Implementing a comprehensive translational oncology platform: from molecular testing to actionability

Objective: To describe clinical characteristics and outcomes of laboratory-confirmed influenza in hospitalized children in a tertiary care center and to identify factors associated with the severity. Materials and Methods: The present study was a retrospective medical chart review study conducted at King Chulalongkorn Memorial Hospital, Bangkok, Thailand. Data were extracted from children aged under 15 years old hospitalized between January 2014 and December 2018. Patients who had laboratory-confirmed influenza by rapid antigen detection or molecular testing were included. Severe influenza was defined as patients who developed influenza complications or duration of hospitalization for more than three days. Multivariate logistic regression was used to identify the associated factors with the severity of the disease. Results: Three hundred fifty-seven influenza patients were included with median age of 43 months (IQR 19 to 81), of which 63.3% were aged under 60 months. There were 174 patients (48.7%) with comorbidities, most common were immunosuppression (18.2%), chronic pulmonary disease (12.2%), and congenital heart disease (11.5%). Fifty-seven out of 183 patients (31.1%) had history of influenza vaccination in the medical records. One hundred sixty-one patients (45.1%) had 212 influenza complications including influenza-related pneumonia (89, 24.9%), secondary bacterial infection (53, 14.8%), and neurologic complications (47, 13.2%), in which 27 cases (7.6%) were transferred to intensive care unit (ICU). Four cases (1.1%) died but not directly related to influenza. Associated factors with complicated influenza were aged less than 24 months [aOR 2.67 (95% CI 1.68 to 4.26)] and presence of chronic lung disease [aOR 4.34 [95% CI 2.01 to 9.35)]. Conclusion: Two-third of the children hospitalized with influenza were younger than 60 months. Nearly half developed complications most associated with the age of less than two years old and patients with chronic lung disease. Low rates of vaccination were demonstrated. Keywords: Influenza, Pediatrics, Complications, Pneumonia, Hospitalization

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Making sense of rapid antigen testing in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) diagnostics

Diagnosis ◽

10.1515/dx-2020-0131 ◽

2020 ◽

Vol 0 (0) ◽

Author(s):

Camilla Mattiuzzi ◽

Brandon M. Henry ◽

Giuseppe Lippi

Keyword(s):

Severe Acute Respiratory Syndrome ◽

Point Of Care ◽

Turnaround Time ◽

Molecular Testing ◽

Upper Respiratory Tract ◽

Making Sense ◽

Skilled Personnel ◽

Potential Benefits ◽

Antigen Testing ◽

Care Availability

AbstractAlthough the most effective strategy for preventing or containing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreaks relies on early diagnosis, the paramount and unprecedented number of tests needed to fully achieve this target is overwhelming worldwide testing supply and capacity. Molecular detection of SARS-CoV-2 RNA in nasopharyngeal swabs is still considered the reference diagnostic approach. Nonetheless, identification of SARS-CoV-2 proteins in upper respiratory tract specimens and/or saliva by means of rapid (antigen) immunoassays is emerging as a promising screening approach. These tests have some advantages compared to molecular analysis, such as point of care availability, no need of skilled personnel and dedicated instrumentation, lower costs and short turnaround time. However, these advantages are counterbalanced by lower diagnostic sensitivity compared to molecular testing, which would only enable to identifying patients with higher SARS-CoV-2 viral load. The evidence accumulated to-date has hence persuaded us to develop a tentative algorithm, which would magnify the potential benefits of rapid antigen testing in SARS-CoV-2 diagnostics.

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Assessing the utility and attitudes toward molecular testing in neuro-oncology: a survey of the Society for Neuro-Oncology members

Neuro-Oncology Practice ◽

10.1093/nop/npab003 ◽

2021 ◽

Author(s):

Shannon Fortin Ensign ◽

Maya Hrachova ◽

Susan Chang ◽

Maciej M Mrugala

Keyword(s):

Online Survey ◽

Clinical Decision Making ◽

Unmet Needs ◽

Practice Patterns ◽

Response Rate ◽

Clinical Decision ◽

Molecular Testing ◽

Newly Diagnosed ◽

Tumor Boards ◽

Oncology Practice

Abstract Background Molecular testing (MT) is utilized in neuro-oncology with increasing frequency. The aim of this study was to determine clinical practice patterns to acquire this information, interpret and utilize MT for patient care, and identify unmet needs in the practical clinical application of MT. Methods We conducted a voluntary online survey of providers within the Society for Neuro-Oncology (SNO) membership database between March and April 2019. Results We received 152 responses out of 2022 SNO members (7.5% of membership). 88.8% of respondents routinely order MT for newly diagnosed gliomas. Of those who do not, testing is preferentially performed in younger patients or those with midline tumors. 82.8% use MT in recurrent gliomas. Other common indications included: metastatic tumors, meningioma, and medulloblastoma. Many providers utilize more than one resource (36.0%), most frequently using in-house (41.8%) over commercially available panels. 78.1% used the results for clinical decision-making, with BRAF, EGFR, ALK, and H3K27 mutations most commonly directing treatment decisions. Approximately, half (48.5%) of respondents have molecular tumor boards at their institutions. Respondents would like to see SNO-endorsed guidelines on MT, organized lists of targeted agents available for specific mutations, a database of targetable mutations and clinical trials, and more educational programs on MT. Conclusion This survey was marked by several limitations including response rate and interpretation of MT. Among respondents, there is routine use of MT in Neuro-Oncology, however, there remains a need for increased guidance for providers to effectively incorporate the expanding genomic data resulting from MT into daily Neuro-Oncology practice.

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The Prognostic and Predictive Role of Somatic BRCA Mutations in Ovarian Cancer: Results from a Multicenter Cohort Study

Diagnostics ◽

10.3390/diagnostics11030565 ◽

2021 ◽

Vol 11 (3) ◽

pp. 565

Author(s):

Angela Toss ◽

Claudia Piombino ◽

Elena Tenedini ◽

Alessandra Bologna ◽

Elisa Gasparini ◽

...

Keyword(s):

Ovarian Cancer ◽

Positive Impact ◽

Progression Free Survival ◽

Molecular Testing ◽

Wild Type ◽

Brca Mutations ◽

Multicenter Cohort Study ◽

Advanced Stages ◽

Predictive Role

Previous research involving epithelial ovarian cancer patients showed that, compared to germline BRCA (gBRCA) mutations, somatic BRCA (sBRCA) mutations present a similar positive impact with regard to overall survival (OS) and platinum and PARP (poly (ADP-ribose) polymerase) inhibitor sensitivity. Nevertheless, molecular testing in these studies did not include copy number variation (CNV) analyses of BRCA genes. The aim of this study was to explore the prognostic and predictive role of sBRCA mutations as compared to gBRCA mutations in patients who were also tested for CNVs. Among the 158 patients included in the study, 17.09% of patients carried a pathogenic or likely pathogenic gBRCA variant and 15.19% of patients presented pathogenetic or likely pathogenic sBRCA variants and/or CNVs. Overall, 81.6% of the patients included in this study were diagnosed with a serous histotype, and 77.2% were in advanced stages. Among women diagnosed in advanced stages, gBRCA patients showed better progression-free survival and OS as compared to sBRCA and wild-type patients, whereas sBRCA patients did not show any advantage in outcome as compared to wild-type patients. In this study, the introduction of CNV analyses increased the detection rate of sBRCA mutations, and the resulting classification among gBRCA, sBRCA and wild-type patients was able to properly stratify the prognosis of OC patients. Particularly, sBRCA mutation patients failed to show any outcome advantage as compared to wild-type patients.

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No evidence of false-negative Plasmodium falciparum rapid diagnostic results in Monrovia, Liberia

Malaria Journal ◽

10.1186/s12936-021-03774-3 ◽

2021 ◽

Vol 20 (1) ◽

Author(s):

Mandella King ◽

Alexander E. George ◽

Pau Cisteró ◽

Christine K. Tarr-Attia ◽

Beatriz Arregui ◽

...

Keyword(s):

Plasmodium Falciparum ◽

False Negative ◽

Malaria Diagnosis ◽

Rapid Diagnostic Tests ◽

Molecular Testing ◽

False Negatives ◽

Gene Deletions ◽

History Of ◽

Catholic Hospital ◽

Or History

Abstract Background Malaria diagnosis in many malaria-endemic countries relies mainly on the use of rapid diagnostic tests (RDTs). The majority of commercial RDTs used in Africa detect the Plasmodium falciparum histidine-rich protein 2 (PfHRP2). pfhrp2/3 gene deletions can therefore lead to false-negative RDT results. This study aimed to evaluate the frequency of PCR-confirmed, false-negative P. falciparum RDT results in Monrovia, Liberia. Methods PfHRP2-based RDT (Paracheck Pf®) and microscopy results from 1038 individuals with fever or history of fever (n = 951) and pregnant women at first antenatal care (ANC) visit (n = 87) enrolled in the Saint Joseph’s Catholic Hospital (Monrovia) from March to July 2019 were used to assess the frequency of false-negative RDT results. True–false negatives were confirmed by detecting the presence of P. falciparum DNA by quantitative PCR in samples from individuals with discrepant RDT and microscopy results. Samples that were positive by 18S rRNA qPCR but negative by PfHRP2-RDT were subjected to multiplex qPCR assay for detection of pfhrp2 and pfhrp3. Results One-hundred and eighty-six (19.6%) and 200 (21.0%) of the 951 febrile participants had a P. falciparum-positive result by RDT and microscopy, respectively. Positivity rate increased with age and the reporting of joint pain, chills and shivers, vomiting and weakness, and decreased with the presence of coughs and nausea. The positivity rate at first ANC visit was 5.7% (n = 5) and 8% (n = 7) by RDT and microscopy, respectively. Out of 207 Plasmodium infections detected by microscopy, 22 (11%) were negative by RDT. qPCR confirmed absence of P. falciparum DNA in the 16 RDT-negative but microscopy-positive samples which were available for molecular testing. Among the 14 samples that were positive by qPCR but negative by RDT and microscopy, 3 only amplified pfldh, and among these 3 all were positive for pfhrp2 and pfhrp3. Conclusion There is no qPCR-confirmed evidence of false-negative RDT results due to pfhrp2/pfhrp3 deletions in this study conducted in Monrovia (Liberia). This indicates that these deletions are not expected to affect the performance of PfHRP2-based RDTs for the diagnosis of malaria in Liberia. Nevertheless, active surveillance for the emergence of PfHRP2 deletions is required.

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