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Archives of Disease in Childhood Apr 2005To undertake a systematic review of the literature reporting the prevalence of thrombophilia in children with a first arterial ischaemic stroke (AIS). (Meta-Analysis)
Meta-Analysis Review
AIMS
To undertake a systematic review of the literature reporting the prevalence of thrombophilia in children with a first arterial ischaemic stroke (AIS).
METHODS
Systematic review of case-control studies reporting data for prevalence of protein C, S, and antithrombin (AT) deficiencies, activated protein C resistance (APCr), total plasma homocysteine >95th centile, the thrombophilic mutations factor V1691 GA, prothrombin 20210GA, and MTHFR C677T in children with first, radiologically confirmed, AIS.
RESULTS
Of 1437 potentially relevant citations, 18 met inclusion criteria. A total of 3235 patients and 9019 controls had been studied. Results of meta-analyses were expressed as pooled odds ratios (OR) relating the prevalence of the thrombophilic condition in children with AIS to that in controls. The pooled OR (and 95% CI) were: protein C deficiency, 6.49 (2.96 to 14.27); protein S deficiency, 1.14 (0.34 to 3.80); AT deficiency, 1.02 (0.28 to 3.67); APCr, 1.34 (0.16 to 11.52); FV1691 GA, 1.22 (0.80 to 1.87); PT20210GA, 1.10 (0.51 to 2.34); MTHFR C677T, 1.70 (1.23 to 2.34); and total plasma homocysteine >95th centile, 1.36 (0.53 to 3.51). There was no statistical heterogeneity within these data.
CONCLUSIONS
All factors examined were more common in children with first AIS than in controls, and significantly so for protein C deficiency and the MTHFR C677T mutation. The implications of thrombophilia for prognosis and recurrence need to be established before clinical recommendations can be made regarding investigation and treatment of children with AIS.
Topics: Brain Ischemia; Case-Control Studies; Chi-Square Distribution; Child; Factor V; Homocysteine; Humans; Methylenetetrahydrofolate Reductase (NADPH2); Mutation; Odds Ratio; Prognosis; Thrombophilia
PubMed: 15781933
DOI: 10.1136/adc.2004.049163 -
Caries Research 2022Salivary proteins play an important role in repairing mechanisms of damaged tissues and the maintenance of oral health. However, there is a dearth of information in the...
Salivary proteins play an important role in repairing mechanisms of damaged tissues and the maintenance of oral health. However, there is a dearth of information in the literature regarding the concentrations of salivary proteins in caries-free (CF) and caries-active (CA) subjects. Hence, this systematic review was conducted to update our previous systematic review published in 2013 that aimed to assess the association between caries and salivary proteins by comparing CF and CA individuals. Thereby, evaluating the possibility of whether salivary proteins can be regarded as biomarkers for caries. An extensive search of studies was conducted using PubMed, EMBASE, Clarivate Analytics' Web of Science, and Elsevier's Scopus between July 2012 and January 2022, without any language restriction. Manual searching in Google Scholar and evaluation of bibliographies of the included studies were also undertaken. The Newcastle-Ottawa Scale was used to assess the risk of bias (RoB) within the included studies. Of 22 included studies, 1,551 human subjects (range: 30-213 participants) were recruited, of which 848 individuals (54.7%) were CA and 703 (45.3%) were CF. Regarding the utilization of DMFT as the caries index, high variability was observed across different articles. A statistically significant increase in the salivary levels of alpha-amylase, acidic proline-rich protein-1, histatin-5, lactoperoxidase, and mucin-1 was found in CA patients, while the salivary levels of carbonic anhydrase 6, proteinase-3, and statherin were observed to be significantly increased in CF subjects. Conflicting results were found regarding the salivary levels of immunoglobulin A and total proteins among CA and CF subjects. The included studies were categorized as low RoB (n = 15), medium RoB (n = 4), and high RoB (n = 3). Due to significant heterogeneity among the included studies, no meta-analysis could be performed. In conclusion, the salivary levels of protein(s) might be a useful biomarker for caries diagnosis, especially alpha-amylase, acidic proline-rich protein-1, histatin-5, lactoperoxidase, mucin-1, carbonic anhydrase 6, proteinase-3, and statherin. However, their diagnostic value must be verified by large-scale prospective studies.
Topics: Humans; Mucin-1; Dental Caries; Histatins; Lactoperoxidase; Prospective Studies; Salivary Proteins and Peptides; Biomarkers; Proline; alpha-Amylases; Peptide Hydrolases
PubMed: 36116431
DOI: 10.1159/000526942 -
Blood Reviews Jun 2004Thromboembolic disease (TE) has been described as the new epidemic of tertiary paediatrics, and no where is this more evident than in the neonatal population. As... (Review)
Review
Thromboembolic disease (TE) has been described as the new epidemic of tertiary paediatrics, and no where is this more evident than in the neonatal population. As survival of premature and sick newborns has improved, the frequency of complications associated with intensive supportive therapy and monitoring has increased. Clinically significant thrombosis is emerging as one of the more common complications associated with improved neonatal outcome. The long-term implications of neonatal thrombosis are only just being realised. This systematic review will consider the epidemiology, diagnostic strategies, and outcome for both arterial and venous TE in neonates. The role of inherited thrombophilic abnormalities, and the evidence for anticoagulation therapy will also be considered. The lack of high level evidence in determining optimum therapy is obvious. Further research regarding diagnostic strategies, and optimal therapies is urgently needed.
Topics: Catheterization, Peripheral; Catheters, Indwelling; Child; Factor V; Female; Genetic Markers; Genetic Predisposition to Disease; Humans; Infant, Newborn; Infant, Newborn, Diseases; Male; Protein C Deficiency; Protein S Deficiency; Thromboembolism; Thrombolytic Therapy; Venous Thrombosis
PubMed: 15010146
DOI: 10.1016/S0268-960X(03)00042-0 -
Journal of Thrombosis and Haemostasis :... Dec 2020Retinal vascular occlusion is a leading cause of sight loss. Both retinal artery occlusion (RAO) and retinal vein occlusion (RVO) have been associated with... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Retinal vascular occlusion is a leading cause of sight loss. Both retinal artery occlusion (RAO) and retinal vein occlusion (RVO) have been associated with hypercoagulable states; however, the burden of thrombophilia in these patients is unclear.
OBJECTIVES
This study aims at estimating the prevalence of inherited and acquired thrombophilias in adults with RAO or RVO through a systematic review and meta-analysis of the literature.
PATIENTS/METHODS
PubMed and EMBASE were systematically searched from inception to 29 February 2020. All studies reporting prevalences of factor V Leiden (FVL) and prothrombin (F-II) G20210A mutations, methylenetetrahydrofolate reductase (MTHFR) C677T and plasminogen activator inhibitor (PAI) 4G polymorphisms, antithrombin III (AT-III), protein C (PC) and protein S (PS) activity deficiencies, hyperhomocysteinemia, and antiphospholipid (APL) antibodies in adults with RAO or RVO were included. Pooled prevalences and 95% confidence intervals (CI) were calculated.
RESULTS
Ninety-five studies were included; FVL and F-II mutations were found in 6% (95% CI: 5-8) and 3% (95% CI: 2-4) of individuals with RVO, respectively, whereas AT-III, PC, and PS activity deficiencies were found in <2%. The MTHFR C677T and PAI 4G homozygous polymorphism were observed in 13% (95% CI: 10-17) and 23% (95% CI: 16-31) of RVO, respectively; 8% presented APL antibodies. Similar findings were observed in individuals with RAO.
CONCLUSIONS
Compared with healthy subjects, patients with retinal vascular occlusion showed similar prevalences of inherited and acquired thrombophilias. These findings do not support routine thrombophilia screening in individuals with RAO or RVO.
Topics: Adult; Factor V; Humans; Methylenetetrahydrofolate Reductase (NADPH2); Prothrombin; Retinal Vein Occlusion; Risk Factors; Thrombophilia
PubMed: 32805772
DOI: 10.1111/jth.15068 -
Circulation Apr 2010The aim of this study was to estimate the impact of thrombophilia on risk of first childhood stroke through a meta-analysis of published observational studies. (Meta-Analysis)
Meta-Analysis Review
Impact of thrombophilia on risk of arterial ischemic stroke or cerebral sinovenous thrombosis in neonates and children: a systematic review and meta-analysis of observational studies.
BACKGROUND
The aim of this study was to estimate the impact of thrombophilia on risk of first childhood stroke through a meta-analysis of published observational studies.
METHODS AND RESULTS
A systematic search of electronic databases (Medline via PubMed, EMBASE, OVID, Web of Science, The Cochrane Library) for studies published from 1970 to 2009 was conducted. Data on year of publication, study design, country of origin, number of patients/control subjects, ethnicity, stroke type (arterial ischemic stroke [AIS], cerebral venous sinus thrombosis [CSVT]) were abstracted. Publication bias indicator and heterogeneity across studies were evaluated, and summary odds ratios (ORs) and 95% confidence intervals (CIs) were calculated with fixed-effects or random-effects models. Twenty-two of 185 references met inclusion criteria. Thus, 1764 patients (arterial ischemic stroke [AIS], 1526; cerebral sinus venous thrombosis [CSVT], 238) and 2799 control subjects (neonate to 18 years of age) were enrolled. No significant heterogeneity was discerned across studies, and no publication bias was detected. A statistically significant association with first stroke was demonstrated for each thrombophilia trait evaluated, with no difference found between AIS and CSVT. Summary ORs (fixed-effects model) were as follows: antithrombin deficiency, 7.06 (95% CI, 2.44 to 22.42); protein C deficiency, 8.76 (95% CI, 4.53 to 16.96); protein S deficiency, 3.20 (95% CI, 1.22 to 8.40), factor V G1691A, 3.26 (95% CI, 2.59 to 4.10); factor II G20210A, 2.43 (95% CI, 1.67 to 3.51); MTHFR C677T (AIS), 1.58 (95% CI, 1.20 to 2.08); antiphospholipid antibodies (AIS), 6.95 (95% CI, 3.67 to 13.14); elevated lipoprotein(a), 6.27 (95% CI, 4.52 to 8.69), and combined thrombophilias, 11.86 (95% CI, 5.93 to 23.73). In the 6 exclusively perinatal AIS studies, summary ORs were as follows: factor V, 3.56 (95% CI, 2.29 to 5.53); and factor II, 2.02 (95% CI, 1.02 to 3.99).
CONCLUSIONS
The present meta-analysis indicates that thrombophilias serve as risk factors for incident stroke. However, the impact of thrombophilias on outcome and recurrence risk needs to be further investigated.
Topics: Brain Ischemia; Child; Humans; Infant, Newborn; Risk Factors; Sinus Thrombosis, Intracranial; Stroke; Thrombophilia
PubMed: 20385928
DOI: 10.1161/CIRCULATIONAHA.109.913673 -
Thrombosis and Haemostasis Jun 2017Data on paediatric pulmonary embolism (PE) are scarce. We sought to systematically review the current literature on childhood PE and conducted a search on paediatric PE... (Review)
Review
Data on paediatric pulmonary embolism (PE) are scarce. We sought to systematically review the current literature on childhood PE and conducted a search on paediatric PE via PubMed (1946-2013) and Embase (1980-2013). There was significant heterogeneity in reported data. Two patterns were noted: classic thromboembolic PE (TE-PE) and in situ pulmonary artery thrombosis (ISPAT). Mean age of presentation for TE-PE was 14.86 years, and 51 % of cases were males. The commonest method for diagnosis of TE-PE was contrast CT with angiography (74 % of patients). The diagnosis of TE-PE was often delayed. Although 85 % of children with TE-PE had an elevated D-dimer at presentation, it was non-discriminatory for the diagnosis. In paediatric TE-PE, the prevalence of central venous catheters was 23 %, immobilisation 38 %, systemic infection 31 % and obesity 13 %, elevated Factor VIII or von Willebrand factor levels 27 %, Protein C deficiency 17 %, Factor V Leiden 14 % and Protein S deficiency 7 %. In patients with TE-PE, pharmacologic thrombolysis was used in 29 %; unfractionated heparin was the most common initial anticoagulant treatment in 64 % and low-molecular-weight heparins the most common follow-up treatment in 83 %. Duration of anticoagulant therapy was variable and death was reported in 26 % of TE-PE patients. In contrast to TE-PE, patients with ISPAT were not investigated systematically for presence of thrombophilia, had more surgical interventions as the initial management and were often treated with anti-platelet medications. This review summarises important data and identifies gaps in the knowledge of paediatric PE, which may help to design future studies.
Topics: Adolescent; Angiography; Anticoagulants; Comorbidity; Female; Heparin; Humans; Male; Pneumoradiography; Prevalence; Pulmonary Artery; Pulmonary Embolism; Survival Analysis; Thromboembolism; Thrombosis
PubMed: 28331932
DOI: 10.1160/TH16-07-0529 -
Clinical Journal of the American... Jul 2008Calciphylaxis, or calcific uremic arteriolopathy, is a well-described entity in end-stage kidney disease and renal transplant patients; however, little systematic... (Review)
Review
BACKGROUND AND OBJECTIVES
Calciphylaxis, or calcific uremic arteriolopathy, is a well-described entity in end-stage kidney disease and renal transplant patients; however, little systematic information is available on calciphylaxis from nonuremic causes. This systematic review was designed to characterize etiologies, clinical features, laboratory abnormalities, and prognosis of nonuremic calciphylaxis.
DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS
A systematic review of literature for case reports and case series of nonuremic calciphylaxis was performed. Cases included met the operational definition of nonuremic calciphylaxis-histopathologic diagnosis of calciphylaxis in the absence of end-stage kidney disease, renal transplantation, or acute kidney injury requiring renal replacement therapy.
RESULTS
We found 36 cases (75% women, 63% Caucasian, aged 15 to 82 yr) of nonuremic calciphylaxis. Primary hyperparathyroidism, malignancy, alcoholic liver disease, and connective tissue disease were the most common reported causes. Preceding corticosteroid use was reported for 61% patients. Protein C and S deficiencies were seen in 11% of patients. Skin lesions were morphologically similar to calcific uremic arteriolopathy. Mortality rate was 52%, with sepsis being the leading cause of death.
CONCLUSION
Calciphylaxis should be considered while evaluating skin lesions in patients with predisposing conditions even in the absence of end-stage kidney disease and renal transplantation. Nonuremic calciphylaxis is reported most often in white women. Mineral abnormalities that are invoked as potential causes in calcific uremic arteriolopathy are often absent, suggesting that heterogeneous mechanisms may contribute to its pathogenesis. Nonuremic calciphylaxis is associated with high mortality, and there is no known effective treatment.
Topics: Adolescent; Adrenal Cortex Hormones; Adult; Aged; Aged, 80 and over; Biomarkers; Calciphylaxis; Connective Tissue Diseases; Female; Humans; Hyperparathyroidism, Primary; Liver Diseases, Alcoholic; Male; Middle Aged; Neoplasms; Prognosis; Protein C Deficiency; Protein S Deficiency; Risk Factors; Sepsis; Skin; Skin Diseases
PubMed: 18417747
DOI: 10.2215/CJN.00530108 -
Frontiers in Immunology 2021The immune system is unique among all biological sub-systems in its usage of DNA-editing enzymes to introduce targeted gene mutations and double-strand DNA breaks to...
Evolutionary Comparative Analyses of DNA-Editing Enzymes of the Immune System: From 5-Dimensional Description of Protein Structures to Immunological Insights and Applications to Protein Engineering.
The immune system is unique among all biological sub-systems in its usage of DNA-editing enzymes to introduce targeted gene mutations and double-strand DNA breaks to diversify antigen receptor genes and combat viral infections. These processes, initiated by specific DNA-editing enzymes, often result in mistargeted induction of genome lesions that initiate and drive cancers. Like other molecules involved in human health and disease, the DNA-editing enzymes of the immune system have been intensively studied in humans and mice, with little attention paid (< 1% of published studies) to the same enzymes in evolutionarily distant species. Here, we present a systematic review of the literature on the characterization of one such DNA-editing enzyme, activation-induced cytidine deaminase (AID), from an evolutionary comparative perspective. The central thesis of this review is that although the evolutionary comparative approach represents a minuscule fraction of published works on this and other DNA-editing enzymes, this approach has made significant impacts across the fields of structural biology, immunology, and cancer research. Using AID as an example, we highlight the value of the evolutionary comparative approach in discoveries already made, and in the context of emerging directions in immunology and protein engineering. We introduce the concept of 5-dimensional (5D) description of protein structures, a more nuanced view of a structure that is made possible by evolutionary comparative studies. In this higher dimensional view of a protein's structure, the classical 3-dimensional (3D) structure is integrated in the context of real-time conformations and evolutionary time shifts (4 dimension) and the relevance of these dynamics to its biological function (5 dimension).
Topics: Animals; Biological Evolution; Cytidine Deaminase; DNA; Humans; Protein Conformation; Protein Engineering
PubMed: 34135887
DOI: 10.3389/fimmu.2021.642343 -
Cureus Apr 2020Cerebral venous sinus thrombosis (CVST) is a rare condition characterized by elevated intracranial pressure due to impaired cerebral venous drainage, potentially... (Review)
Review
Cerebral venous sinus thrombosis (CVST) is a rare condition characterized by elevated intracranial pressure due to impaired cerebral venous drainage, potentially leading to life-threatening consequences. We searched the PubMed electronic database for 'cerebral venous sinus thrombosis' and 'prothrombotic' cases reported in adults (19+ years) and conducted a systematic review for the published literature in the English language pooled with a case from our institution. Data were analyzed regarding patient demographics, risk factors, clinical features, treatment modalities, and outcomes when available. Thirty cases of CVST were identified (29 case reports, of whom two were described in a case series, and the one case from our institution). The patients' mean age was 39 years (range: 19 - 65). The male: female ratio was 1.14:1. The majority (73.3%) had at least one preexisting risk factor, with prescription drug use being the most common risk factor (33.3%) shared among all patients. Most patients (83.3%) presented with at least two symptoms. The most common presenting symptoms were headache (70%), gastrointestinal disturbance (50%), and seizures (40%). Focal deficits (36.7%), vision disturbances (30%), and altered consciousness (20%) were the remaining presenting complaints. Twelve cases (40%) commented on papilledema, with 10 (83.3%) having papilledema present. Anticoagulation abnormalities were examined in 26 cases (86.7%), out of which four cases (15.4%) had isolated protein S (PS) deficiency, three cases (11.5%) had isolated antithrombin III (ATIII) deficiency, and one case (3.8%) had isolated protein C (PC) deficiency. The most common initial imaging modality (22 cases, 73.3%), and most commonly used overall (23 cases, 76.7%), was computed tomography (CT). Magnetic resonance imaging (MRI) was the second most common imaging modality for initial use (five cases, 16.7%), diagnosis or confirmation of CVST (eight cases, 26.7%), and overall (21 cases, 70%). Heparin treatment was involved in the treatment of 18 cases (60%), and warfarin treatment was used in 10 cases (33.3%). Heparin-warfarin combination treatment was utilized in eight cases (26.7%). Most patients survived (28 cases, 93.3%), while the two remaining patients died secondary to brain death from the CVST (6.7%). The findings from this study highlight the clinical characteristics of CVST. Therefore, this study aims to increase awareness of this rare entity. Physicians should maintain a high index of suspicion in order to diagnose patients presenting in the proper clinical context, given this case shares various forms of presentations with other common clinical conditions but requires long-term anticoagulation.
PubMed: 32411555
DOI: 10.7759/cureus.7654 -
Thrombosis Research Mar 2018Despite high rates of venous thromboembolism (VTE) among patients with hematologic malignancies, few tools exist to assist providers in identifying those patients at... (Review)
Review
INTRODUCTION
Despite high rates of venous thromboembolism (VTE) among patients with hematologic malignancies, few tools exist to assist providers in identifying those patients at highest risk for this potentially fatal complication. Laboratory biomarkers, such as d-dimer, have demonstrated utility in some clinical settings to distinguish patients at increased risk.
MATERIALS AND METHODS
We performed a systematic review of the literature utilizing search terms including "biomarker", "venous thromboembolism", "hematologic malignancy", "lymphoma", "myeloma" and "leukemia" in the Medline database. A total of 25 studies investigating laboratory biomarkers of increased thrombotic risk in the setting of hematologic malignancy were identified and included in this review.
RESULTS AND CONCLUSIONS
The most studied biomarkers, d-dimer and fibrinogen, demonstrated some degree of efficacy in identifying high-risk patients at levels >4.0 mg/L or <1.0 g/L respectively. Additional markers which demonstrated promise included thrombin generation, mean platelet volume, soluble VEGF, soluble P-selectin and extracellular vesicles. Other biomarkers reviewed, which did not consistently demonstrate significant associations with VTE included prothrombin fragments F1 + 2, factor VIII, protein C, protein S, von Willebrand antigen and activity, antithrombin, thrombin antithrombin complex, antiphospholopid antibody, plasminogen activator inhibitor, tissue factor pathway inhibitor and several variants associated with known hypercoagulable states (factor V Leiden, prothrombin gene variant, methylenetetrahydrofolate reductase variant). Data to support any of the biomarkers discussed here in routine clinical decision-making are currently lacking, but additional investigation in clinical studies, ideally in combination with clinical factors known to be associated with increased thrombotic risk, is warranted.
Topics: Biomarkers; Female; Hematologic Neoplasms; Humans; Male; Risk Factors; Venous Thromboembolism
PubMed: 29407626
DOI: 10.1016/j.thromres.2018.01.037