Are Molecular Tests Necessary to Diagnose NIFTP?

Abstract. Tuberculosis (TB) remains among the top 10 infectious diseases with highest mortality globally since the 1990s despite effective chemotherapy. Among 10 million patients that fell ill with tuberculosis in the year 2017, 36 % were undiagnosed or detected and not reported; the number goes as high as 55 % in Tanzania, showing that the diagnosis of TB is a big challenge in the developing countries. There have been great advancements in TB diagnostics with introduction of the molecular tests such as Xpert MTB/RIF, loop-mediated isothermal amplification, lipoarabinomannan urine strip test, and molecular line-probe assays. However, most of the hospitals in Tanzania still rely on the TB score chart in children, the WHO screening questions in adults, acid-fast bacilli and chest x-ray for the diagnosis of TB. Xpert MTB/RIF has been rolled-out but remains a challenge in settings where the samples for testing must be transported over many kilometers. Imaging by sonography – nowadays widely available even in rural settings of Tanzania – has been shown to be a useful tool in the diagnosis of extrapulmonary tuberculosis. Despite all the efforts and new diagnostics, 30–50 % of patients in high-burden TB countries are still empirically treated for tuberculosis. More efforts need to be placed if we are to reduce the death toll by 90 % until 2030.

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Bilateral Phyllodes Giant Tumor. A Case Report Analyzed by Array-CGH

Diagnostics ◽

10.3390/diagnostics10100825 ◽

2020 ◽

Vol 10 (10) ◽

pp. 825

Author(s):

Francesco Fortarezza ◽

Federica Pezzuto ◽

Gerardo Cazzato ◽

Clelia Punzo ◽

Antonio d’Amati ◽

...

Keyword(s):

Array Cgh ◽

Phyllodes Tumor ◽

Molecular Classification ◽

Left Breast ◽

Comparative Genomic ◽

Fish Analysis ◽

Molecular Tests ◽

Giant Tumor ◽

Metastatic Risk ◽

The Right

The breast phyllodes tumor is a biphasic tumor that accounts for less than of 1% of all breast neoplasms. It is classified as benign, borderline, or malignant, and can mimic benign masses. Some recurrent alterations have been identified. However, a precise molecular classification of these tumors has not yet been established. Herein, we describe a case of a 43-year-old woman that was admitted to the emergency room for a significant bleeding from the breast skin. A voluminous ulcerative mass of the left breast and multiple nodules with micro-calcifications on the right side were detected at a physical examination. A left total mastectomy and a nodulectomy of the right breast was performed. The histological diagnosis of the surgical specimens reported a bilateral giant phyllodes tumor, showing malignant features on the left and borderline characteristics associated with a fibroadenoma on the right. A further molecular analysis was carried out by an array-Comparative Genomic Hybridization (CGH) to characterize copy-number alterations. Many losses were detected in the malignant mass, involving several tumor suppressor genes. These findings could explain the malignant growth and the metastatic risk. In our study, genomic profiling by an array-CGH revealed a greater chromosomal instability in the borderline mass (40 total defects) than in the malignant (19 total defects) giant phyllodes tumor, reflecting the tumor heterogeneity. Should our results be confirmed with more sensitive and specific molecular tests (DNA sequencing and FISH analysis), they could allow a better selection of patients with adverse pathological features, thus optimizing and improving patient’s management.

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A Digital Pathology Solution to Resolve the Tissue Floater Conundrum

Archives of Pathology & Laboratory Medicine ◽

10.5858/arpa.2020-0034-oa ◽

2020 ◽

Author(s):

Liron Pantanowitz ◽

Pamela Michelow ◽

Scott Hazelhurst ◽

Shivam Kalra ◽

Charles Choi ◽

...

Keyword(s):

Digital Pathology ◽

Primary Diagnosis ◽

Image Search ◽

Molecular Tests ◽

Tissue Identification ◽

Digital Database ◽

Glass Slides ◽

Search Tool ◽

Hematoxylin And Eosin ◽

Whole Slide Images

Context.— Pathologists may encounter extraneous pieces of tissue (tissue floaters) on glass slides because of specimen cross-contamination. Troubleshooting this problem, including performing molecular tests for tissue identification if available, is time consuming and often does not satisfactorily resolve the problem. Objective.— To demonstrate the feasibility of using an image search tool to resolve the tissue floater conundrum. Design.— A glass slide was produced containing 2 separate hematoxylin and eosin (H&E)-stained tissue floaters. This fabricated slide was digitized along with the 2 slides containing the original tumors used to create these floaters. These slides were then embedded into a dataset of 2325 whole slide images comprising a wide variety of H&E stained diagnostic entities. Digital slides were broken up into patches and the patch features converted into barcodes for indexing and easy retrieval. A deep learning-based image search tool was employed to extract features from patches via barcodes, hence enabling image matching to each tissue floater. Results.— There was a very high likelihood of finding a correct tumor match for the queried tissue floater when searching the digital database. Search results repeatedly yielded a correct match within the top 3 retrieved images. The retrieval accuracy improved when greater proportions of the floater were selected. The time to run a search was completed within several milliseconds. Conclusions.— Using an image search tool offers pathologists an additional method to rapidly resolve the tissue floater conundrum, especially for those laboratories that have transitioned to going fully digital for primary diagnosis.

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Aptamer-Based Diagnostic Systems for the Rapid Screening of TB at the Point-of-Care

Diagnostics ◽

10.3390/diagnostics11081352 ◽

2021 ◽

Vol 11 (8) ◽

pp. 1352

Author(s):

Darius Riziki Martin ◽

Nicole Remaliah Sibuyi ◽

Phumuzile Dube ◽

Adewale Oluwaseun Fadaka ◽

Ruben Cloete ◽

...

Keyword(s):

Low Income ◽

Point Of Care ◽

Health Care Systems ◽

Cost Effective ◽

Rapid Screening ◽

Low Income Countries ◽

Sputum Smear ◽

Diagnostic Systems ◽

Molecular Tests ◽

Rapid Tests

The transmission of Tuberculosis (TB) is very rapid and the burden it places on health care systems is felt globally. The effective management and prevention of this disease requires that it is detected early. Current TB diagnostic approaches, such as the culture, sputum smear, skin tuberculin, and molecular tests are time-consuming, and some are unaffordable for low-income countries. Rapid tests for disease biomarker detection are mostly based on immunological assays that use antibodies which are costly to produce, have low sensitivity and stability. Aptamers can replace antibodies in these diagnostic tests for the development of new rapid tests that are more cost effective; more stable at high temperatures and therefore have a better shelf life; do not have batch-to-batch variations, and thus more consistently bind to a specific target with similar or higher specificity and selectivity and are therefore more reliable. Advancements in TB research, in particular the application of proteomics to identify TB specific biomarkers, led to the identification of a number of biomarker proteins, that can be used to develop aptamer-based diagnostic assays able to screen individuals at the point-of-care (POC) more efficiently in resource-limited settings.

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The interplay of Clostridioides difficile infection and inflammatory bowel disease

Therapeutic Advances in Gastroenterology ◽

10.1177/17562848211020285 ◽

2021 ◽

Vol 14 ◽

pp. 175628482110202

Author(s):

Kanika Sehgal ◽

Devvrat Yadav ◽

Sahil Khanna

Keyword(s):

Inflammatory Bowel Disease ◽

Bowel Disease ◽

Adverse Outcomes ◽

Molecular Tests ◽

Clostridioides Difficile ◽

Increased Risk ◽

Clostridioides Difficile Infection ◽

Pros And Cons ◽

Inflammatory Bowel ◽

High Index Of Suspicion

Inflammatory bowel disease (IBD) is a chronic disease of the intestinal tract that commonly presents with diarrhea. Clostridioides difficile infection (CDI) is one of the most common complications associated with IBD that lead to flare-ups of underlying IBD. The pathophysiology of CDI includes perturbations of the gut microbiota, which makes IBD a risk factor due to the gut microbial alterations that occur in IBD, predisposing patients CDI even in the absence of antibiotics. Superimposed CDI not only worsens IBD symptoms but also leads to adverse outcomes, including treatment failure and an increased risk of hospitalization, surgery, and mortality. Due to the overlapping symptoms and concerns with false-positive molecular tests for CDI, diagnosing CDI in patients with IBD remains a clinical challenge. It is crucial to have a high index of suspicion for CDI in patients who seem to be experiencing an exacerbation of IBD symptoms. Vancomycin and fidaxomicin are the first-line treatments for the management of CDI in IBD. Microbiota restoration therapies effectively prevent recurrent CDI in IBD patients. Immunosuppression for IBD in IBD patients with CDI should be managed individually, based on a thorough clinical assessment and after weighing the pros and cons of escalation of therapy. This review summarizes the epidemiology, pathophysiology, the diagnosis of CDI in IBD, and outlines the principles of management of both CDI and IBD in IBD patients with CDI.

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What Every Neuropathologist Needs to Know: Practical Aspects and Pitfalls in Molecular Diagnosis of Brain Tumors

Journal of Neuropathology & Experimental Neurology ◽

10.1093/jnen/nlab033 ◽

2021 ◽

Author(s):

J Stephen Nix ◽

Cristiane M Ida

Keyword(s):

Brain Tumors ◽

Molecular Diagnosis ◽

Genetic Alterations ◽

Genetic Alteration ◽

Molecular Testing ◽

Test Results ◽

Molecular Test ◽

Molecular Tests ◽

Clinically Significant ◽

Selection Of

Abstract Molecular testing has become part of the routine diagnostic workup of brain tumors after the implementation of integrated histomolecular diagnoses in the 2016 WHO classification update. It is important for every neuropathologist to be aware of practical preanalytical, analytical, and postanalytical factors that impact the performance and interpretation of molecular tests. Prior to testing, optimizing tumor purity and tumor amount increases the ability of the molecular test to detect the genetic alteration of interest. Recognizing basic molecular testing platform analytical characteristics allows selection of the optimal platform for each clinicopathological scenario. Finally, postanalytical considerations to properly interpret molecular test results include understanding the clinical significance of the detected genetic alteration, recognizing that detected clinically significant genetic alterations are occasionally germline constitutional rather than somatic tumor-specific, and being cognizant that recommended and commonly used genetic nomenclature may differ. Potential pitfalls in brain tumor molecular diagnosis are also discussed.

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A Comparison of Lung Ultrasound and Computed Tomography in the Diagnosis of Patients with COVID-19: A Systematic Review and Meta-Analysis

Diagnostics ◽

10.3390/diagnostics11081351 ◽

2021 ◽

Vol 11 (8) ◽

pp. 1351

Author(s):

Mengshu Wang ◽

Xufei Luo ◽

Ling Wang ◽

Janne Estill ◽

Meng Lv ◽

...

Keyword(s):

Computed Tomography ◽

Interstitial Pneumonia ◽

Lung Ultrasound ◽

Meta Analysis ◽

Diagnostic Odds Ratio ◽

Receiver Operating Curve ◽

Cochrane Library ◽

Molecular Tests ◽

Specificity And Sensitivity

Background Lung ultrasound (LUS) and computed tomography (CT) can both be used for diagnosis of interstitial pneumonia caused by coronavirus disease 2019 (COVID-19), but the agreement between LUS and CT is unknown. Purpose to compare the agreement of LUS and CT in the diagnosis of interstitial pneumonia caused by COVID-19. Materials and Methods We searched PubMed, Cochrane library, Embase, Chinese Biomedicine Literature, and WHO COVID-19 databases to identify studies that compared LUS with CT in the diagnosis of interstitial pneumonia caused by COVID-19. We calculated the pooled overall, positive and negative percent agreements, diagnostic odds ratio (DOR) and the area under the standard receiver operating curve (SROC) for LUS in the diagnosis of COVID-19 compared with CT. Results We identified 1896 records, of which nine studies involving 531 patients were finally included. The pooled overall, positive and negative percentage agreements of LUS for the diagnosis of interstitial pneumonia caused by COVID-19 compared with CT were 81% (95% confidence interval [CI] 43–99%), 96% (95% CI, 80–99%, I2 = 92.15%) and 80% (95%CI, 60–92%, I2 = 92.85%), respectively. DOR was 37.41 (95% CI, 9.43–148.49, I2 = 63.9%), and the area under the SROC curve was 0.94 (95% CI, 0.92–0.96). The quality of evidence for both specificity and sensitivity was low because of heterogeneity and risk of bias. Conclusion The level of diagnostic agreement between LUS and CT in the diagnosis of interstitial pneumonia caused by COVID-19 is high. LUS can be therefore considered as an equally accurate alternative for CT in situations where molecular tests are not available.

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Impact of the COVID-19 Vaccine on Asymptomatic Infection Among Patients Undergoing Pre-Procedural COVID-19 Molecular Screening

Clinical Infectious Diseases ◽

10.1093/cid/ciab229 ◽

2021 ◽

Cited By ~ 4

Author(s):

Aaron J Tande ◽

Benjamin D Pollock ◽

Nilay D Shah ◽

Gianrico Farrugia ◽

Abinash Virk ◽

...

Keyword(s):

United States ◽

Relative Risk ◽

Healthcare System ◽

The United States ◽

Asymptomatic Infection ◽

Screening Tests ◽

Molecular Screening ◽

Molecular Tests ◽

Asymptomatic Individuals ◽

The Impact

Abstract Background Several vaccines are now clinically available under emergency use authorization in the United States and have demonstrated efficacy against symptomatic COVID-19. The impact of vaccines on asymptomatic SARS-CoV-2 infection is largely unknown. Methods We conducted a retrospective cohort study of consecutive, asymptomatic adult patients (n = 39,156) within a large United States healthcare system who underwent 48,333 pre-procedural SARS-CoV-2 molecular screening tests between December 17, 2020 and February 8, 2021. The primary exposure of interest was vaccination with at least one dose of an mRNA COVID-19 vaccine. The primary outcome was relative risk of a positive SARS-CoV-2 molecular test among those asymptomatic persons who had received at least one dose of vaccine, as compared to persons who had not received vaccine during the same time period. Relative risk was adjusted for age, sex, race/ethnicity, patient residence relative to the hospital (local vs. non-local), healthcare system regions, and repeated screenings among patients using mixed effects log-binomial regression. Results Positive molecular tests in asymptomatic individuals were reported in 42 (1.4%) of 3,006 tests performed on vaccinated patients and 1,436 (3.2%) of 45,327 tests performed on unvaccinated patients (RR=0.44 95% CI: 0.33-0.60; p<.0001). Compared to unvaccinated patients, the risk of asymptomatic SARS-CoV-2 infection was lower among those >10 days after 1 st dose (RR=0.21; 95% CI: 0.12-0.37; p<.0001) and >0 days after 2 nd dose (RR=0.20; 95% CI: 0.09-0.44; p<.0001) in the adjusted analysis. Conclusions COVID-19 vaccination with an mRNA-based vaccine showed a significant association with a reduced risk of asymptomatic SARS-CoV-2 infection as measured during pre-procedural molecular screening. The results of this study demonstrate the impact of the vaccines on reduction in asymptomatic infections supplementing the randomized trial results on symptomatic patients.

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Evaluation of automated molecular tests for the detection of SARS‐CoV‐2 in pooled nasopharyngeal and saliva specimens

Journal of Clinical Laboratory Analysis ◽

10.1002/jcla.23876 ◽

2021 ◽

Author(s):

Hamad Al‐Hail ◽

Faheem Mirza ◽

Alaa Al Hashemi ◽

Muneera Naseer Ahmad ◽

Muhammad Iqbal ◽

...

Keyword(s):

Molecular Tests

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ID Learning Unit: Understanding and Interpreting Testing for Clostridium difficile

Open Forum Infectious Diseases ◽

10.1093/ofid/ofu007 ◽

2014 ◽

Vol 1 (1) ◽

Cited By ~ 6

Author(s):

Daniel A. Solomon ◽

Danny A. Milner

Keyword(s):

Clinical Practice ◽

Clostridium Difficile ◽

Basic Principles ◽

Multiple Tests ◽

Molecular Tests ◽

Different Types

Abstract Understanding and interpreting the molecular tests for Clostridium difficile is challenging because there are several different types of assays and most laboratories combine multiple tests in order to assess for presence of disease. This learning unit demonstrates the basic principles of each test along with its strengths and weaknesses, and illustrates how the tests are used in clinical practice.

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