scholarly journals Systematic Review of Cysteine-Sparing NOTCH3 Missense Mutations in Patients with Clinical Suspicion of CADASIL

2020 ◽  
Author(s):  
Elena Muiño ◽  
Cristina Gallego-Fabrega ◽  
Natalia Cullell ◽  
Caty Carrera ◽  
Nuria Torres ◽  
...  
Keyword(s):  
Systematic Review ◽  
Clinical Suspicion ◽  
Missense Mutations

scholarly journals Systematic Review of Cysteine-Sparing NOTCH3 Missense Mutations in Patients with Clinical Suspicion of CADASIL

2017 ◽  
Vol 18 (9) ◽  
pp. 1964 ◽  
Author(s):  
Elena Muiño ◽  
Cristina Gallego-Fabrega ◽  
Natalia Cullell ◽  
Caty Carrera ◽  
Nuria Torres ◽  
...  
Keyword(s):  
Systematic Review ◽  
Clinical Suspicion ◽  
Missense Mutations

P0051NOVEL AND KNOWN MUTATIONS IDENTIFIED BY CLINICAL EXOME SEQUENCING FOR THE DIAGNOSIS OF POLYCYSTIC KIDNEY DISEASE

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Tiziana Vaisitti ◽  
Monica Sorbini ◽  
Martina Callegari ◽  
Silvia Kalantari ◽  
Valeria Bracciamà ◽  
...  
Keyword(s):  
Family History ◽  
Exome Sequencing ◽  
Autosomal Recessive ◽  
Positive Family History ◽  
Genetic Diagnosis ◽  
Clinical Suspicion ◽  
University Hospital ◽  
Missense Mutations ◽  
Variants Of Unknown Significance ◽  
Clinical Exome Sequencing

Abstract Background and Aims Autosomal dominant PKD determines formation of multiple cysts predominantly in the kidneys and usually becomes symptomatic during adulthood and can lead to renal failure. In contrast, in autosomal recessive PKD cysts occur in both the kidneys and the liver and usually presents an earlier onset. Obtaining genetic diagnosis is important to confirm clinical diagnosis and is required before treating with vasopressin 2 receptor blockers, which are the only drugs known to slow down the disease. Furthermore, in the case of kidney transplant from a living family member it is essential to exclude the presence of the mutation in the donor. We used clinical exome sequencing to provide genetic diagnosis to a cohort of patients with a clinical suspicion of PKD. Method 175 patients were referred to the Immunogenetics and Transplant Biology Service of the Turin University Hospital through a network of nephrology centers operating in the Piedmont region. Some patients were referred following genetic counseling. All patients signed an informed consent and the referring physicians provided relevant clinical data. DNA from eligible patients was extracted, checked for integrity, quantified and used for library preparation. A clinical exome sequencing (CES) kit by Illumina was used, allowing the analysis of 6,700 clinically relevant genes. Results Out of the 175 recruited patients eligible for CES, 38 (21.7%) had a clinical suspicion or diagnosis of PKD, with 50% of them presenting family history. The majority of the cohort was represented by male subjects (60.5%) and included both children (34.2%) and adults. The analytical approach was based on initial analysis of genes responsible for PKD (PKD1, PKD2 and PKHD1). If no mutation could be identified, analysis was then extended to a panel of 99 genes responsible for ciliopathies. This approach led to the identification of causative variants in 33/38 (86.8%) of the PKD cohort, while no variant could be identified in 5/38 patients. In 5/33 (15.2%) patients, mutations were inconclusive as found in heterozygosity in genes known to have an autosomal recessive mode of inheritance, while 27/33 (81.8%) were in line with the initial clinical suspicion/diagnosis. Of these, the majority was represented by missense mutations (12), followed by frameshift and nonsense mutations (6 each) and 3 splicing variants. As expected, the majority of mutations were found in PKD1 17/27 (63%), PKD2 3/27 (11.1%) and PKHD1 2/27 (7.4%). In these two latter patients, variants were found as compound heterozygosity. We also found mutations in other genes known to cause cysts, including TSC2 and CPT2. Of note, in 7 patients carrying PKD1 mutations, we found a second variant in PKD1 or PKHD1. Interestingly, when looking at patients characterized by kidney failure but lacking a clinical suspicion at recruitment or diagnosed with other phenotypes (66/175), we found variants in PKD1 and in PKD2 in 11 patients (9 and 2, respectively). Of all identified variants in PKD1, PKD2 and PKHD1 genes, 17.6% were annotated as pathogenic (C5), 41.2% were likely pathogenic (C4) and 41.2% were variants of unknown significance (C3). 19 variants in these genes were not previously reported. All the variants found in genes responsible for PKD were validated and confirmed by Sanger sequencing. Family segregation studies are ongoing. Finally, it is worth mentioning that in a portion of cases (5/38) with clinical and phenotypic features of PKD, supported also by a positive family history, we could not detect mutations in causative genes. These results may be explained by the presence of intronic variants, in line with data reported in literature. Conclusion These results demonstrate that CES may be applied to PKD patients to identify causative variants during their routine diagnostic flow. Furthermore, CES may be a useful tool to detect mutations in PKD-related genes in patients with undiagnosed diseases, considering its rapidly decreasing costs.

scholarly journals F8 gene mutation type and inhibitor development in patients with severe hemophilia A: systematic review and meta-analysis

Blood ◽  
2012 ◽  
Vol 119 (12) ◽  
pp. 2922-2934 ◽  
Author(s):  
Samantha C. Gouw ◽  
H. Marijke van den Berg ◽  
Johannes Oldenburg ◽  
Jan Astermark ◽  
Philip G. de Groot ◽  
...  
Keyword(s):  
Systematic Review ◽  
Gene Mutation ◽  
Hemophilia A ◽  
High Titer ◽  
Meta Analysis ◽  
Gene Mutations ◽  
Secondary Outcome ◽  
Missense Mutations ◽  
Severe Hemophilia ◽  
Inhibitor Development

Abstract This systematic review was designed to provide more precise effect estimates of inhibitor development for the various types of F8 gene mutations in patients with severe hemophilia A. The primary outcome was inhibitor development and the secondary outcome was high-titer-inhibitor development. A systematic literature search was performed to include cohort studies published in peer-reviewed journals with data on inhibitor incidences in the various F8 gene mutation types and a mutation detection rate of at least 80%. Pooled odds ratios (ORs) of inhibitor development for different types of F8 gene mutations were calculated with intron 22 inversion as the reference. Data were included from 30 studies on 5383 patients, including 1029 inhibitor patients. The inhibitor risk in large deletions and nonsense mutations was higher than in intron 22 inversions (pooled OR = 3.6, 95% confidence interval [95% CI], 2.3-5.7 and OR = 1.4, 95% CI, 1.1-1.8, respectively), the risk in intron 1 inversions and splice-site mutations was equal (pooled OR = 0.9; 95% CI, 0.6-1.5 and OR = 1.0; 95% CI, 0.6-1.5), and the risk in small deletions/insertions and missense mutations was lower (pooled OR = 0.5; 95% CI, 0.4-0.6 and OR = 0.3; 95% CI, 0.2-0.4, respectively). The relative risks for developing high titer inhibitors were similar.

scholarly journals LO075: Clinical exam for acute aortic dissection: a systematic review and meta-analysis

CJEM ◽  
2016 ◽  
Vol 18 (S1) ◽  
pp. S56-S56
Author(s):  
R. Ohle ◽  
H. Kareemi ◽  
J.J. Perry
Keyword(s):  
Systematic Review ◽  
Aortic Dissection ◽  
Neurological Deficit ◽  
Acute Aortic Dissection ◽  
Meta Analysis ◽  
Case Series ◽  
Clinical Findings ◽  
Clinical Suspicion ◽  
Clinical Exam ◽  
Meta Analyses

Introduction: Acute aortic dissection (AAD) is difficult to diagnose and if missed carries a significant mortality rate. Our aim was to assess the accuracy of history, physical exam and plain radiographs compared to advanced imaging in the diagnosis of AAD in adults presenting to the ED with a clinical suspicion of AAD. Methods: We conducted a librarian assisted systematic review. Databases searched: Pubmed, Medline, Embase and the Cochrane database from 1968 to January 2016. No restrictions for language were imposed. Studies were reviewed and data extracted by two independent reviewers. AAD was defined by CTA, MRI or TEE Prospective and retrospective studies of patients presenting with a clinical suspicion of AAD were included. Case series were excluded. Studies were combined if low clinical and statistical heterogeonity (I2<30%). Study quality was assessed using the QUADAS tool. Bivariate random effects meta analyses using Revman 5 and SAS 9.3 was performed. Results: We identified 792 records: 61 selected for full text review, 13 included and a further 7 from reference searches. 20 studies with 4721 participants were included (mean QUADAS score 12/14 SD 1.2, Kappa 0.8). Prevalence of AAD ranged from 9.6-76.1% (mean 39.1% SD 17.1%). Mean diagnosis in those without AAD varied between studies with ACS (30.3% SD 30.1%), Anuerysm(12.4% SD 9.8%), Chest wall pain(18.1% SD 13.3%) and PE(7.9% SD 7.85%) being the most common. The clinical findings most suggestive of AAD were, neurological deficit (specificity 94% LR 4.1 [95% CI, 3.1-5.2], I2 0%, n=9), hypotension(specificity 94% LR 2.6 [95% CI 1.6-4.2], I2 0%, n=8), pulse deficit (specificity 92% LR 3.4 [95% CI 1.8-6.4], I2 0%, n=9) and syncope (specificity 92% LR 1.4 [95% CI 1.1-1.8], I2 10%, n=6). The most useful for identifying patients less likely to have AAD were an absence of a widened mediastinum (sensitivity 80% LR 0.3 [95% CI 0.2-0.5], I2 20%, n=13) and an AHA Aortic dissection risk score <1 (n=2 sensitivity 91%,99% LR 0.02,0.22, [95% CI 0.003-0.128, 95%CI 0.2-0.3]). Conclusion: Suspicion for AAD should be raised with syncope, hypotension and pulse or neurological deficit in the appropriate clinical setting. Conversely the absence of a widened mediastinum and a low ADD score decreases likelihood. Clinical exam alone cannot rule out acute aortic dissection but it can help risk stratify for further testing.

scholarly journals Thrombotic complications in 2928 patients with COVID-19 treated in intensive care: a systematic review

2021 ◽  
Vol 51 (3) ◽  
pp. 595-607
Author(s):  
William J. Jenner ◽  
Rahim Kanji ◽  
Saeed Mirsadraee ◽  
Ying X. Gue ◽  
Susanna Price ◽  
...  
Keyword(s):  
Systematic Review ◽  
Intensive Care ◽  
Venous Thrombosis ◽  
Severe Disease ◽  
Duplex Ultrasound ◽  
Clinical Suspicion ◽  
Systematic Screening ◽  
Patient Demographics ◽  
Included Patient ◽  
Thrombotic Complications

AbstractA prothrombotic state is reported with severe COVID-19 infection, which can manifest in venous and arterial thrombotic events. Coagulopathy is reflective of more severe disease and anticoagulant thromboprophylaxis is recommended in hospitalized patients. However, the prevalence of thrombosis on the intensive care unit (ICU) remains unclear, including whether this is sufficiently addressed by conventional anticoagulant thromboprophylaxis. We aimed to identify the rate of thrombotic complications in ICU-treated patients with COVID-19, to inform recommendations for diagnosis and management. A systematic review was conducted to assess the incidence of thrombotic complications in ICU-treated patients with COVID-19. Observational studies and registries reporting thrombotic complications in ICU-treated patients were included. Information extracted included patient demographics, use of thromboprophylaxis or anticoagulation, method of identifying thrombotic complications, and reported patient outcomes. In 28 studies including 2928 patients, thrombotic complications occurred in 34% of ICU-managed patients, with deep venous thrombosis reported in 16.1% and pulmonary embolism in 12.6% of patients, despite anticoagulant thromboprophylaxis, and were associated with high mortality. Studies adopting systematic screening for venous thrombosis with Duplex ultrasound reported a significantly higher incidence of venous thrombosis compared to those relying on clinical suspicion (56.3% vs. 11.0%, p < 0.001). Despite thromboprophylaxis, there is a very high incidence of thrombotic complications in patients with COVID-19 on the ICU. Systematic screening identifies many thrombotic complications that would be missed by relying on clinical suspicion and should be employed, with consideration given to increased dose anticoagulant thromboprophylaxis, whilst awaiting results of prospective trials of anticoagulation in this cohort.

scholarly journals Pulmonary Embolism Does Not Have an Unusually High Incidence Among Hospitalized COVID19 Patients

2021 ◽  
Vol 27 ◽  
pp. 107602962199647
Author(s):  
Nicolas Gallastegui ◽  
Jenny Y. Zhou ◽  
Annette von Drygalski ◽  
Richard F. W. Barnes ◽  
Timothy M. Fernandes ◽  
...  
Keyword(s):  
Systematic Review ◽  
Pulmonary Embolism ◽  
Clinical Trials ◽  
Case Series ◽  
Clinical Suspicion ◽  
Sample Sizes ◽  
Respiratory Illnesses ◽  
High Incidence ◽  
Hospital Wards ◽  
Larger Sample

Introduction: Acute respiratory illnesses from COVID19 infection are increasing globally. Reports from earlier in the pandemic suggested that patients hospitalized for COVID19 are at particularly high risk for pulmonary embolism (PE). To estimate the incidences of PE during hospitalization for COVID19, we performed a rigorous systematic review of published literature. Methods: We searched for case series, cohort studies and clinical trials from December 1, 2019 to July 13, 2020 that reported the incidence of PE among consecutive patients who were hospitalized for COVID19 in ICUs and in non-ICU hospital wards. To reflect the general population of hospitalized COVID19 patients, we excluded studies in which subject enrollment was linked to the clinical suspicion for venous thromboembolism (VTE). Results: Fifty-seven studies were included in the analysis. The combined random effects estimate of PE incidence among all hospitalized COVID19 patients was 7.1% (95% CI: 5.2%, 9.1%). Studies with larger sample sizes reported significantly lower PE incidences than smaller studies (r2 = 0.161, p = 0.036). The PE incidence among studies that included 400 or more patients was 3.0% (95% CI: 1.7%, 4.6%). Among COVID19 patients admitted to ICUs, the combined estimated PE incidence was 13.7% (95% CI: 8.0%, 20.6%). The incidence of ICU-related PE also decreased as the study sample sizes increased. The single largest COVID19 ICU study (n = 2215) disclosed a PE incidence of 2.3% (95% CI: 1.7%, 3.0%). Conclusion: PE incidences among hospitalized COVID19 patients are much lower than has been previously postulated based on smaller, often biased study reports. The incidence of “microthrombosis,” leading to occlusion of microscopic blood vessels, remains unknown.

scholarly journals Oculodentodigital Dysplasia: A Case Report and Major Review of the Eye and Ocular Adnexa Features of 295 Reported Cases

2020 ◽  
Vol 2020 ◽  
pp. 1-16
Author(s):  
Virang Kumar ◽  
Natario L. Couser ◽  
Arti Pandya
Keyword(s):  
Systematic Review ◽  
Case Report ◽  
Connexin 43 ◽  
Genetic Disorder ◽  
Extensive Literature ◽  
Missense Mutations ◽  
Multiple Congenital Anomalies ◽  
Ocular Adnexa ◽  
Major Review ◽  
Oculodentodigital Dysplasia

Oculodentodigital dysplasia (ODDD) is a rare genetic disorder associated with a characteristic craniofacial profile with variable dental, limb, eye, and ocular adnexa abnormalities. We performed an extensive literature review to highlight key eye features in patients with ODDD and report a new case of a female patient with a heterozygous missense GJA1 mutation (c.65G>A, p.G22E) and clinical features consistent with the condition. Our patient presented with multiple congenital anomalies including syndactyly, microphthalmia, microcornea, retrognathia, and a small nose with hypoplastic alae and prominent columella; in addition, an omphalocele defect was present, which has not been reported in previous cases. A systematic review of the published cases to date revealed 91 literature reports of 295 individuals with ODDD. There were 73 different GJA1 mutations associated with these cases, of which the most common were the following missense mutations: c.605G>A (p.R202H) (11%), c.389T>C (p.I130T) (10%), and c.119C>T (p.A40V) (10%). Mutations most commonly affect the extracellular-1 and cytoplasmic-1 domains of connexin-43 (gene product of GJA1), predominately manifesting in microphthalmia and microcornea. The syndrome appears with an approximately equal sex ratio. The most common eye features reported among all mutations were microcornea, microphthalmia, short palpebral fissures, and glaucoma.

Management of external jugular vein aneurysm: a systematic review

Vascular ◽  
2021 ◽  
pp. 170853812110139
Author(s):  
Petroula Nana ◽  
Eleni Gkrinia ◽  
Chara Maiou ◽  
Ourania Karyda ◽  
Christos Korais ◽  
...  
Keyword(s):  
Systematic Review ◽  
Jugular Vein ◽  
Valsalva Maneuver ◽  
Case Reports ◽  
Case Series ◽  
External Jugular Vein ◽  
Clinical Suspicion ◽  
Histological Evaluation ◽  
Primary Indication ◽  
High Clinical Suspicion

Introduction Aneurysms of the jugular vein system are rare and high clinical suspicion is needed for diagnosis. External jugular vein aneurysms (EJVA) are considered innocent lesions that need treatment mainly for aesthetic reasons. The aim of this systematic review was to present current literature regarding diagnosis and management of EJVAs. Methods A literature review was conducted through the Pubmed/Medline and Scopus regarding articles referring on EJVA from 2000 to 2020. Using the PRISMA guidelines (Preferred Reporting Items for Systematic reviews and Meta-Analyses), 30 articles were identified, according to inclusion criteria. Demographics, clinical characteristics, etiology, diagnostic imaging, complications, treatment, and histopathological findings were recorded and analyzed. Results Twenty-seven case reports and one case series were identified, including 30 patients and 31 EJVAs. One-third of patients (30.3%) were < 18 years old (mean age 32 years, range 1–72 years) and 54% of them were females. In 51% of the cases, the lesion was characterized as a true aneurysm after histological evaluation. The presence of a soft cervical mass was the most common clinical symptom, while Valsalva maneuver pointed out the presence of an EJVA in 66.7% of patients. Diagnosis was achieved using ultrasonography, computed tomography, or magnetic resonance imaging. Forty-three percent of the patients underwent more than one radiological examination. Twenty patients underwent surgical management. The primary indication of surgical treatment was aesthetic reasons (11/20, 55%). Thrombosis was the most common EJVA complication (11/30, 36.3%). Conclusions Differential diagnosis of neck mass should include EJVA. High clinical suspicion and adequate imaging are important for diagnosis. Open surgical approach is the more commonly applied therapeutic strategy.

scholarly journals Features of Autosomal Recessive Alport Syndrome: A Systematic Review

2019 ◽  
Vol 8 (2) ◽  
pp. 178 ◽  
Author(s):  
Jiwon Lee ◽  
Kandai Nozu ◽  
Dae Choi ◽  
Hee Kang ◽  
II-Soo Ha ◽  
...  
Keyword(s):  
Systematic Review ◽  
Alport Syndrome ◽  
Autosomal Recessive ◽  
Autosomal Recessive Inheritance ◽  
Missense Mutations ◽  
Lower Prevalence ◽  
Delayed Onset ◽  
Extrarenal Manifestations ◽  
Stage Renal Disease ◽  
End Stage

Alport syndrome (AS) is one of the most frequent hereditary nephritis leading to end-stage renal disease (ESRD). Although X-linked (XLAS) inheritance is the most common form, cases with autosomal recessive inheritance with mutations in COL4A3 or COL4A4 are being increasingly recognized. A systematic review was conducted on autosomal recessive Alport syndrome (ARAS). Electronic databases were searched using related terms (until Oct 10th, 2018). From 1601 articles searched, there were 26 eligible studies with 148 patients. Female and male patients were equally affected. About 62% of patients had ESRD, 64% had sensorineural hearing loss (SNHL) and 17% had ocular manifestation. The median at onset was 2.5 years for hematuria (HU), 21 years for ESRD, and 13 years for SNHL. Patients without missense mutations had more severe outcomes at earlier ages, while those who had one or two missense mutations had delayed onset and lower prevalence of extrarenal manifestations. Of 49 patients with kidney biopsy available for electron microscopy (EM) pathology, 42 (86%) had typical glomerular basement membrane (GBM) changes, while 5 (10%) patients showed GBM thinning only. SNHL developed earlier than previously reported. There was a genotype phenotype correlation according to the number of missense mutations. Patients with missense mutations had delayed onset of hematuria, ESRD, and SNHL and lower prevalence of extrarenal manifestations.

scholarly journals Distribution, prevalence, and causative agents of fungal keratitis: A systematic review and meta-analysis (1990 to 2020)

2021 ◽  
Author(s):  
Kazem Ahmadikia ◽  
Sanaz Aghaei Gharehbolagh ◽  
Bahareh Fallah ◽  
Mahsa Naeimi ◽  
Pooneh Malekifar ◽  
...  
Keyword(s):  
Systematic Review ◽  
Fusarium Species ◽  
Meta Analysis ◽  
Distinct Species ◽  
Fungal Keratitis ◽  
Clinical Suspicion ◽  
Pooled Prevalence ◽  
Common Causes ◽  
Causative Agents ◽  
Patient Groups

AbstractFungal keratitis is a sight-threatening infection with global distribution. In this systematic review and meta-analysis we collected all the articles with data on the prevalence of fungal keratitis among various patient groups from January 1, 1990 to May 27, 2020. The 169 eligible articles were divided into 6 groups. The pooled prevalence was variable with values ranging from 0.05% among post-keratoplasty patients to 43.01% among patients with a clinical suspicion of fungal keratitis. Except for post-keratoplasty cases (yeast: 51.80%), in all patient groups moulds were more common than yeasts. Although more than 50 distinct species of fungi have been found to cause fungal keratitis, Fusarium species followed by Aspergillus species were the most common causes of the disease. In general, 9.29% (95% CI 6.52, 12.38) of fungal keratitis cases were mixed with bacterial agents.

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