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Clinical Reviews in Allergy & Immunology Jun 2018Non-hereditary angioedema (AE) with normal C1 esterase inhibitor (C1INH) can be presumably bradykinin- or mast cell-mediated, or of unknown cause. In this systematic... (Review)
Review
Non-hereditary angioedema (AE) with normal C1 esterase inhibitor (C1INH) can be presumably bradykinin- or mast cell-mediated, or of unknown cause. In this systematic review, we searched PubMed, EMBASE, and Scopus to provide an overview of the efficacy of different treatment options for the abovementioned subtypes of refractory non-hereditary AE with or without wheals and with normal C1INH. After study selection and risk of bias assessment, 61 articles were included for data extraction and analysis. Therapies were described for angiotensin-converting enzyme inhibitor-induced AE (ACEi-AE), for idiopathic AE, and for AE with wheals. Described treatments consisted of ecallantide, icatibant, C1INH, fresh frozen plasma (FFP), tranexamic acid (TA), and omalizumab. Additionally, individual studies for anti-vitamin K, progestin, and methotrexate were found. Safety information was available in 26 articles. Most therapies were used off-label and in few patients. There is a need for additional studies with a high level of evidence. In conclusion, in acute attacks of ACEi-AE and idiopathic AE, treatment with icatibant, C1INH, TA, and FFP often leads to symptom relief within 2 h, with limited side effects. For prophylactic treatment of idiopathic AE and AE with wheals, omalizumab, TA, and C1INH were effective and safe in the majority of patients.
Topics: Angioedema; Angiotensin-Converting Enzyme Inhibitors; Bradykinin; Humans; Omalizumab; Progestins; Tranexamic Acid; Treatment Outcome
PubMed: 27672078
DOI: 10.1007/s12016-016-8585-0 -
International Braz J Urol : Official... 2023COVID-19 continues to be an urgent World issue. Receptors of angiotensin converting enzyme 2 (ACE2), gateway of SARS-CoV-2, are present in the lungs, bladder, prostate,... (Review)
Review
PURPOSE
COVID-19 continues to be an urgent World issue. Receptors of angiotensin converting enzyme 2 (ACE2), gateway of SARS-CoV-2, are present in the lungs, bladder, prostate, and testicles. Therefore, these organs face high risk of damage caused by the virus and this mechanism may explain non-respiratory symptoms of the disease.
MATERIALS AND METHODS
This systematic review, guided by the PRIMSA statement, was proposed to elucidate possible urological complications of COVID-19. Searches were carried out in Medline (PubMed), Cochrane (CENTRAL), Embase, MedRxiv and LILACS. Bias analysis was made using the specific Newcastle-Ottawa Scale for each study design.
RESULTS
Search was carried out until April 2022, and 8,477 articles were identified. Forty-nine of them were included in this systematic review. There is evidence that lower urinary tract symptoms and acute scrotum may be signs of COVID-19 in men, although in a small proportion. Also, the disease may have a transitory impact on male fertility, evidenced by several alterations in sperm counts. However, it must be clarified whether this impact is transitory, or may last for longer periods. Several patients showed reduction of total value of testosterone. Two authors linked low levels of testosterone with worse outcomes of COVID-19, suggesting that the hormone may be used as an early biomarker of the severity of the disease. Moreover, it is extremely unlikely that SARS-CoV-2 is transmitted by semen.
CONCLUSION
This systematic review identified possible repercussions of COVID-19 in the urinary as well as in the male reproductive system.
Topics: Male; Humans; COVID-19; SARS-CoV-2; Semen; Testosterone
PubMed: 36512453
DOI: 10.1590/S1677-5538.IBJU.2022.0281 -
Molecular Biology Reports Nov 2022Angiotensin-converting enzyme 2 (ACE2) is known as the major viral entry site for SARS-CoV-2. However, viral tissue tropism and high rate of infectivity do not directly... (Review)
Review
BACKGROUND
Angiotensin-converting enzyme 2 (ACE2) is known as the major viral entry site for SARS-CoV-2. However, viral tissue tropism and high rate of infectivity do not directly correspond with the level of ACE2 expression in the organs. It may suggest involvement of other receptors or accessory membrane proteins in SARSCoV-2 cell entry.
METHODS AND RESULTS
A systematic search was carried out in PubMed/Medline, EMBASE, and Cochrane Library for studies reporting SARS-CoV-2 cell entry. We used a group of the MeSH terms including "cell entry", "surface receptor", "ACE2", and "SARS-CoV-2". We reviewed all selected papers published in English up to end of February 2022. We found several receptors or auxiliary membrane proteins (including CD147, NRP-1, CD26, AGTR2, Band3, KREMEN1, ASGR1, ANP, TMEM30A, CLEC4G, and LDLRAD3) along with ACE2 that facilitate virus entry and transmission. Expression of Band3 protein on the surface of erythrocytes and evidence of binding with S protein of SARS-CoV-2 may explain asymptomatic hypoxemia during COVID19 infection. The variants of SARS-CoV-2 including the B.1.1.7 (Alpha), B.1.617.1 (Kappa), B.1.617.2 (Delta), B.1.617.2+ (Delta+), and B.1.1.529 (Omicron) may have different potency to bond with these receptors.
CONCLUSIONS
The high rate of infectivity of SARS-CoV-2 may be due to its ability to enter the host cell through a group of cell surface receptors. These receptors are potential targets to develop novel therapeutic agents for SARS-CoV-2.
Topics: Humans; Angiotensin-Converting Enzyme 2; Asialoglycoprotein Receptor; COVID-19; Protein Binding; Receptors, Virus; SARS-CoV-2; Spike Glycoprotein, Coronavirus
PubMed: 35754059
DOI: 10.1007/s11033-022-07700-x -
Frontiers in Immunology 2023The incidence and risk factors of acute kidney injury (AKI) in patients with malignancies receiving immune checkpoint inhibitors (ICIs) are being extensively reported... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The incidence and risk factors of acute kidney injury (AKI) in patients with malignancies receiving immune checkpoint inhibitors (ICIs) are being extensively reported with their widespread application.
OBJECTIVE
This study aimed to quantify the incidence and identify risk factors of AKI in cancer patients treated with ICIs.
METHODS
We searched the electronic databases of PubMed/Medline, Web of Science, Cochrane and Embase before 1 February 2023 on the incidence and risk factors of AKI in patients receiving ICIs and registered the protocol in PROSPERO (CRD42023391939). A random-effect meta-analysis was performed to quantify the pooled incidence estimate of AKI, identify risk factors with pooled odds ratios (ORs) and 95% confidence intervals (95% CIs) and investigate the median latency period of ICI-AKI in patients treated with ICIs. Assessment of study quality, meta-regression, and sensitivity and publication bias analyses were conducted.
RESULTS
In total, 27 studies consisting of 24048 participants were included in this systematic review and meta-analysis. The overall pooled incidence of AKI secondary to ICIs was 5.7% (95% CI: 3.7%-8.2%). Significant risk factors were older age (OR: 1.01, 95% CI: 1.00-1.03), preexisting chronic kidney disease (CKD) (OR: 2.90, 95% CI: 1.65-5.11), ipilimumab (OR: 2.66, 95% CI: 1.42-4.98), combination of ICIs (OR: 2.45, 95% CI: 1.40-4.31), extrarenal immune-related adverse events (irAEs) (OR: 2.34, 95% CI: 1.53-3.59), and proton pump inhibitor (PPI) (OR: 2.23, 95% CI: 1.88-2.64), nonsteroidal anti-inflammatory drug (NSAID) (OR: 2.61, 95% CI: 1.90-3.57), fluindione (OR: 6.48, 95% CI: 2.72-15.46), diuretic (OR: 1.78, 95% CI: 1.32-2.40) and angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin-receptor blockers (ARBs) (pooled OR: 1.76, 95% CI: 1.15-2.68) use. Median time from ICIs initiation to AKI was 108.07 days. Sensitivity and publication bias analyses indicated robust results for this study.
CONCLUSION
The occurrence of AKI following ICIs was not uncommon, with an incidence of 5.7% and a median time interval of 108.07 days after ICIs initiation. Older age, preexisting chronic kidney disease (CKD), ipilimumab, combined use of ICIs, extrarenal irAEs, and PPI, NSAID, fluindione, diuretics and ACEI/ARB use are risk factors for AKI in patients receiving ICIs.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/, identifier CRD42023391939.
Topics: Humans; Immune Checkpoint Inhibitors; Ipilimumab; Angiotensin Receptor Antagonists; Incidence; Angiotensin-Converting Enzyme Inhibitors; Neoplasms; Acute Kidney Injury; Anti-Inflammatory Agents, Non-Steroidal
PubMed: 37313406
DOI: 10.3389/fimmu.2023.1173952 -
Nephrology, Dialysis, Transplantation :... Oct 2023Dual renin-angiotensin-aldosterone system (RAAS) blockade involves dual therapy with a combination of angiotensin-converting enzyme inhibitors (ACEis),... (Meta-Analysis)
Meta-Analysis
The association between dual RAAS inhibition and risk of acute kidney injury and hyperkalemia in patients with diabetic kidney disease: a systematic review and meta-analysis.
BACKGROUND AND OBJECTIVES
Dual renin-angiotensin-aldosterone system (RAAS) blockade involves dual therapy with a combination of angiotensin-converting enzyme inhibitors (ACEis), angiotensin-receptor blockers (ARBs), direct renin inhibitors (DRIs), or mineralocorticoid receptor antagonists (MRAs). It is hypothesized that dual RAAS blockade would result in a more complete inhibition of the RAAS cascade. However, large clinical trials on dual RAAS inhibition have shown increased risk of acute kidney injury (AKI) and hyperkalemia without additional benefit on mortality, cardiovascular events, or chronic kidney disease (CKD) progression compared to RAAS inhibitor monotherapy in patients with diabetic kidney disease (DKD). The development of newer, more selective non-steroidal MRAs as cardiorenal protective therapies has created a new opportunity for dual RAAS inhibition. We conducted a systematic review and meta-analysis of the risks of AKI and hyperkalemia with dual RAAS blockade in patients with DKD.
DESIGN, SETTING, PARTICIPANTS, AND MEASUREMENTS
This is a systematic review and meta-analysis of the randomized controlled trials (RCT) published from 1 January 2006 to 30 May 2022. The study population included adult patients with DKD receiving dual RAAS blockade. A total of 31 RCTs and 33 048 patients were included in the systematic review. Pooled risk ratios (RRs) and 95% confidence intervals (CIs) were calculated using random effects.
RESULTS
There were 208 AKI events in 2690 patients on ACEi + ARB versus 170 in 4264 patients with ACEi or ARB monotherapy (pooled RR 1.48, 95% CI: 1.23-1.39). There were 304 hyperkalemia events in 2818 patients on ACEi + ARB versus 208 in 4396 patients with ACEi or ARB monotherapy (pooled RR 1.97, 95% CI: 1.32-2.94). A non-steroidal MRA + ACEi or ARB showed no increase in the risk of AKI (pooled RR 0.97, 95% CI: 0.81-1.16) compared to ACEi or ARB monotherapy but had a 2-fold higher risk of hyperkalemia with 953 events in 7837 patients in dual therapy versus 454 events in 6895 patients in monotherapy (pooled RR 2.05, 95% CI: 1.84-2.28). A steroidal MRA + ACEi or ARB had a 5-fold higher risk of hyperkalemia with 28 events in 245 at risk in dual therapy versus five events in 248 at risk in monotherapy (pooled RR 5.42 95% CI: 2.15-13.67).
CONCLUSION
Dual therapy with RAASi is associated with an increased risk of AKI and hyperkalemia compared to RAASi monotherapy. Conversely, dual therapy with RAAS inhibitors and non-steroidal MRAs have no additional risk of AKI but a similar risk of hyperkalemia, which is lower than dual therapy with RAAS inhibitors and steroidal MRAs.
Topics: Adult; Humans; Renin-Angiotensin System; Diabetic Nephropathies; Hyperkalemia; Angiotensin-Converting Enzyme Inhibitors; Angiotensin Receptor Antagonists; Acute Kidney Injury; Diabetes Mellitus
PubMed: 37309038
DOI: 10.1093/ndt/gfad101 -
American Journal of Ophthalmology Nov 2023We synthesized the literature on the association between systemic antihypertensive medications with intraocular pressure (IOP) and glaucoma. Antihypertensive medications... (Review)
Review
PURPOSE
We synthesized the literature on the association between systemic antihypertensive medications with intraocular pressure (IOP) and glaucoma. Antihypertensive medications included β-blockers, calcium channel blockers, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and diuretics.
DESIGN
Systematic review and meta-analysis.
METHODS
Databases were searched for relevant articles until December 5, 2022. Studies were eligible if they examined (1) the association between systemic antihypertensive medications with glaucoma or (2) the association between systemic antihypertensive medications with IOP in those without glaucoma or ocular hypertension. The protocol was registered at PROSPERO (International Prospective Register of Systematic Reviews; registration ID: CRD42022352028).
RESULTS
A total of 11 studies were included in the review and 10 studies in the meta-analysis. The 3 studies on IOP were cross-sectional, whereas the 8 studies on glaucoma were primarily longitudinal. In the meta-analysis, β-blockers were associated with a lower odds of glaucoma (odds ratio: 0.83, 95% CI: 0.75-0.92, 7 studies, n = 219,535) and lower IOP (β: -0.53, 95% CI: -1.05 to -0.02, 3 studies, n = 28,683). Calcium channel blockers were associated with a higher odds of glaucoma (odds ratio: 1.13, 95% CI: 1.03-1.24, 7 studies, n = 219,535) but not with IOP (β: -0.11, 95% CI: -0.25 to 0.03, 2 studies, n = 20,620). There were no consistent associations between angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, or diuretics with glaucoma or IOP.
CONCLUSIONS
Systemic antihypertensive medications have heterogeneous effects on glaucoma and IOP. Clinicians should be aware that systemic antihypertensive medications may mask elevated IOP or positively or negatively affect the risk of glaucoma.
PubMed: 36966883
DOI: 10.1016/j.ajo.2023.03.014 -
British Journal of Cancer Jan 2023The association between the use of angiotensin-converting enzyme inhibitors (ACEIs) and lung cancer risk remains controversial. This study evaluated the association... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The association between the use of angiotensin-converting enzyme inhibitors (ACEIs) and lung cancer risk remains controversial. This study evaluated the association between the use of ACEIs and lung cancer risk.
METHODS
Records from five databases were searched from inception to 26 January 2022. Clinical studies involving persons aged ≥18 years with at least one year of follow-up and reporting adverse events, including lung cancer, were recorded with separate outcome reports supplied for the ACEIs and control groups. Data were extracted independently by three authors and pooled using a random-effects model. The primary outcome was lung cancer development. Odds ratios (ORs) with 95% confidence intervals (CIs) and lung cancer-related morbidity were calculated.
RESULTS
Of 2400 records screened, 13,061,226 patients were included from seven cohort studies and four case-control studies. Pooled results showed that ACEIs use was linked to increased lung cancer risk (OR 1.19, 95% CI 1.05-1.36; P = 0.008), with high heterogeneity (I = 98%).
CONCLUSIONS
ACEI usage is a greater risk factor for lung carcinogenesis than angiotensin receptor blocker use, especially in Asian patients. Further randomised controlled trials are needed to confirm the causal association between the use of ACEIs and lung cancer risk.
Topics: Humans; Adolescent; Adult; Angiotensin-Converting Enzyme Inhibitors; Angiotensin Receptor Antagonists; Risk Factors; Lung Neoplasms; Case-Control Studies
PubMed: 36396817
DOI: 10.1038/s41416-022-02029-5 -
Cureus Jan 2023The objective of this systematic review was to investigate the expression of angiotensin converting enzyme 2 (ACE 2) in the head and neck region. We examined the... (Review)
Review
The objective of this systematic review was to investigate the expression of angiotensin converting enzyme 2 (ACE 2) in the head and neck region. We examined the evidence of the association of ACE 2 expression in oral tissues, salivary glands, and head and neck carcinoma. We searched Pub Med/Medline, Biorxiv, and Google Scholar to identify relevant literature. Studies reporting ACE 2 expression in human oral tissues and with a focus on head and neck carcinoma samples were included. From 110 studies, we extracted 15 studies analyzing the distribution and expression of ACE 2 in different head and neck tissues - olfactory mucosa and nasopharynx n=5, oral mucosa n=5, salivary gland n=5, head and neck squamous cell carcinoma patients n=3. ACE 2 was found to be expressed at a 4.43-fold increase in the head and neck region (OR, 4.43; 95% CI, 3.76-5.22; I= 97%, P=<0.00001) when compared with controls (other tissues except for head and neck region). RNA expression of ACE 2 was 60% higher in head and neck squamous cell carcinoma patients than that in the normal tissues (OR=0.60, 95% CI, 0.04-9.26, P=0.00001). In conclusion, the meta-analysis of the studies indicated that ACE 2 is highly expressed in olfactory mucosa, nasopharynx, oral mucosa, and salivary glands. Furthermore, the results indicate that ACE 2 expression is increased in patients with head and neck cancer.
PubMed: 36819393
DOI: 10.7759/cureus.33673 -
International Journal of Molecular... Mar 2022Stroke is the primary cause of disability in the adult population. Hypertension represents the leading risk factor being present in almost half the patients. The... (Review)
Review
Stroke is the primary cause of disability in the adult population. Hypertension represents the leading risk factor being present in almost half the patients. The renin-angiotensin system is involved in the physiopathology of stroke and has an essential impact on hypertension as a risk factor. This article targeted the role of the renin-angiotensin system in stroke neuroprotection by reviewing the current literature available. The mechanism of action of the renin-angiotensin system was observed through the effects on AT1, AT2, and Mas receptors. The neuroprotective properties ascertained by angiotensin in stroke seem to be independent of the blood pressure reduction mechanism, and include neuroregeneration, angiogenesis, and increased neuronal resistance to hypoxia. The future relationship of stroke and the renin-angiotensin system is full of possibilities, as new agonist molecules emerge as potential candidates to restrict the impairment caused by stroke.
Topics: Humans; Hypertension; Neuroprotection; Renin-Angiotensin System; Stroke
PubMed: 35409237
DOI: 10.3390/ijms23073876 -
Arquivos Brasileiros de Cardiologia 2023The evidence supporting the use of renin-angiotensin-aldosterone system (RAAS) inhibitors and beta-blockers for the prevention of anthracycline-induced cardiomyopathy is... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The evidence supporting the use of renin-angiotensin-aldosterone system (RAAS) inhibitors and beta-blockers for the prevention of anthracycline-induced cardiomyopathy is controversial.
OBJECTIVE
We performed a meta-analysis to assess the effectiveness of these drugs in preventing cardiotoxicity.
METHODS
The meta-analysis included prospective, randomized studies in adults receiving anthracycline chemotherapy and compared the use of RAAS inhibitors or beta-blockers versus placebo with a follow-up of 6 to 18 months. The primary outcome was change in left ventricular ejection fraction (LVEF) during chemotherapy. Secondary outcomes were the incidence of heart failure, all-cause mortality, and changes in end-diastolic measurement. Heterogeneity was assessed by stratification and meta-regression. A significance level of p < 0.05 was adopted.
RESULTS
The search resulted in 17 studies, totaling 1,530 patients. The variation (delta) in LVEF was evaluated in 14 studies. Neurohormonal therapy was associated with a lower delta in pre- versus post-therapy LVEF (weighted mean difference 4.42 [95% confidence interval 2.3 to 6.6]) and higher final LVEF (p < 0.001). Treatment resulted in a lower incidence of heart failure (risk ratio 0.45 [95% confidence interval 0.3 to 0.7]). There was no effect on mortality (p = 0.3). For analysis of LVEF, substantial heterogeneity was documented, which was not explained by the variables explored in the study.
CONCLUSION
The use of RAAS inhibitors and beta-blockers to prevent anthracycline-induced cardiotoxicity was associated with less pronounced reduction in LVEF, higher final LVEF, and lower incidence of heart failure. No changes in mortality were observed. (CRD PROSPERO 42019133615).
Topics: Adult; Humans; Renin-Angiotensin System; Stroke Volume; Cardiotoxicity; Ventricular Function, Left; Anthracyclines; Prospective Studies; Adrenergic beta-Antagonists; Antibiotics, Antineoplastic; Heart Failure
PubMed: 37255127
DOI: 10.36660/abc.20220298