scholarly journals Detection of COPD in a high-risk population: should the diagnostic work-up include bronchodilator reversibility testing?

2015 ◽  
pp. 407 ◽  
Author(s):  
Charlotte Ulrik ◽  
Peter Kjeldgaard ◽  
Ronald Dahl ◽  
Anders Løkke
Keyword(s):  
High Risk ◽  
High Risk Population ◽  
Risk Population ◽  
Diagnostic Work ◽  
Work Up ◽  
Diagnostic Work Up

Flow Cytometric Immunophenotyping in Myelodysplasia: Discovery and Diagnosis

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. SCI-24-SCI-24
Author(s):  
Arjan A Van de Loosdrecht ◽  
Theresia M. Westers
Keyword(s):  
High Risk ◽  
Research Funding ◽  
Severe Dysplasia ◽  
Diagnostic Score ◽  
Flow Cytometric ◽  
Transfusion Requirements ◽  
Diagnostic Work ◽  
Work Up ◽  
Diagnostic Work Up ◽  
Myeloid Progenitors

Abstract Diagnosis of myelodysplastic syndromes (MDS) is based on the integration of results from diagnostic tools. Initial laboratory assessments in patients with suspected MDS comprise analysis of peripheral blood and bone marrow with the gold standard of cytomorphology, conventional cytogenetics and interphase fluorescence-in-situ hybridization (FISH). Single nucleotide polymorphism (SNP) array and next-generation sequencing (NGS) are emerging techniques. The pathological hallmark of MDS is dysplasia. Flow cytometry (FC) can identify aberrancies in antigen expression and differentiation patterns that are indicative of dysplasia. FC is regarded instrumental and now even recommended in the diagnostic work-up of (suspected) MDS, especially when dysplasia by cytomorphology is minimal and cytogenetics shows no (typical) abnormalities. No single FC marker has been identified that is specific for MDS. The WHO-2008 classification recommends the presence of three or more FC aberrancies as highly suggestive for MDS. Minimal requirements to analyze dysplasia by FC have been proposed by the European LeukemiaNet (ELNet) working group (ELNet iMDS-Flow. ELNet recommendations should enable a categorization of FC results in cytopenic patients as "normal", "suggestive of", or “high probability of” MDS. FC as a single technique is not sufficient for the diagnosis of MDS and should be part of an integrated diagnostic work-up. Within the ELNet-iMDS-Flow group, a score based on four cardinal parameters was validated in MDS patients with <5% blasts and non-clonal cytopenic controls. This diagnostic score comprises: a) SSC of granulocytes (reflecting granularity) as ratio to lymphocytes; b) percentage of CD34+ myeloid progenitors of nucleated cells; c) percentage of B cell progenitors within the total CD34+ compartment; and d) expression of CD45 on CD34+ myeloid progenitors as ratio to lymphocytes. An abnormal value for every single parameter is assigned 1 point; MDS is highly suggestive when a score of 2 or more is obtained. Sensitivity of this diagnostic score was 70% and specificity 92%. It was demonstrated that this score also separates distinct subgroups with respect to prognosis within IPSS-R risk groups. Most flow scores mainly incorporate markers that cover the myelomonocytic lineage, e.g. the flow cytometric scoring system (FCSS). The latter separates patients with no and mild-to-moderate dysplasia from those with severe dysplasia. The FCSS has recently been shown to add significantly in separating patients into low or high risk disease in the revised IPSS subgroups. Finally, FCSS originally designed as a prognostic score, but can also be applied as a diagnostic score as combined with the 4-parameter FC diagnostic score to further improve sensitivity and specificity. Flow profiles based on the myelomonocytic lineage may fail to recognize MDS patients that exclusively show erythroid and/or megakaryocytic dysplasia. Analysis of megakaryocytes is hampered by their paucity. Recent advances shows that when adding erythroid markers such as CD71, CD36 and CD117/CD105 may add significantly to the diagnostic score of MDS by FC. Interestingly, aberrancies in the myelomonocytic lineage have been shown in patients with solely erythroid dysplasia with impact on prognosis. In addition, aberrant FC profile of myeloid progenitors has been associated with high transfusion requirements and disease progression as well as with a short duration of response or even lack of response to growth factor and azacitidine treatment. In conclusion, FC is a useful tool in the diagnostic work-up of MDS. Further studies on the value of FC in diagnosis, prognosis and predicting response to treatment are ongoing, as well as correlation of FC results with data obtained by SNP and NGS within prospective multicenter clinical trials in low and high risk MDS. Disclosures Van de Loosdrecht: celgene: Honoraria, Research Funding; alexion: Research Funding.

Results of annual screening of lung cancer with low dose computed tomography in 5,000 high-risk individuals

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 7566-7566
Author(s):  
G. Veronesi ◽  
M. Bellomi ◽  
L. Spaggiari ◽  
G. Pelosi ◽  
A. Sonzogni ◽  
...  
Keyword(s):  
Lung Cancer ◽  
High Risk ◽  
Low Dose ◽  
Pulmonary Nodules ◽  
Lung Cancers ◽  
Annual Screening ◽  
One Year ◽  
Diagnostic Work ◽  
Work Up ◽  
Diagnostic Work Up

7566 Background: Screening detected lung cancers are correlated with good prognosis however most of the reported cases were detected at baseline screening and little is known about the evolution of pulmonary nodules at annual screening. We report the results of the first and second year of a single centre screening trial focusing the attention on the evolution of pulmonary nodules. Methods: The Cosmos trial started in October 2004 and enrolled 5,202 asymptomatic persons at high risk for lung cancer in one year. Between October 2005 and October 2006, the participants of the study, have been recalled to undergo the annual low dose CT. New lesions were treated according to the baseline diagnostic work up protocol. Previously detected lesions grown at annual screening were investigated with repeated low dose CT and/or Pet scan. Surgical biopsy was scheduled in case of Pet positive or growing nodules. Stable lesions were sent to one year follow up. Results: 4,745 out of 5,202 underwent the annual screening (compliance 92%). Recall rate was 10.7% at baseline and 4% at annual screening. Rate of malignant disease was 1.03% at baseline and 0.7% at annual screening. Patients with stage I disease were 68% at baseline and 76% at annual screening. Of the 32 lung cancers diagnosed at annual screening 8 were new nodules, 1 nodules was stable and 23 nodules progressed from the previous year. Among these, 9 nodules were lower than 5 mm at baseline (out of 2,190 subjects = 0.4%) and 14 were larger than 5 mm (out of 560 subjects =2.5%). Conclusions: Screening low dose spiral CT is an effective tool for the early detection of lung cancer. At first annual screening malignancy rate decreased from 1% to 0.7% and stage distribution was more favourable. However the high rate of delayed diagnosis (2.5%) in cases of nodules larger than 5 mm at baseline CT may require a revision of our proposed diagnostic work up protocol to further anticipate detection of these cases. No significant financial relationships to disclose.

scholarly journals Cisplatin +/− rucaparib after preoperative chemotherapy in patients with triple-negative or BRCA mutated breast cancer

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Maitri Kalra ◽  
Yan Tong ◽  
David R. Jones ◽  
Tom Walsh ◽  
Michael A. Danso ◽  
...  
Keyword(s):  
Breast Cancer ◽  
High Risk ◽  
Neoadjuvant Therapy ◽  
Triple Negative ◽  
Residual Disease ◽  
Disease Free Survival ◽  
Parp Inhibition ◽  
High Risk Population ◽  
Risk Population ◽  
The Impact

AbstractPatients with triple-negative breast cancer (TNBC) who have residual disease after neoadjuvant therapy have a high risk of recurrence. We tested the impact of DNA-damaging chemotherapy alone or with PARP inhibition in this high-risk population. Patients with TNBC or deleterious BRCA mutation (TNBC/BRCAmut) who had >2 cm of invasive disease in the breast or persistent lymph node (LN) involvement after neoadjuvant therapy were assigned 1:1 to cisplatin alone or with rucaparib. Germline mutations were identified with BROCA analysis. The primary endpoint was 2-year disease-free survival (DFS) with 80% power to detect an HR 0.5. From Feb 2010 to May 2013, 128 patients were enrolled. Median tumor size at surgery was 1.9 cm (0–11.5 cm) with 1 (0–38) involved LN; median Residual Cancer Burden (RCB) score was 2.6. Six patients had known deleterious BRCA1 or BRCA2 mutations at study entry, but BROCA identified deleterious mutations in 22% of patients with available samples. Toxicity was similar in both arms. Despite frequent dose reductions (21% of patients) and delays (43.8% of patients), 73% of patients completed planned cisplatin. Rucaparib exposure was limited with median concentration 275 (82–4694) ng/mL post-infusion on day 3. The addition of rucaparib to cisplatin did not increase 2-year DFS (54.2% cisplatin vs. 64.1% cisplatin + rucaparib; P = 0.29). In the high-risk post preoperative TNBC/BRCAmut setting, the addition of low-dose rucaparib did not improve 2-year DFS or increase the toxicity of cisplatin. Genetic testing was underutilized in this high-risk population.

scholarly journals Stroke masquerading as cardiac arrest: the artery of Percheron

2021 ◽  
Vol 14 (1) ◽  
pp. e238681
Author(s):  
Megan Quetsch ◽  
Sureshkumar Nagiah ◽  
Stephen Hedger
Keyword(s):  
Cardiac Arrest ◽  
Clinical Assessment ◽  
Altered Consciousness ◽  
Cognitive Changes ◽  
Consciousness Level ◽  
Artery Of Percheron ◽  
Conscious Level ◽  
Diagnostic Work ◽  
Work Up ◽  
Diagnostic Work Up

The artery of Percheron (AOP) is a rare arterial variant of the thalamic blood supply. Due to the densely packed collection of nuclei it supplies, an infarction of the AOP can be devastating. Here we highlight a patient who had an AOP stroke in the community, which was initially managed as cardiac arrest. AOP strokes most often present with vague symptoms such as reduced conscious level, cognitive changes and confusion without obvious focal neurology, and therefore are often missed at the initial clinical assessment. This case highlights the importance of recognising an AOP stroke as a cause of otherwise unexplained altered consciousness level and the use of MRI early in the diagnostic work-up.

scholarly journals Death of unknown cause? Post-mortem diagnosis of fulminant course of an EBV-associated secondary hemophagocytic lymphohistiocytosis

2021 ◽  
Author(s):  
Josia Fauser ◽  
Stefan Köck ◽  
Eberhard Gunsilius ◽  
Andreas Chott ◽  
Andreas Peer ◽  
...  
Keyword(s):  
Immune Response ◽  
Case Report ◽  
Macrophage Activation ◽  
Post Mortem ◽  
Life Threatening ◽  
Appropriate Therapy ◽  
Diagnostic Work ◽  
Work Up ◽  
Diagnostic Work Up ◽  
Secondary Hemophagocytic Lymphohistiocytosis

SummaryHLH is a life-threatening disease, which is characterized by a dysregulated immune response with uncontrolled T cell and macrophage activation. The often fulminant course of the disease needs a fast diagnostic work-up to initiate as soon as possible the appropriate therapy. We present herein the case of a 71-year-old patient with rapidly progressive hyperinflammatory syndrome, which post mortem resulted in the diagnosis of EBV-associated HLH. With this case report, we intend to highlight the relevance of the HScore in the diagnosis of HLH, to create a greater awareness for EBV as a trigger of HLH, and to demonstrate the importance of treating EBV-associated HLH as early as possible.

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