scholarly journals Discrepant molecular and clinical diagnoses in Beckwith-Wiedemann and Silver-Russell syndromes

2019 ◽  
Vol 101 ◽  
Author(s):  
Deborah J.G. Mackay ◽  
Jet Bliek ◽  
Maria Paola Lombardi ◽  
Silvia Russo ◽  
Luciano Calzari ◽  
...  
Keyword(s):  
Clinical Diagnosis ◽  
Accurate Diagnosis ◽  
Molecular Testing ◽  
Clinical Heterogeneity ◽  
Imprinting Disorders ◽  
Molecular Alterations ◽  
Clinical Diagnoses ◽  
Silver Russell Syndrome

AbstractBeckwith-Wiedemann syndrome (BWS) and Silver-Russell syndrome (SRS) are two imprinting disorders associated with opposite molecular alterations in the 11p15.5 imprinting centres. Their clinical diagnosis is confirmed by molecular testing in 50–70% of patients. The authors from different reference centres for BWS and SRS have identified single patients with unexpected and even contradictory molecular findings in respect to the clinical diagnosis. These patients clinically do not fit the characteristic phenotypes of SRS or BWS, but illustrate their clinical heterogeneity. Thus, comprehensive molecular testing is essential for accurate diagnosis and appropriate management, to avoid premature clinical diagnosis and anxiety for the families.

scholarly journals One test for all: whole exome sequencing significantly improves the diagnostic yield in growth retarded patients referred for molecular testing for Silver–Russell syndrome

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Robert Meyer ◽  
Matthias Begemann ◽  
Christian Thomas Hübner ◽  
Daniela Dey ◽  
Alma Kuechler ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Diagnostic Yield ◽  
Uniparental Disomy ◽  
Molecular Testing ◽  
Main Body ◽  
Comprehensive Overview ◽  
Maternal Uniparental Disomy ◽  
Whole Exome ◽  
Silver Russell Syndrome

Abstract Background Silver-Russell syndrome (SRS) is an imprinting disorder which is characterised by severe primordial growth retardation, relative macrocephaly and a typical facial gestalt. The clinical heterogeneity of SRS is reflected by a broad spectrum of molecular changes with hypomethylation in 11p15 and maternal uniparental disomy of chromosome 7 (upd(7)mat) as the most frequent findings. Monogenetic causes are rare, but a clinical overlap with numerous other disorders has been reported. However, a comprehensive overview on the contribution of mutations in differential diagnostic genes to phenotypes reminiscent to SRS is missing due to the lack of appropriate tests. With the implementation of next generation sequencing (NGS) tools this limitation can now be circumvented. Main body We analysed 75 patients referred for molecular testing for SRS by a NGS-based multigene panel, whole exome sequencing (WES), and trio-based WES. In 21/75 patients a disease-causing variant could be identified among them variants in known SRS genes (IGF2, PLAG1, HMGA2). Several patients carried variants in genes which have not yet been considered as differential diagnoses of SRS. Conclusions WES approaches significantly increase the diagnostic yield in patients referred for SRS testing. Several of the identified monogenetic disorders have a major impact on clinical management and genetic counseling.

Acute Sinusitis—Principles of Judicious Use of Antimicrobial Agents

PEDIATRICS ◽  
1998 ◽  
Vol 101 (Supplement_1) ◽  
pp. 174-177 ◽  
Author(s):  
Katherine L. O'Brien ◽  
Scott F. Dowell ◽  
Benjamin Schwartz ◽  
S. Michael Marcy ◽  
William R. Phillips ◽  
...  
Keyword(s):  
Bacterial Infection ◽  
Clinical Diagnosis ◽  
Antimicrobial Agents ◽  
Accurate Diagnosis ◽  
Acute Sinusitis ◽  
Persistent Symptoms ◽  
Published Evidence

Establishing an accurate diagnosis of bacterial sinusitis is challenging but critical, because viral rhinosinusitis is at least 20 to 200 times more common than bacterial infection of the sinuses. Strict criteria for clinical diagnosis that require either prolonged and persistent symptoms or an acute severe presentation are supported with published evidence.

Targeted therapies in cholangiocarcinoma: Assessment of US oncologist practice patterns.

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 347-347
Author(s):  
Kinjal Parikh ◽  
Davecia Ragoonath Cameron ◽  
Tristin Abair ◽  
Patrick Kugel ◽  
Arndt Vogel
Keyword(s):  
Clinical Practice ◽  
Targeted Therapies ◽  
Progressive Disease ◽  
Community Setting ◽  
Molecular Testing ◽  
Learning Needs ◽  
Self Awareness ◽  
Multiple Choice Questions ◽  
Molecular Alterations ◽  
Practice Assessment

347 Background: Chemotherapy is a mainstay treatment modality for patients with advanced cholangiocarcinoma (CCA). Recent developments and new approvals have led to changing paradigms, incorporating the use of targeted therapies for patients with progressive disease. Given the need for a greater understanding of the molecular alterations, varying targets, and available and emerging therapies, education is needed to assess knowledge regarding these recent advances in unresectable CCA. The goal of this activity was to increase the knowledge of self-assess the learning needs of oncologists in treating patients with unresectable CCA. Methods: The education included 25 multiple choice questions in a continuing medical education (CME)-certified clinical practice assessment to assess practice gaps. The questions were designed to measure knowledge, competence, confidence, and attitudes of oncologists regarding clinical evidence, role of molecular testing, and place in the treatment paradigm for targeted therapies in unresectable CCA. The self-assessment was made available online to physicians as a learning tool to gain foundational knowledge, as well as receive feedback about their performance as compared to other test-takers, to improve self-awareness of their own personal educational gaps. The activity launched 6/24/20, and data are reported through 8/31/20. Results: A total of 1,009 learners, including 758 physicians, participated in the activity. Of the 104 oncologists that participated, a majority practiced in the community setting, saw patients with a range of cancers, and were not confident about using targeted therapies or recognizing targets for biomarker testing. Oncologists demonstrated the following gaps related to: NGS sequencing and biomarkers: 21% do not use; 32% use upon progressive disease; 35% did not realize that not all panels detect FGFR2 fusions; 20% do not test for biomarkers; 29% and 56% test for IDH or FGFR, respectively; 60% recognize the incidence of IDH1 mutations; Clinical trial (FIGHT202 and ClarIDHy): 45% were able to identify biomarker eligibility for pemigatinib; 9% were able to identify pemigatinib OS outcomes; 30% were able to recognize most common grade 3 AE of pemigatinib; 51% recognized the PFS endpoint with ivosidenib; 34% were able to identify eligibility for ivosidenib; 55% recognized most common AEs of ivosidenib. Conclusions: This CME-certified clinical practice assessment identified gaps in knowledge, competence, and confidence regarding testing and use of targeted therapies and emerging data in patients with unresectable CCA. As new data emerges and the number of targets and targeted therapies expand, continued education remains important to continue to optimize patient care.

scholarly journals Clinical diagnoses vs. autopsy findings in early deceased septic patients in the intensive care: a retrospective cohort study

2020 ◽  
Author(s):  
Rob G. H. Driessen ◽  
Bartholomeus G. H. Latten ◽  
Dennis C. J. J. Bergmans ◽  
Riquette P. M. G. Hulsewe ◽  
Johanna W. M. Holtkamp ◽  
...  
Keyword(s):  
Intensive Care ◽  
Clinical Diagnosis ◽  
Causes Of Death ◽  
Early Death ◽  
Class I ◽  
Icu Patients ◽  
Icu Admission ◽  
Clinical Diagnoses ◽  
Important Diagnostic Tool ◽  
Record Review

AbstractEarly death in sepsis occurs frequently; however, specific causes are largely unknown. An autopsy can contribute to ascertain causes of death. The objective of the study was to determine discrepancies in clinical diagnosis and postmortem findings in septic intensive care unit (ICU) patients deceased within 48 h after ICU admission. All septic ICU patients who deceased within 48 h after ICU admission were identified and included. Four intensivists determined the clinical cause of death by medical record review. An autopsy was performed within 24 h of death. Clinical diagnosis and postmortem findings were compared and classified as autopsy-identified missed clinical diagnoses and autopsy-refuted diagnoses. Class I and II missed major diagnoses using the Goldman criteria were scored. Between 2012 and 2017, 1107 septic patients were admitted to ICU. Of these, 344 patients (31%) died, of which 97 patients (28%) deceased within 48 h. In 32 (33%) early deceased patients, an autopsy was agreed. There were 26 autopsy-identified missed clinical diagnoses found, mostly myocardial infarction (n = 4) and pneumonia (n = 4). In four patients (13%), a class I discrepancy was found. In fourteen patients (42%), a class II discrepancy was found. In conclusion, an autopsy is an important diagnostic tool that can identify definite causes of death. These diagnoses deviate from diagnoses established during admission in early deceased sepsis patients.

scholarly journals Molecular Neuropathology in Practice: Clinical Profiling and Integrative Analysis of Molecular Alterations in Glioblastoma

2019 ◽  
Vol 6 ◽  
pp. 237428951984835 ◽  
Author(s):  
MacLean P. Nasrallah ◽  
Zev A. Binder ◽  
Derek A. Oldridge ◽  
Jianhua Zhao ◽  
David B. Lieberman ◽  
...  
Keyword(s):  
Patient Care ◽  
Dna Methyltransferase ◽  
Improve Patient Care ◽  
Return Of Results ◽  
Molecular Testing ◽  
Methylguanine Dna Methyltransferase ◽  
Molecular Alterations ◽  
Molecular Abnormalities ◽  
Tissue Handling ◽  
Testing Algorithm

Molecular profiling of glioblastoma has revealed complex cytogenetic, epigenetic, and molecular abnormalities that are necessary for diagnosis, prognosis, and treatment. Our neuro-oncology group has developed a data-driven, institutional consensus guideline for efficient and optimal workup of glioblastomas based on our routine performance of molecular testing. We describe our institution’s testing algorithm, assay development, and genetic findings in glioblastoma, to illustrate current practices and challenges in neuropathology related to molecular and genetic testing. We have found that coordination of test requisition, tissue handling, and incorporation of results into the final pathologic diagnosis by the neuropathologist improve patient care. Here, we present analysis of O6-methylguanine-DNA-methyltransferase promoter methylation and next-generation sequencing results of 189 patients, obtained utilizing our internal processes led by the neuropathology team. Our institutional pathway for neuropathologist-driven molecular testing has streamlined the management of glioblastoma samples for efficient return of results for incorporation of genomic data into the pathological diagnosis and optimal patient care.

Primary Lung Cribriform Adenocarcinoma With Squamoid Morules Harboring Somatic CTNNB1 Mutation in a Never-Smoked Healthy Adolescent

2020 ◽  
Vol 23 (6) ◽  
pp. 472-475
Author(s):  
Hao Wu ◽  
Qiqi Ye ◽  
Dana Razzano ◽  
Oya Tugal ◽  
Jeremy Rosenblum ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Congenital Malformation ◽  
Pediatric Patients ◽  
Molecular Testing ◽  
Adolescent Female ◽  
Healthy Adolescent ◽  
Molecular Alterations ◽  
Tissue Of Origin ◽  
Lung Adenocarcinomas ◽  
Ctnnb1 Mutation

Primary lung adenocarcinomas are rare in pediatric patients, and even rarer in patients without precedent malignancy or congenital malformation. Here we present the first reported case of primary lung cribriform adenocarcinoma with squamoid morules in a previously healthy adolescent female. Molecular testing identified CTNNB1 mutation in the tumor and excluded other common mutations in lung adenocarcinoma. Our case suggests molecular alterations to the same signaling pathway can lead to similar histomorphology regardless of the tissue of origin.

scholarly journals Clinical manifestations and imaging features of white matter demyelination in older patients

2020 ◽  
Vol 48 (11) ◽  
pp. 030006052096680
Author(s):  
Jian Li ◽  
Yi-Ming Zhao
Keyword(s):  
White Matter ◽  
Clinical Diagnosis ◽  
Older Patients ◽  
Demyelinating Disease ◽  
Clinical Manifestations ◽  
Imaging Features ◽  
Significant Difference ◽  
Clinical Diagnoses ◽  
Chief Complaints ◽  
Magnetic Resonance Imaging Mri

Objective To investigate the clinical manifestations and imaging features of older patients with white matter demyelination diagnosed by magnetic resonance imaging (MRI). Methods Ninety-six patients with leukoaraiosis diagnosed by MRI were divided by their clinical diagnoses into a demyelinating group (40 cases) and a non-demyelinating group (56 cases). The imaging and clinical features of the patients in the two groups were analyzed. Results Compared with the non-demyelinating group, there were significantly more women in the demyelinating group than men. There was no significant difference in age between the two groups. Of the 37 cases who had an imaging report of “white matter demyelination and multiple sclerosis,” 36 cases had a clinical diagnosis in accordance with white matter demyelination (97.3%). Of the 59 cases who had an imaging report of “white matter demyelination”, only four cases had a clinical diagnosis in accordance with demyelination (6.8%). Conclusion In older patients with headaches, vertigo, other head symptoms, and unilateral numbness as the chief complaints, a clinical diagnosis of demyelinating disease is very unlikely when the imaging report states white matter demyelination only.

Behavioural Analysis: Does It Matter?

1997 ◽  
Vol 25 (3) ◽  
pp. 231-249 ◽  
Author(s):  
Dietmar Schulte
Keyword(s):  
Clinical Diagnosis ◽  
Individual Characteristics ◽  
Individual Therapy ◽  
Integrative Model ◽  
Treatment Programs ◽  
Problem Analysis ◽  
Behaviour Therapy ◽  
General Terms ◽  
Clinical Diagnoses ◽  
Therapy Strategies

Behavioural or, in more general terms, problem analysis is usually regarded as the prerequisite of behaviour therapy. In behaviour therapy research, however, problem analysis does not play a key role. Patients are usually assigned to treatment methods on the basis of clinical diagnosis. It could be assumed that the lack of attention to the patient's individual characteristics should lead to poorer therapy outcome results. However, empirical data of a project reviewed in this paper in fact showed that assigning patients to standard treatment merely on the basis of clinical diagnoses provides results equal to or even better than those of optimized individual therapy strategies. Two premises of problem analysis were therefore tested. It could be shown that therapists would diagnose different problem conditions not only for patients with different types of phobia, but also, as expected, for patients with identical diagnoses. However, this did not—as would be expected according to the second premise of problem analysis—result in choosing different individual therapy strategies. One reason for these findings could be that behaviour therapy research has been able to provide treatment programs that have been differentiated and gradually optimized for specific diagnostic groups. To decide on the application of these treatment programs, clinical diagnoses are necessary. It is suggested that clinical diagnosis and problem analysis should be complementary. An integrative model is suggested.

scholarly journals Prospective Analysis of Scrotal Pathology Referrals – Are Referrals Appropriate and Accurate?

2006 ◽  
Vol 88 (4) ◽  
pp. 363-366 ◽  
Author(s):  
Paul W Foster ◽  
Alastair WS Ritchie ◽  
David J Jones
Keyword(s):  
Primary Care ◽  
Testicular Cancer ◽  
Care Setting ◽  
Primary Care Setting ◽  
Care Physician ◽  
Accurate Diagnosis ◽  
Benign Pathology ◽  
Clinical Diagnoses ◽  
Treatable Condition ◽  
Referral Practice

INTRODUCTION Testicular cancer is a relatively uncommon, treatable condition. A general practitioner would expect to see, on average, one case of testicular cancer in the whole of their career. Benign scrotal conditions are extremely common and the source of many primary care consultations. The main patient expectations of these attendances are accurate diagnosis and adequate re-assurance as often they are the source of much anxiety and perceived embarrassment. The aim of this study was to examine the content and referral practice of primary care referral of testicular pathology and the resultant findings of the specialist practitioner. PATIENTS AND METHODS A total of 201 patients referred with scrotal pathology were prospectively analysed at the time of specialist practitioner assessment by means of data recording in a urological surgery unit and regional peripheral community clinics. RESULTS In the study group, 53 patients were referred under the 2-week rule. Of these, 9 (17%) were found to have testicular cancer. Five (36%) cancers were referred outside the 2-week rule referrals; 1 cancer was missed and 2 diagnoses delayed. In total, 44% of final clinical diagnoses differed between the referring primary care physician and the specialist practitioner. Of the 71 (35%) patients referred with a suspicion of cancer, 62 (87%) were subsequently found to be of clinically benign pathology. Overall, 80% of patients were referred more urgently than the opinion of the specialist practitioner. CONCLUSIONS Scrotal examination in the primary care setting appears to be of variable accuracy. Many patients referred with a high suspicion of cancer are found to have benign pathology. Two-week rule referrals have an acceptable positive predictive value for testicular cancer (17%). Disagreements exist in the referral priority of patients.

Clinical Diagnosis of Classical Cornelia de Lange Syndrome Made From Postmortem Examination of Second Trimester Fetus With Novel NIPBL Pathogenic Variant

2019 ◽  
Vol 22 (5) ◽  
pp. 475-479 ◽  
Author(s):  
Jennifer Hague ◽  
Philip Twiss ◽  
Zoe Mead ◽  
Soo-Mi Park
Keyword(s):  
Clinical Diagnosis ◽  
Upper Limb ◽  
Growth Retardation ◽  
Postmortem Examination ◽  
Pathogenic Variant ◽  
Cornelia De Lange Syndrome ◽  
Molecular Testing ◽  
Intrauterine Death ◽  
Second Trimester ◽  
Cornelia De Lange

Classical Cornelia de Lange syndrome (CdLS) is a rare genetic disorder which is associated with distinctive facial features, growth retardation, significant intellectual disability and global developmental delay, hirsutism, and upper-limb reduction defects. Classical CdLS is associated with pathogenic variants in NIPBL. We present a clinical diagnosis of classical CdLS made in a second trimester male fetus with advanced maceration who had undergone intrauterine death at 15 + 6 weeks gestation. The diagnosis was suspected after multiple congenital anomalies were identified on fetal postmortem examination. These included intrauterine growth retardation, upper limb anomalies, ventricular septal defect and diaphragmatic hernia, and skeletal and genitourinary abnormalities. Related prenatal screening findings included a raised nuchal translucency and low maternal serum pregnancy-associated plasma protein-A. Targeted molecular sequencing of genes associated with CdLS identified a novel de novo frameshift pathogenic variant in NIPBL, which confirmed the diagnosis. This report describes our case and reviews the current literature on prenatal diagnosis of CdLS. In summary, we demonstrate that clinical diagnosis of CdLS in a second trimester fetus, through postmortem examination findings, is possible, with confirmation through molecular testing.

Sign in / Sign up

Export Citation Format

Share Document