scholarly journals P450 Oxidoreductase Deficiency: A Systematic Review and Meta-analysis of Genotypes, Phenotypes, and Their Relationships

2019 ◽  
Vol 105 (3) ◽  
pp. e42-e52 ◽  
Author(s):  
Benjamin Dean ◽  
Georgina L Chrisp ◽  
Maria Quartararo ◽  
Ann M Maguire ◽  
Shihab Hameed ◽  
...  
Keyword(s):  
Adrenal Insufficiency ◽  
Case Reports ◽  
Data Extraction ◽  
Meta Analysis ◽  
Genetic Disorder ◽  
Disorders Of Sexual Development ◽  
Skeletal Malformation ◽  
P450 Oxidoreductase ◽  
Skeletal Malformations ◽  
In Pregnancy

Abstract Context P450 oxidoreductase deficiency (PORD) is a rare genetic disorder that is associated with significant morbidity. However there has been limited analysis of reported PORD cases. Objective To determine, based on the cohort of reported PORD cases, genotype-phenotype relationships for skeletal malformations, maternal virilisation in pregnancy, adrenal insufficiency, and disorders of sexual development (DSD). Data Sources PubMed and Web of Science from January 2004 to February 2018. Study Selection Published case reports/series of patients with PORD. Eligible patients were unique, had biallelic mutations, and their clinical features were reported. Data Extraction Patient data were manually extracted from the text of case reports/series. A malformation score, representing the severity of skeletal malformations, was calculated for each patient. Data Synthesis Of the 211 patients published in the literature, 90 were eligible for inclusion. More than 60 unique mutations were identified in this cohort. Four groups of mutations were identified, through regression modeling, as having significantly different skeletal malformation scores. Maternal virilization in pregnancy, reported for 21% of patients, was most common for R457H mutations. Adrenal insufficiency occurred for the majority of patients (78%) and was typically mild, with homozygous R457H mutations being the least deficient. DSD affected most patients (72%), but were less common for males (46XY) with homozygous R457H mutations. Conclusions PORD is a complex disorder with many possible mutations affecting a large number of enzymes. By analyzing the cohort of reported PORD cases, this study identified clear relationships between genotype and several important phenotypic features.

The Contact System

2002 ◽  
Vol 126 (11) ◽  
pp. 1382-1386 ◽  
Author(s):  
Craig S. Kitchens
Keyword(s):  
Antiphospholipid Syndrome ◽  
English Language ◽  
Case Reports ◽  
Data Extraction ◽  
Meta Analysis ◽  
Factor Xii ◽  
Activity Levels ◽  
Medline Search ◽  
Apparent Association

Abstract Objectives.—To review the literature for conditions, diseases, and disorders that affect activity of the contact factors, and further to review the literature for evidence that less than normal activity of any of the contact factors may be associated with thrombophilia. Data Sources.—MEDLINE search for English-language articles published from 1988 to 2001 and pertinent references contained therein, as well as search of references in recent relevant articles and reviews. Study Selection.—Relevant clinical and laboratory information was extracted from selected articles. Meta-analysis was not feasible because of heterogeneity of reports. Data Extraction and Synthesis.—Evidence for association of altered levels of the contact factors and thrombophilia was sought. A wide variety of disorders is associated with decreased activity of the contact factors; chief among these disorders are liver disease, hepatic immaturity of newborns, the antiphospholipid syndrome, and, for factor XII, being of Asian descent. These disorders are more common than homozygous deficiency. The few series and case reports of thrombophilic events in patients homozygous for deficiency of contact factors are not persuasive enough to support causality. The apparent association between levels consistent with heterozygosity (40%–60% of normal) of any of the contact factors (but especially factor XII) in persons with antiphospholipid antibodies appears to be due to falsely decreased in vitro activity levels of these factors, which are normal on antigenic testing. The apparent association with thrombosis is better explained by the antiphospholipid syndrome than by the modest reduction of the levels of contact factors. Conclusions.—Presently, it is not recommended to measure activity of contact factors during routine evaluation of patients who have suffered venous or arterial thromboembolism or acute coronary syndromes.

Timely Revisit of Proprioceptive Deficits in Adolescent Idiopathic Scoliosis: A Systematic Review and Meta-Analysis

2021 ◽  
pp. 219256822110668
Author(s):  
Kenney K. L. Lau ◽  
Karlen K. P. Law ◽  
Kenny Y. H. Kwan ◽  
Jason P. Y. Cheung ◽  
Kenneth M. C. Cheung ◽  
...  
Keyword(s):  
Systematic Review ◽  
Adolescent Idiopathic Scoliosis ◽  
Idiopathic Scoliosis ◽  
Case Reports ◽  
Data Extraction ◽  
Meta Analysis ◽  
Detection Threshold ◽  
Mean Difference ◽  
Case Control Studies ◽  
Meta Analyses

Study Design Systematic review and meta-analysis Objectives The present review aimed to summarize the evidence regarding differences in proprioception between children with and without adolescent idiopathic scoliosis (AIS). Methods Seven electronic databases were searched from their inception to April 10, 2021. Articles were included if they involved: (1) AIS patients aged between 10 and 18 years, (2) measurements of proprioceptive abilities, and (3) comparisons with non-AIS controls. Animal studies, case reports, commentaries, conference proceedings, research protocols, and reviews were excluded. Two reviewers independently conducted literature screening, data extraction, risks of bias assessments, and quality of evidence evaluations. Relevant information was pooled for meta-analyses. Results From 432 identified citations, 11 case-control studies comprising 1121 participants were included. The meta-analyses showed that AIS participants displayed proprioceptive deficits as compared to non-AIS controls. Moderate evidence supported that AIS participants showed significantly larger repositioning errors than healthy controls (pooled mean difference = 1.27 degrees, P < .01). Low evidence substantiated that AIS participants had significantly greater motion detection threshold (pooled mean difference = 1.60 degrees, P < .01) and abnormal somatosensory evoked potentials (pooled mean difference = .36 milliseconds, P = .01) than non-AIS counterparts. Conclusions Consistent findings revealed that proprioceptive deficits occurred in AIS patients. Further investigations on the causal relationship between AIS and proprioception, and the identification of the subgroup of AIS patients with proprioceptive deficit are needed.

scholarly journals ASSOCIATION BETWEEN ETHNICITY AND SEVERE COVID-19 DISEASE: A SYSTEMATIC REVIEW AND META-ANALYSIS.

2020 ◽  
Author(s):  
Antony Raharja ◽  
Alice Tamara ◽  
Li Teng Kok
Keyword(s):  
Systematic Review ◽  
Risk Factor ◽  
Ethnic Minorities ◽  
Independent Risk Factor ◽  
Case Reports ◽  
Data Extraction ◽  
Meta Analysis ◽  
Risk Of Bias ◽  
Research Database ◽  
All Cause Mortality

Background: Multiple reports suggested disproportionate impact of Covid-19 on ethnic minorities. Whether ethnicity is an independent risk factor for severe Covid-19 illness is unclear. Purpose: Review the association between ethnicity and poor Covid-19 outcomes including all-cause mortality, hospitalisation, critical care admission, respiratory and kidney failure. Data Sources: MEDLINE, EMBASE, Cochrane COVID-19 Study Register, WHO COVID-19 Global Research Database up to 15/06/2020, and preprint servers. No language restriction. Study Selection: All studies providing ethnicity-aggregated data on the pre-specified outcomes, except case reports or interventional trials Data Extraction: Pairs of investigators independently extracted data, assessed risk of bias using Newcastle-Ottawa scale (NOS), and rated certainty of evidence following GRADE framework. Data Synthesis: Seventy-two articles (59 cohort studies with 17,950,989 participants; 13 ecological studies; 54 US-based and 15 UK-based; 41 peer-reviewed) were included for systematic review and 45 for meta-analyses. Risk of bias was low, with median NOS of 7 (interquartile range 6-8). In the unadjusted analyses, compared to white ethnicity, all-cause mortality risk was similar in Black (RR:0.96 [95%CI: 0.83-1.08]), Asian (RR:0.99 [0.85-1.16]) but reduced in Hispanic ethnicity (RR:0.69 [0.57-0.84]). Age and sex-adjusted-risks were significantly elevated for Black (HR:1.38 [1.09-1.75]) and Asian (HR:1.42 [1.15-1.75]), but not for Hispanic (RR:1.14 [0.93-1.40]). Further adjusting for comorbidities attenuated these association to non-significance; Black (HR:0.95 [0.72-1.25]); Asian (HR:1.17 [0.84-1.63]); Hispanic (HR:0.94 [0.63-1.44]). Similar results were observed for other outcomes. In subgroup analysis, there is a trend towards greater disparity in outcomes for UK ethnic minorities, especially hospitalisation risks. Limitations: Paucity of evidence on native ethnic groups, and studies outside US and UK. Conclusions: Currently available evidence cannot confirm ethnicity as an independent risk factor for severe Covid-19 illness, but indicates that disparity may be partially attributed to greater burden of comorbidities. Registration: PROSPERO, CRD42020188421 Funding source: none

Combined homozygous 21 hydroxylase with heterozygous P450 oxidoreductase mutation in a Saudi boy presented with hypertension

2020 ◽  
Vol 13 (9) ◽  
pp. e233942
Author(s):  
Aida Aljabri ◽  
Fatimah Alnaim ◽  
Yasin Alsaleh
Keyword(s):  
Adrenal Insufficiency ◽  
Clinical Manifestations ◽  
Ambiguous Genitalia ◽  
Sterol Synthesis ◽  
Gene Encoding ◽  
Key Enzymes ◽  
P450 Oxidoreductase ◽  
Sex Development ◽  
Skeletal Malformations ◽  
New Variant

Congenital adrenal hyperplasia (CAH) comprises a group of inherited autosomal recessive disorders characterised by defective cortisol biosynthesis, compensatory increases in corticotrophin secretion and adrenocortical hyperplasia. The characteristics of the biochemical and clinical phenotype depend on the specific enzymatic defect. 21-hydroxylase deficiency is estimated to account for 90%–95% of all CAH cases. Although there are many variants of CAH, a new variant is found secondary to a mutation in the gene encoding the protein P450 oxidoreductase (POR) in which the electron is granted to all microsomal P450 enzymes type II. In 2004, it was discovered that this new CAH disease was attributable to the POR gene mutation. POR facilitates electron transfer from Nicotinamide adenine dinucleotide phosphate (NADPH) to key enzymes involved in steroid and sterol synthesis and metabolism. POR deficiency causes partial and combined impairment of the key enzymes involved in steroidogenesis: P450c17 (17α-hydroxylase/17,20 lyase), P450c21 (21-hydroxylase) and P450aro (aromatase). Clinically, mutant POR manifests with disordered sex development, adrenal insufficiency and skeletal malformations. However, each enzyme may be differently compromised in the same patient. This difference in the clinical manifestations secondary to the variability in enzymatic impairments ranges from ambiguous genitalia in both sexes, adrenal insufficiency associated or not to bone malformations, to abnormal laboratory results in the neonatal screening test of asymptomatic newborns. We report here a case of a 46, XY patient with normal male genitalia associated with hypertension not related to fludrocortisone in which genetic study showed that a homozygous mutation in the CYP21A2 also carries the heterozygous missense variant of unclear pathogenicity in the POR gene.Although there are many variants of CAH, a new variant is found secondary to a mutation in the gene encoding the protein P450 oxidoreductase (POR) which therefore the electron is granted to all microsomal P450 enzymes type II. In 2004, it was mentioned by Fluck and his colleagues that this new CAH disease was attributable to the POR gene mutation.POR facilitates electron transfer from NADPH to key enzymes involved in steroid and sterol synthesis and metabolism.POR deficiency causes partial and combined impairment of the key enzymes involved in steroidogenesis: P450c17 (17α- hydroxylase/17,20 lyase), P450c21 (21-hydroxylase) and P450aro (aromatase).Clinically, Mutant POR manifests with disordered sex development, adrenal insufficiency and skeletal malformations.However, each enzyme may be differently compromised in the same patient. This difference in the clinical manifestations secondary to the variability in enzymatic impairments, it is ranging from ambiguous genitalia in both sexes, adrenal insufficiency associated or not to bone malformations, to abnormal laboratory results in the neonatal screening test of asymptomatic newborns.

Teratogenic Risk of Statins in Pregnancy

2012 ◽  
Vol 46 (10) ◽  
pp. 1419-1424 ◽  
Author(s):  
Laura M Godfrey ◽  
John Erramouspe ◽  
Kevin W Cleveland
Keyword(s):  
Case Reports ◽  
Data Extraction ◽  
Current Trend ◽  
Case Series ◽  
Teratogenic Risk ◽  
Study Selection ◽  
Pubmed Search ◽  
Teratogenic Potential ◽  
Statin Use ◽  
In Pregnancy

Objective: To evaluate the teratogenic potential of statins in women of child-bearing age. Data Sources: A PubMed search (1980-September 2012) was performed using the search terms statin and pregnancy, then repealed using statin and teratogenicity. Results were limited to articles published in English reporting on use of statins in humans. Study Selection and Data Extraction: All articles presenting data on pregnancy outcomes after statin use during any trimester of pregnancy were included. Three case reports, 2 case series, 2 systematic reviews, 2 registry-based studies, and 1 prospective observational cohort study were reviewed. Data Synthesis: Since initial premarketing studies of lovastatin in animals, terato-genesis has been assumed to be a classwide function of statins' mechanism of action. Data from human exposure during pregnancy have been gathered and analyzed in a variety of study formats to formulate useable conclusions on statins' actual teratogenic risk and pattern of associated birth defects. Although the current trend is that actual risk is lower than once thought, the available literature is limited by potential reporting bias, contains overlap in the data, and frequently lacks numbers of total exposures to statins during pregnancy with reported malformations. Additionally, no human studies included data on the 2 newest statins (rosuvastatin, pitavastatin); the more lipophilic statins (lovastatin, simvastatin) have the most experience and thus have more evidence related to teratogenic potential. Conclusions: Human teratogenic risk has not been proven nor has it been ruled out by the available data on statin use in pregnancy. Possible differences in risk between individual statins require further evaluation. Additional data, including prospective observational cohorts with inadvertent maternal exposure to statins during early weeks of gestation, should further help to clarify appropriate recommendations for statin use in this population.

scholarly journals A Meta-Analysis of the Prevalence of Cardiac Valvulopathy in Patients With Hyperprolactinemia Treated With Cabergoline

2018 ◽  
Vol 104 (2) ◽  
pp. 523-538 ◽  
Author(s):  
Craig E Stiles ◽  
Eugene T Tetteh-Wayoe ◽  
Jonathan P Bestwick ◽  
Richard P Steeds ◽  
William M Drake
Keyword(s):  
Tricuspid Regurgitation ◽  
Clinical Symptoms ◽  
Single Case ◽  
Case Reports ◽  
Data Extraction ◽  
Meta Analysis ◽  
Pituitary Tumors ◽  
Inclusion Criteria ◽  
Case Control Studies ◽  
Meta Analyses

Abstract Context Cabergoline is first-line treatment for most patients with lactotrope pituitary tumors and hyperprolactinemia. Its use at high dosages in Parkinson disease (PD) has largely been abandoned because of its association with the development of a characteristic restrictive cardiac valvulopathy. Whether similar valvular changes occur in patients receiving lower dosages for treatment of hyperprolactinemia is unclear, although stringent regulatory recommendations for echocardiographic screening exist. Objective To conduct a meta-analysis exploring any link between the use of cabergoline for the treatment of hyperprolactinemia and clinically significant cardiac valvulopathy. Data Sources Full-text articles published through January 2017 were found via PubMed and selected according to strict inclusion criteria. Study Selection All case-control studies were included where patients had received ≥6 months of cabergoline treatment for hyperprolactinemia. Single case reports, previous meta-analyses, review articles, and articles pertaining solely to PD were excluded. Of 76 originally selected studies, 13 met inclusion criteria. Data Extraction Desired data were compiled and extracted from articles by independent observers. Each also independently graded article quality (bias) and met to reach consensus. Data Synthesis More tricuspid regurgitation was observed (OR 3.74; 95% CI, 1.79 to 7.8; P &lt; 0.001) in the cabergoline-treated patients compared with controls. In no patient was tricuspid valve dysfunction diagnosed as a result of clinical symptoms. There was no significant increase in any other valvulopathy. Conclusions Treatment with low-dose cabergoline in hyperprolactinemia appears to be associated with an increased prevalence of tricuspid regurgitation. The clinical significance of this finding is unclear and warrants further investigation.

Neurofibromatosis in Pregnancy

2016 ◽  
Vol 1 (2) ◽  
pp. 91-92
Author(s):  
HK Premi ◽  
Sonika Dahiya ◽  
Shobha Mukherjee
Keyword(s):  
English Language ◽  
Case Reports ◽  
Genetic Disorder ◽  
Genetic Diseases ◽  
Real Situation ◽  
Current Information ◽  
The Past ◽  
Maternal Disease ◽  
Language Literature ◽  
In Pregnancy

ABSTRACT Neurofibromatosis (NF) is one of the most frequent genetic diseases in humans. It is less common to find pregnancy in NF patients. It may not reflect the real situation as most current information on pregnancy and NF is derived from case reports. In the past 15 years only two series of pregnant NF patients were reported in English language literature. Neurofibromatosis is a genetic disorder which increases the risk of obstetric complications as well as aggravation of maternal disease. However, here is a case of NF in which transmission to baby has also occurred, which is very rare. How to cite this article Dahiya S, Mukherjee S, Premi HK. Neurofibromatosis in Pregnancy. Int J Adv Integ Med Sci 2016; 1(2):91-92.

scholarly journals Metformin in Pregnancy Study (MiPS): protocol for a systematic review with individual patient data meta-analysis

BMJ Open ◽  
2020 ◽  
Vol 10 (5) ◽  
pp. e036981
Author(s):  
Aya Mousa ◽  
Tone Løvvik ◽  
Ijäs Hilkka ◽  
Sven M Carlsen ◽  
Laure Morin-Papunen ◽  
...  
Keyword(s):  
Individual Patient Data ◽  
Data Extraction ◽  
Meta Analysis ◽  
A Priori ◽  
Patient Data ◽  
Sensitivity Analyses ◽  
Efficacy And Safety ◽  
Adverse Pregnancy ◽  
The Impact ◽  
In Pregnancy

IntroductionGestational diabetes mellitus (GDM) is a common disorder of pregnancy and contributes to adverse pregnancy outcomes. Metformin is often used for the prevention and management of GDM; however, its use in pregnancy continues to be debated. The Metformin in Pregnancy Study aims to use individual patient data (IPD) meta-analysis to clarify the efficacy and safety of metformin use in pregnancy and to identify relevant knowledge gaps.Methods and analysisMEDLINE, EMBASE and all Evidence-Based Medicine will be systematically searched for randomised controlled trials (RCT) testing the efficacy of metformin compared with placebo, usual care or other interventions in pregnant women. Two independent reviewers will assess eligibility using prespecified criteria and will conduct data extraction and quality appraisal of eligible studies. Authors of included trials will be contacted and asked to contribute IPD. Primary outcomes include maternal glycaemic parameters and GDM, as well as neonatal hypoglycaemia, anthropometry and gestational age at delivery. Other adverse maternal, birth and neonatal outcomes will be assessed as secondary outcomes. IPD from these RCTs will be harmonised and a two-step meta-analytic approach will be used to determine the efficacy and safety of metformin in pregnancy, with a priori adjustment for covariates and subgroups to examine effect moderators of treatment outcomes. Sensitivity analyses will assess heterogeneity, risk of bias and the impact of trials which have not provided IPD.Ethics and disseminationAll IPD will be deidentified and studies contributing IPD will have ethical approval from their respective local ethics committees. This study will provide robust evidence regarding the efficacy and safety of metformin use in pregnancy, and may identify subgroups of patients who may benefit most from this treatment modality. Findings will be published in peer-reviewed journals and disseminated at scientific meetings, providing much needed evidence to inform clinical and public health actions in this area.

scholarly journals 531 COVID-19 and Patients with Congenital Heart Disease: Are the Risk Higher? A Systematic Review

2021 ◽  
Vol 108 (Supplement_2) ◽  
Author(s):  
A Haiduc ◽  
M Ogunjimi ◽  
R Shammus ◽  
S Mahmood ◽  
A Harky
Keyword(s):  
Systematic Review ◽  
Case Reports ◽  
Data Extraction ◽  
Meta Analysis ◽  
Case Series ◽  
Future Research ◽  
Extensive Literature ◽  
Mesh Terms ◽  
Extensive Literature Search ◽  
Poor Outcomes

Abstract Introduction We aimed to determine if patients with CHD are at a higher risk of poor outcomes if they have COVID-19, compared to those without CHD. Method A systematic review was executed using the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines. To identify articles related to COVID-19 and CHD, an extensive literature search was performed on EMBASE, Medline, Scopus and Global Health databases using keywords and MeSH terms. Results 12 articles met the inclusion criteria and were included for analysis in this systematic review. Two themes were identified for data extraction: [1] evidence supporting higher risks in CHD patients and [2] evidence against higher risks in CHD patients. After combining the data, there were 99 patients with CHDs out of which 12 required admission to ICU. Conclusions This systematic review suggests that CHD may increase the risk of poor outcomes for those with COVID-19, but also highlights the necessity for more research with larger sample sizes in order to make a more justified conclusion, as the majority of papers that were analysed were case series and case reports. Future research should aim to quantify the risks if possible while accounting for various confounding factors such as age and treatment history.

Probiotics for Clostridium difficile–Associated Diarrhea: Focus on Lactobacillus rhamnosus GG and Saccharomyces boulardii

2007 ◽  
Vol 41 (7-8) ◽  
pp. 1212-1221 ◽  
Author(s):  
Marisel Segarra-Newnham
Keyword(s):  
Clostridium Difficile ◽  
Case Reports ◽  
Data Extraction ◽  
Meta Analysis ◽  
Lactobacillus Rhamnosus ◽  
Case Series ◽  
Saccharomyces Boulardii ◽  
First Episode ◽  
Lactobacillus Rhamnosus Gg ◽  
Clostridium Difficile Associated Diarrhea

Objective: To review the literature on the use of probiotics to treat or prevent recurrences of Clostridium difficile-associated diarrhea (CDAD) by replacing normal gastric flora. Data Sources: PubMed (1970–March 2007) was searched using the terms probiotics, Clostridium difficile, colitis, diarrhea, prevention, and treatment. Study Selection and Data Extraction: Case reports, case series, and clinical trials describing the use of probiotics in the treatment or prevention of recurrences of CDAD as primary outcome were included. Data Synthesis: A variety of controlled trials, case series, and case reports have evaluated probiotics to treat first or recurrent episodes of CDAD. In addition, a meta-analysis has been conducted to try to determine the rote of probiotics in CDAD. In general, most case series and case reports have shown favorable results with Lactobacillus rhamnosus GG or Saccharomyces boulardii. However, other reports have shown lack of benefit. The meta-analysis showed that these probiotics may be useful in treating or preventing recurrences of CDAD. Nonetheless, the heterogeneity of the studies makes definite conclusions difficult. In addition, several cases of bacteremia or fungemia associated with probiotic use have been reported, particularly in the last decade. Patients most commonly affected by these complications are immunosuppressed. Unfortunately, these are also the patients more likely to have severe CDAD or are at risk for recurrences. Conclusions: Additional experience with and study of probiotics are warranted due to numerous unanswered questions. Given the potential for complications in debilitated and immunosuppressed patients, the risks may outweigh benefits, and rational antibiotic use may be a better option to prevent a first episode or recurrence of CDAD.

Sign in / Sign up

Export Citation Format

Share Document