypical antipsychotics have been associated with peripheral edema. The exact cause is not known. We report two cases of olanzapine-induced edema and a brief... (Review)
Review
A number of atypical antipsychotics have been associated with peripheral edema. The exact cause is not known. We report two cases of olanzapine-induced edema and a brief review of atypical antipsychotic-induced edema, possible risk factors, etiology, and clinical features. The recommendation is given on different methods of managing this side effect.
PubMed: 27335511
DOI: 10.4103/0253-7176.183089 -
International Ophthalmology Jan 2022The pandemic of COVID-19 has been caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. Apart from respiratory malfunction, COVID-19 causes a... (Review)
Review
INTRODUCTION
The pandemic of COVID-19 has been caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. Apart from respiratory malfunction, COVID-19 causes a system-wide thromboembolic state, leading to serious cardiovascular, cerebrovascular and peripheral vascular manifestations. However, our knowledge regarding retinal manifestations due to systemic COVID-19 is minimal. This systematic review has comprehensively summarized all retinal manifestations secondary to COVID-19 disease recorded till date since the beginning of the pandemic.
METHODS
All studies published till November 27, 2020, which have reported retinal manifestations in COVID-19 patients were systematically reviewed using the PRISMA statement.
RESULTS
We included 15 articles: 11 case reports and four cross-sectional case series. The most commonly reported manifestations which did not affect visual acuity were retinal hemorrhages and cotton wool spots. The most common vision threatening manifestation was retinal vein occlusion with associated macular edema. Rarely, patients may also present with retinal arterial occlusions and ocular inflammation. These manifestations may occur from as soon as within a week after the onset of COVID-19 symptoms to more than 6 weeks after.
CONCLUSION
Mostly causing milder disease, COVID-19 may however lead to severe life-threatening thromboembolic complications, and systemic antithrombotic therapy has been suggested as a prophylactic and therapeutic management strategy for patients affected with serious systemic disease. However, both sick and apparently healthy patients may suffer from various retinal complications which may lead to loss of vision as well. No consensus regarding management of retinal complications with anticoagulants or anti-inflammatory medications have been proposed; however, they may be tackled on individual basis.
Topics: COVID-19; Cross-Sectional Studies; Humans; Pandemics; Retina; SARS-CoV-2
PubMed: 34379290
DOI: 10.1007/s10792-021-01996-7 -
Medicine Sep 2022To elucidate the relationship between peripheral edema and programmed cell death-1/programmed cell death ligand 1 (PD-1/PD-L1) inhibitors, the meta-analysis was... (Meta-Analysis)
Meta-Analysis
PURPOSE
To elucidate the relationship between peripheral edema and programmed cell death-1/programmed cell death ligand 1 (PD-1/PD-L1) inhibitors, the meta-analysis was performed.
METHOD
Following the guidelines of Preferred Reporting Items for Systematic Reviews and Meta-analyses, all-grade and grade 3-5 of peripheral edema data extracted from clinical trials were taken into account for the final comprehensive assessments.
RESULTS
Twenty-seven PD-1/PD-L1-related clinical trials with peripheral edema data were collected. Compared with chemotherapy (PD-1/PD-L1 vs chemotherapy), the risk of developing peripheral edema for all-grade was much lower (odds ratio [OR] = 0.36, 95% confidence interval [CI]: [0.23, 0.56], Z = 4.55 [P < .00001]). When PD-1/PD-L1 plus chemotherapy were compared with chemotherapy, no significant analysis results for all-grade was found (OR = 1.15, 95% CI:[0.93, 1.44], I2 = 25%, Z = 1.27 [P = .20]). Similar risk trends could also be found when the incidence risk of peripheral edema for grade 3-5 was evaluated. No obvious publication bias was identified throughout the total analysis process.
CONCLUSION
The effect of PD-1/PD-L1 inhibitor on the risk of developing peripheral edema was weaker than that of chemotherapy, and the combination with chemotherapy slightly increased the incidence risk of developing peripheral edema without statistical significance.
Topics: B7-H1 Antigen; Edema; Humans; Immune Checkpoint Inhibitors; Incidence; Neoplasms; Programmed Cell Death 1 Receptor
PubMed: 36086680
DOI: 10.1097/MD.0000000000030151 -
The Cochrane Database of Systematic... Mar 2023Acute primary angle closure (APAC) is a potentially blinding condition. It is one of the few ophthalmic emergencies and carries high rates of visual morbidity in the... (Review)
Review
BACKGROUND
Acute primary angle closure (APAC) is a potentially blinding condition. It is one of the few ophthalmic emergencies and carries high rates of visual morbidity in the absence of timely intervention. Laser peripheral iridotomy (LPI) has been the standard of care thus far. However, LPI does not eliminate the long-term risk of chronic angle closure glaucoma and other associated sequelae. There has been increasing interest in lens extraction as the primary treatment for the spectrum of primary angle closure disease, and it is as yet unclear whether these results can be extrapolated to APAC, and whether lens extraction provides better long-term outcomes. We therefore sought to evaluate the effectiveness of lens extraction in APAC to help inform the decision-making process. OBJECTIVES: To assess the effect of lens extraction compared to LPI in the treatment of APAC.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Trials Register) (2022, Issue 1), Ovid MEDLINE, Ovid MEDLINE E-pub Ahead of Print, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily (January 1946 to 10 January 2022), Embase (January 1947 to 10 January 2022), PubMed (1946 to 10 January 2022), Latin American and Caribbean Health Sciences Literature Database (LILACS) (1982 to 10 January 2022), ClinicalTrials.gov, and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP). We did not use any date or language restrictions in the electronic search. We last searched the electronic databases on 10 January 2022.
SELECTION CRITERIA
We included randomized controlled clinical trials comparing lens extraction against LPI in adult participants ( ≥ 35 years) with APAC in one or both eyes.
DATA COLLECTION AND ANALYSIS
We used standard Cochrane methodology and assessed the certainty of the body of evidence for prespecified outcomes using the GRADE approach.
MAIN RESULTS
We included two studies conducted in Hong Kong and Singapore, comprising 99 eyes (99 participants) of predominantly Chinese origin. The two studies compared LPI with phacoemulsification performed by experienced surgeons. We assessed that both studies were at high risk of bias. There were no studies evaluating other types of lens extraction procedures. Phacoemulsification may result in an increased proportion of participants with intraocular pressure (IOP) control compared with LPI at 18 to 24 months (risk ratio (RR) 1.66, 95% confidence interval (CI) 1.28 to 2.15; 2 studies, n = 97; low certainty evidence) and may reduce the need for further IOP-lowering surgery within 24 months (RR 0.07, 96% CI 0.01 to 0.51; 2 studies, n = 99; very low certainty evidence). Phacoemulsification may result in a lower mean IOP at 12 months compared to LPI (mean difference (MD) -3.20, 95% CI -4.79 to -1.61; 1 study, n = 62; low certainty evidence) and a slightly lower mean number of IOP-lowering medications at 18 months (MD -0.87, 95% CI -1.28 to -0.46; 1 study, n = 60; low certainty evidence), but this may not be clinically significant. Phacoemulsification may have little to no effect on the proportion of participants with one or more recurrent APAC episodes in the same eye (RR 0.32, 95% CI 0.01 to 7.30; 1 study, n = 37; very low certainty evidence). Phacoemulsification may result in a wider iridocorneal angle assessed by Shaffer grading at six months (MD 1.15, 95% CI 0.83 to 1.47; 1 study, n = 62; very low certainty evidence). Phacoemulsification may have little to no effect on logMAR best-corrected visual acuity (BCVA) at six months (MD -0.09, 95% CI -0.20 to 0.02; 2 studies, n = 94; very low certainty evidence). There was no evidence of a difference in the extent of peripheral anterior synechiae (PAS) (clock hours) between intervention arms at 6 months (MD -1.86, 95% CI -7.03 to 3.32; 2 studies, n = 94; very low certainty evidence), although the phacoemulsification group may have less PAS (degrees) at 12 months (MD -94.20, 95% CI -140.37 to -48.03; 1 study, n = 62) and 18 months (MD -127.30, 95% CI -168.91 to -85.69; 1 study, n = 60). In one study, there were 26 adverse events in the phacoemulsification group: intraoperative corneal edema (n = 12), posterior capsular rupture (n = 1), intraoperative bleeding from iris root (n = 1), postoperative fibrinous anterior chamber reaction (n = 7), and visually significant posterior capsular opacification (n = 5), and no cases of suprachoroidal hemorrhage or endophthalmitis. There were four adverse events in the LPI group: closed iridotomy (n = 1) and small iridotomies that required supplementary laser (n = 3). In the other study, there was one adverse event in the phacoemulsification group (IOP > 30 mmHg on day 1 postoperatively (n = 1)), and no intraoperative complications. There were five adverse events in the LPI group: transient hemorrhage (n = 1), corneal burn (n = 1), and repeated LPI because of non-patency (n = 3). Neither study reported health- or vision-related quality of life measures.
AUTHORS' CONCLUSIONS
Low certainty evidence suggests that early lens extraction may produce more favorable outcomes compared to initial LPI in terms of IOP control. Evidence for other outcomes is less clear. Future high-quality and longer-term studies evaluating the effects of either intervention on the development of glaucomatous damage and visual field changes as well as health-related quality of life measures would be helpful.
Topics: Adult; Humans; Cataract Extraction; Glaucoma; Intraocular Pressure; Phacoemulsification; Quality of Life
PubMed: 36884304
DOI: 10.1002/14651858.CD015116.pub2 -
Frontiers in Neuroscience 2021Peripheral neuropathy can be caused by diabetes mellitus and HIV infection, and often leaves patients with treatment-resistant neuropathic pain. To better treat this...
Peripheral neuropathy can be caused by diabetes mellitus and HIV infection, and often leaves patients with treatment-resistant neuropathic pain. To better treat this condition, we need greater understanding of the pathogenesis, as well as objective biomarkers to predict treatment response. Magnetic resonance imaging (MRI) has a firm place as a biomarker for diseases of the central nervous system (CNS), but until recently has had little role for disease of the peripheral nervous system. To review the current state-of-the-art of peripheral nerve MRI in diabetic and HIV symmetrical polyneuropathy. We used systematic literature search methods to identify all studies currently published, using this as a basis for a narrative review to discuss major findings in the literature. We also assessed risk of bias, as well as technical aspects of MRI and statistical analysis. Protocol was pre-registered on NIHR PROSPERO database. MEDLINE, Web of Science and EMBASE databases were searched from 1946 to 15th August 2020 for all studies investigating either diabetic or HIV neuropathy and MRI, focusing exclusively on studies investigating symmetrical polyneuropathy. The NIH quality assessment tool for observational and cross-sectional cohort studies was used for risk of bias assessment. The search resulted in 18 papers eligible for review, 18 for diabetic neuropathy and 0 for HIV neuropathy. Risk of bias assessment demonstrated that studies generally lacked explicit sample size justifications, and some may be underpowered. Whilst most studies made efforts to balance groups for confounding variables (age, gender, BMI, disease duration), there was lack of consistency between studies. Overall, the literature provides convincing evidence that DPN is associated with larger nerve cross sectional area, T2-weighted hyperintense and hypointense lesions, evidence of nerve oedema on Dixon imaging, decreased fractional anisotropy and increased apparent diffusion coefficient compared with controls. Analysis to date is largely restricted to the sciatic nerve or its branches. There is emerging evidence that various structural MR metrics may be useful as biomarkers in diabetic polyneuropathy, and areas for future direction are discussed. Expanding this technique to other forms of peripheral neuropathy, including HIV neuropathy, would be of value. (identifier: CRD 42020167322) https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=167322.
PubMed: 34621152
DOI: 10.3389/fnins.2021.727311 -
European Heart Journal Open Mar 2023People living with cardiac sarcoidosis (CS) are likely to have worse clinical outcomes and greater impairment on health-related quality of life (HRQoL) than other... (Review)
Review
People living with cardiac sarcoidosis (CS) are likely to have worse clinical outcomes and greater impairment on health-related quality of life (HRQoL) than other sarcoidosis manifestations. CS can result in a constellation of intrusive symptoms (such as palpitations, dizziness, syncope/pre-syncope, chest pain, dyspnoea, orthopnoea, or peripheral oedema) and/or life-threatening episodes, requiring consideration of invasive cardiac procedures for diagnosis and for the management of acute events. Additionally, the presence of multisystemic involvement and persistent non-specific sarcoidosis symptoms negatively affect HRQoL. A systematic review was undertaken to explore the impact of CS on HRQoL in adults with CS. Multiple bibliographic databases were searched for studies with HRQoL as primary or secondary outcomes in CS (PROSPERO registration: CRD42019119752). Data extraction and quality assessments were undertaken independently by two authors. From the initial 1609 identified records, only 11 studies included CS patients but none specifically reported HRQoL scores for CS patients. The average representation of CS patients was 14.5% within these cohorts (range 2-22%). The majority (73%) was conducted in single-centre tertiary care settings, and only one study (9%) included longitudinal HRQoL data. CS patients were among those sarcoidosis patients with impaired HRQoL and worse outcomes, requiring higher doses of sarcoidosis-specific therapy which contribute to further deterioration of HRQoL. Sarcoidosis studies do not incorporate stratified HRQoL scores for CS patients. While there is a need for longitudinal and multicentre studies assessing HRQoL outcomes in CS cohorts, the development of CS-specific tools is also needed.
PubMed: 36974155
DOI: 10.1093/ehjopen/oead009 -
Journal of Foot and Ankle Research Sep 2023Lower limb oedema is a common co-morbidity in those with diabetes and foot ulceration and is linked with increased amputation risk. There is no current guidance for the... (Review)
Review
BACKGROUND
Lower limb oedema is a common co-morbidity in those with diabetes and foot ulceration and is linked with increased amputation risk. There is no current guidance for the treatment of concurrent diabetic foot ulcers and lower limb oedema, leading to uncertainty around the safety and efficacy of combination approaches incorporating offloading and compression therapies. To determine indications and contraindications for such strategies and identify any other supplementary treatment approaches, a scoping review was undertaken to map the evidence relating to off-loading and compression therapy strategies to treat both diabetic foot ulcers and lower limb oedema in combination.
METHODS
Following the Joanna Briggs Institute (JBI) and PRISMA - Scoping Review (ScR) guidance, this review included published and unpublished literature from inception to April 2022. Literature was sourced using electronic databases including Cochrane Library, PubMed, CINAHL, AMED; websites; professional journals and reference lists of included literature. Eligible literature discussed the management of both diabetic foot ulceration and lower limb oedema and included at least one of the treatment strategies of interest. Data extraction involved recording any suggested off-loading, compression therapy or supplementary treatment strategies and any suggested indications, contraindications and cautions for their use.
RESULTS
Five hundred twenty-two publications were found relating to the management of diabetic foot ulcers with an off-loading strategy or the management of lower limb oedema with compression therapy. 51 publications were eligible for inclusion in the review. The majority of the excluded publications did not discuss the situation where diabetic foot ulceration and lower limb oedema present concurrently.
CONCLUSIONS
Most literature, focused on oedema management with compression therapy to conclude that compression therapy should be avoided in the presence of severe peripheral arterial disease. Less literature was found regarding off-loading strategies, but it was recommended that knee-high devices should be used with caution when off-loading diabetic foot ulcers in those with lower limb oedema. Treatment options to manage both conditions concurrently was identified as a research gap. Integrated working between specialist healthcare teams, was the supplementary strategy most frequently recommended. In the absence of a definitive treatment solution, clinicians are encouraged to use clinical reasoning along with support from specialist peers to establish the best, individualised treatment approach for their patients.
TRIAL REGISTRATION
Open Science Framework (osf.io/crb78).
Topics: Humans; Diabetic Foot; Amputation, Surgical; Databases, Factual; Edema; Evidence Gaps; Diabetes Mellitus
PubMed: 37674176
DOI: 10.1186/s13047-023-00659-3