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International Journal of Gynecological... Oct 2016At present, considerable efforts have been made to identify new cancer-specific markers for ovarian cancer (OC) diagnosis and the kallikrein-related peptidases (KLKs)... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
At present, considerable efforts have been made to identify new cancer-specific markers for ovarian cancer (OC) diagnosis and the kallikrein-related peptidases (KLKs) family is one of the most studied candidates. This meta-analysis aims to evaluate the pooled diagnostic value of serum KLK measurement for diagnosing OC.
METHODS
The Cochrane Library, PubMed, Excerpt Medica Database were searched for all relevant literature. The Quality Assessment for Studies of Diagnostic Accuracy tool was applied to assess the quality of enrolled studies. Statistical analysis was conducted by using Stata 13.0 software and Meta-Disc.
RESULTS
A total of 15 studies from 13 articles were considered eligible for inclusion in the present analysis. The following pooled parameters were calculated by using the bivariate model: sensitivity of 0.582 (95% confidence interval [CI], 0.517-0.644), specificity of 0.909 (95% CI, 0.833-0.952), positive likelihood ratios of 6.367 (95% CI, 3.330-12.172), negative likelihood ratios of 0.460 (95% CI, 0.388-0.546), diagnostic odds ratio of 13.831 (95% CI, 6.460-29.614), respectively.
CONCLUSIONS
Kallikrein-related peptidase seems to be a promising candidate biomarker in diagnosing OC, but the associated poor sensitivity of KLK individually may limit its value in clinical application. To resolve this problem, the combination of KLK and other markers may offer improved performance than a single marker.
Topics: Biomarkers, Tumor; Female; Humans; Ovarian Neoplasms; Plasma Kallikrein; Randomized Controlled Trials as Topic
PubMed: 27465901
DOI: 10.1097/IGC.0000000000000781 -
Laryngoscope Investigative... Jun 2021This study systematically reviews the existing literature on the management of hereditary angioedema (HAE) and provides an update on the clinical presentation and... (Review)
Review
OBJECTIVE
This study systematically reviews the existing literature on the management of hereditary angioedema (HAE) and provides an update on the clinical presentation and specific therapies.
METHODS
A literature search of PubMed and Embase databases was conducted from start of the database to February 2021. Inclusion criteria included relevant systematic reviews, randomized control clinical trials, prospective and retrospective cohort studies, and outcomes research published in English and available in full-text. Out of 310 candidate articles, a total of 55 articles were included in our study.
RESULTS
The most common genetic form of HAE in up to 85% of cases is caused by low levels of C1 esterase inhibitor (C1-INH) protein, leading to a bradykinin-mediated increase in vascular permeability. During an attack of HAE, abortive treatment with C1-INH replacement is most commonly described, however, icatibant, ecallantide, or fresh frozen plasma are also used. Long-term prophylaxis in the form of C1-INH replacement (subcutaneous or intravenous), monoclonal antibodies targeting plasma kallikrein, attenuated androgens, and transexemic acid should be considered for those who suffer from frequent, severe attacks.
CONCLUSION
Progressively distal involvement of the upper airway, especially the larynx, has been shown to pose an increased risk of asphyxiation and death in the acute presentation of HAE. Evaluation by an otolaryngologist is often sought during the emergent clinical management of HAE; therefore, it is prudent that the consulting physician is well-versed in the prompt recognition, triage of patients, and appropriate treatment modalities.
LEVEL OF EVIDENCE
1A.
PubMed: 34195359
DOI: 10.1002/lio2.555 -
Pharmacotherapy for Angiotensin-Converting Enzyme Inhibitor-Induced Angioedema: A Systematic Review.Otolaryngology--head and Neck Surgery :... Feb 2018Objective Angioedema is a potentially life-threatening complication of angiotensin-converting enzyme inhibitor (ACEI) use, occurring in up to 0.5% of users. Although the... (Review)
Review
Objective Angioedema is a potentially life-threatening complication of angiotensin-converting enzyme inhibitor (ACEI) use, occurring in up to 0.5% of users. Although the pathophysiology of ACEI-induced angioedema is attributable to elevated serum bradykinin, standard management typically includes corticosteroids and antihistamines. We sought to summarize the evidence supporting pharmacotherapy for ACEI-induced angioedema. Data Sources PubMed, MEDLINE, and Embase portals. Methods A systematic literature review was conducted according to the PRISMA guidelines. Databases were queried by 3 independent reviewers for English-language studies published between 1980 and 2017. The initial search screened for all occurrences of "angioedema" and then was further refined to include studies of ACEI-related cases and exclude hereditary angioedema. Results Five articles representing 218 cases were identified, including 3 randomized controlled trials and 2 prospective case series with historical controls. One of 2 studies of icatibant (bradykinin B2 receptor antagonist) found more rapid symptom improvement than that with a control group of corticosteroids and antihistamines. Two studies of ecallantide (plasma kallikrein inhibitor) and 1 study of C1 inhibitor replacement found no significant benefit over control. No studies were identified that compared the efficacy of corticosteroids with antihistamines, of one dose with another, of fresh frozen plasma, or of combination therapy. Conclusion The efficacy of treatment of ACEI-induced angioedema with bradykinin antagonists, kallikrein inhibitor, and C1 inhibitor warrants further study. Although consistent benefit of these medications has not been demonstrated, their use has not caused harm. One study examining off-label use of icatibant has demonstrated efficacy over control. In addition, further study is needed to establish the efficacy and mechanism of action of standard pharmacotherapy such as corticosteroids and antihistamines in treatment of this condition.
Topics: Adrenal Cortex Hormones; Angioedema; Angiotensin-Converting Enzyme Inhibitors; Bradykinin B2 Receptor Antagonists; Histamine Antagonists; Humans
PubMed: 29112487
DOI: 10.1177/0194599817737974 -
The Cochrane Database of Systematic... 2000Oligo-astheno-teratospermia (sperm of low concentration, reduced motility and increased abnormal morphology) of unknown cause is common and the need for treatment is... (Review)
Review
BACKGROUND
Oligo-astheno-teratospermia (sperm of low concentration, reduced motility and increased abnormal morphology) of unknown cause is common and the need for treatment is felt by patients and doctors alike. As a result, a variety of empirical, non-specific treatments have been used in an attempt to improve semen characteristics and fertility. One suggested treatment for idiopathic oligo- and/or asthenospermia is the administration of kallikrein (kallidinogenase), a kinin-releasing enzyme (or kininogenase). The kinin biological system is complex and involves kininogen (the substrate), kininogenases (the activating enzymes), kinins (the effectors) and kininases (the inactivating enzymes). All four components of the kinin system have been found in the genitalia and in semen. Kallikrein releases 2 major kinins, kallidin and bradykinin, from seminal plasma kininogens. Activated kinins in semen affect sperm motility and metabolism. In vitro addition of kallikrein to semen has been shown to have a positive effect on sperm motility, sperm velocity, cervical mucus penetration, penetration of zona-free hamster eggs and post-thaw survival and motility rate after semen cryopreservation. The latter observation, however, was not confirmed in a more recent comparison of motility stimulants for cryopreserved semen using computerised sperm motion analysis. In vitro treatment of semen with kallikrein has been employed in a clinical context during sperm preparation prior to insemination. Although the kinin system may also be involved in the regulation of spermatogenesis in vivo, a clear mechanism of action is missing. Multiple suggestions on how an increase in kinin levels in the genital tract influences spermatogenesis at the testicular levels have been made by various authors.
OBJECTIVES
To determine whether treatment of the male with drugs enhancing kinin levles increases pregnancy rates among couples where failure to conceive has been attributed to idiopathic oligo- and/or asthenospermia. Effects on sperm parameters and sex hormones were studied as secondary outcomes.
SEARCH STRATEGY
The Cochrane Subfertility Review Group specialised register of controlled trials was searched".
SELECTION CRITERIA
SIxteen RCTs on the therapeutic use of androgens (clomiphene citrate or tamoxifen) in subfertile men were identified. Six trials were excluded.
DATA COLLECTION AND ANALYSIS
Methodological characteristics of trials Baseline characteristics of the studied groups Outcomes: Pregnancy rates, semen parameters (sperm concentration, motility and morphology), endocrinology (serum FSH, testosterone and oestradiol)
Topics: Fertility Agents, Male; Humans; Infertility, Male; Kallikreins; Male
PubMed: 10796695
DOI: 10.1002/14651858.CD000153 -
Journal of Clinical Sleep Medicine :... Jan 2015The purpose of this systematic review is to evaluate the diagnostic value of biological markers (exhaled breath condensate, blood, salivary and urinary) in the diagnosis... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
The purpose of this systematic review is to evaluate the diagnostic value of biological markers (exhaled breath condensate, blood, salivary and urinary) in the diagnosis of OSA in comparison to the gold standard of nocturnal PSG.
METHODS
Studies that differentiated OSA from controls based on PSG results, without age restriction, were eligible for inclusion. The sample of selected studies could include studies in obese patients and with known cardiac disease. A detailed individual search strategy for each of the following bibliographic databases was developed: Cochrane, EMBASE, MEDLINE, PubMed, and LILACS. The references cited in these articles were also crosschecked and a partial grey literature search was undertaken using Google Scholar. The methodology of selected studies was evaluated using the 14-item Quality Assessment Tool for Diagnostic Accuracy Studies.
RESULTS
After a two-step selection process, nine articles were identified and subjected to qualitative and quantitative analyses. Among them, only one study conducted in children and one in adults found biomarkers that exhibit sufficiently satisfactory diagnostic accuracy that enables application as a diagnostic method for OSA.
CONCLUSION
Kallikrein-1, uromodulin, urocotin-3, and orosomucoid-1 when combined have enough accuracy to be an OSA diagnostic test in children. IL-6 and IL-10 plasma levels have potential to be good biomarkers in identifying or excluding the presence of OSA in adults.
Topics: Adult; Biomarkers; Child; Child, Preschool; Female; Humans; Interleukin-10; Interleukin-6; Male; Middle Aged; Orosomucoid; Polysomnography; Reproducibility of Results; Sensitivity and Specificity; Sleep Apnea, Obstructive; Tissue Kallikreins; Urocortins; Uromodulin
PubMed: 25325575
DOI: 10.5664/jcsm.4358 -
Allergy and Asthma Proceedings Jan 2020Hereditary prekallikrein (Fletcher factor) deficiency is a rare condition characterized by a prolonged activated partial thromboplastin time. Inhibitors of plasma... (Meta-Analysis)
Meta-Analysis
Hereditary prekallikrein (Fletcher factor) deficiency is a rare condition characterized by a prolonged activated partial thromboplastin time. Inhibitors of plasma kallikrein have recently been approved for prophylaxis of hereditary angioedema and are under investigation for use in other indications. We attempted to conservatively assess the impact of long-term inhibition of this pathway by reviewing reported comorbidities in patients with hereditary prekallikrein deficiency. We searched several medical literature databases for publications that reported data from patients with hereditary prekallikrein deficiency (<10% of normal and/or shortening of activated partial thromboplastin time on increased incubation time). Data reporting of cardiovascular, bleeding, and autoimmune-related diseases were extracted. Of 1966 publications screened, 45 publications (which represented 53 patients with prekallikrein deficiency) were included. Among 53 identified patients with prekallikrein deficiency, 25 were explicitly defined as asymptomatic, with no comorbidities mentioned in another three cases. Another 16 of the 53 patients were described as having undergone surgery or dental extractions with no complications. Cardiovascular comorbidities were reported in 19 patients, mainly hypertension (9 patients) and cerebrovascular ischemia or stroke (5 patients). Excessive bleeding episodes after surgery were reported in four patients. Autoimmune-related diseases were reported for three patients (two with Graves disease and one with systemic lupus erythematosus). This review identified patients with hereditary prekallikrein deficiency who reported a spectrum of health outcomes from asymptomatic to infrequent reports of cardiovascular, bleeding, and autoimmune comorbidities. The majority of the reports did not indicate any association between prekallikrein deficiency and comorbidities; however, additional observation is required to confirm the long-term safety of plasma kallikrein inhibition.
Topics: Autoimmune Diseases; Blood Coagulation Disorders; Cardiovascular Diseases; Hemorrhage; Humans; Partial Thromboplastin Time; Prekallikrein
PubMed: 31888778
DOI: 10.2500/aap.2020.41.190005 -
Allergy and Asthma Proceedings Sep 2019Hereditary prekallikrein (Fletcher factor) deficiency is a rare condition characterized by a prolonged activated partial thromboplastin time. Inhibitors of plasma...
BACKGROUND
Hereditary prekallikrein (Fletcher factor) deficiency is a rare condition characterized by a prolonged activated partial thromboplastin time. Inhibitors of plasma kallikrein have recently been approved for prophylaxis of hereditary angioedema and are under investigation for use in other indications.
OBJECTIVE
We attempted to conservatively assess the impact of long-term inhibition of this pathway by reviewing reportedcomorbidities in patients with hereditary prekallikrein deficiency.
METHODS
We searched several medical literature databases for publications that reported data from patients with hereditaryprekallikrein deficiency (<10% of normal and/or shortening of activated partial thromboplastin time on increased incubationtime). Data reporting of cardiovascular, bleeding, and autoimmune-related diseases were extracted.
RESULTS
Of 1966 publications screened, 45 publications (which represented 53 patients with prekallikrein deficiency) wereincluded. Among 53 identified patients with prekallikrein deficiency, 25 were explicitly defined as asymptomatic, with no comorbidities mentioned in another three cases. Another 16 of the 53 patients were described as having undergone surgery or dental extractions with no complications. Cardiovascular comorbidities were reported in 19 patients, mainly hypertension (9 patients) and cerebrovascular ischemia or stroke (5 patients). Excessive bleeding episodes after surgery were reported in four patients. Autoimmune-related diseases were reported for three patients (two with Graves disease and onewith systemic lupus erythematosus).
CONCLUSION
This review identified patients with hereditary prekallikrein deficiency who reported a spectrum of health outcomes from asymptomatic to infrequent reports of cardiovascular, bleeding, and autoimmune comorbidities. The majority of the reports did not indicate any association between prekallikrein deficiency and comorbidities; however, additional observation is required to confirm the long-term safety of plasma kallikrein inhibition.
PubMed: 31530337
DOI: 10.2500/aap.2019.40.190005