Initial Screening Test Research Articles

Equilibrium-based COVID-19 diagnosis from routine blood tests: A sparse deep convolutional model

SARS-CoV2 (COVID-19) is the virus that causes the pandemic that has severely impacted human society with a massive death toll worldwide. Hence, there is a persistent need for fast and reliable automatic tools to help health teams in making clinical decisions. Predictive models could potentially ease the strain on healthcare systems by early and reliable screening of COVID-19 patients which helps to combat the spread of the disease. Recent studies have reported some key advantages of employing routine blood tests for initial screening of COVID-19 patients. Thus, in this paper, we propose a novel COVID-19 prediction model based on routine blood tests. In this model, we depend on exploiting the real dependency among the employed feature pool by a sparsification procedure. In this sparse domain, a hybrid feature selection mechanism is proposed. This mechanism fuses the selected features from two perspectives, the first is Pearson correlation and the second is a new Minkowski-based equilibrium optimizer (MEO). Then, the selected features are fed into a new 1D Convolutional Neural Network (1DCNN) for a final diagnosis decision. The proposed prediction model is tested with a new public dataset from San Raphael Hospital, Milan, Italy, i.e., OSR dataset which has two sub-datasets. According to the experimental results, the proposed model outperforms the state-of-the-art techniques with an average testing accuracy of 98.5% while we employ only less than half the size of the feature pool, i.e., we need only less than half the given blood tests in the employed dataset to get a final diagnosis decision.

Utility of Cell Block with p53 Immunostain in Diagnosing Urothelial Carcinoma

Background: Urine cytology is an initial noninvasive screening test done in patients with suspected urothelial carcinoma. The objective of this study was to compare the sensitivity of conventional smear cytology with cell block technique for the diagnosis of malignant cells in urine and to assess the efficacy of p53 immuno-marker in the diagnosis and prognosis of urinary bladder cancer.
 Methodology: The study was carried out in the department of Histopathology, Pakistan Institute of Medical Sciences(PIMS), Islamabad. Cell blocks and cytology smears and were prepared from urine samples of 80 patients of urothelial carcinoma and p53 stain was applied. Data was analyzed using version 21. Sensitivity of conventional smear and cell block techniques were calculated for both low and high grade urothelial carcinomas.
 Results:The sensitivity of detecting atypical cells using conventional smear was 31% and 70.6% for low grade and high grade urothelial tumors respectively. The sensitivity increased to 41.4% and 84.3% for low and high grade urothelial carcinomas respectively with cell block technique. Positive p53 stain was seen in 13.8% of cases with low grade tumors and 66.7% cases with high grade tumors. Chi-square test was used to find the association of cytology findings with the histologic grade.
 Conclusion: Sensitivity of urine cell blocks is higher than the conventional smear method for detecting high grade lesions. It can be used as an efficient non-invasive technique and an adjunct tool for the determination of disease relapse and overall survival in patients.
 Keywords: Carcinoma, Cytology, P53 Protein, Urine

Predictive accuracy of the ABCD progression display among patients with keratoconus: A historic cohort analysis.

To evaluate the accuracy of the ABCD Progression Display and the ABCD grading system in a population of adult patients with keratoconus. A retrospective cohort analysis of all adult patients with keratoconus followed at the Shamir Medical Center between 2012 and 2017. A recommendation by the cornea specialist to undergo corneal crosslinking (CXL) was used as a surrogate of ectasia progression. The ABCD grading was not available to the treating physician and was computed post-hoc. Sensitivity and specificity of the ABCD Progression Display was calculated, and multivariate regression was used to estimate the risk to undergo CXL when the ABCD Progression Display indicated progression. The ABCD grading was compared between patients who required CXL to those who did not. A single eye of each patient was included. Sensitivity and specificity of the ABCD Progression Display were 82% and 73%, respectively. A multivariable model adjusted for possible confounders, found that ABCD Progression was associated with a 7-fold risk of undergoing CXL compared to a patient in whom progression was not recorded in the ABCD Progression Display (OR = 7.55; 95% CI = 3.82-14.93, p < 0.001). 293 eyes of 293 patients were analysed. Mean age at presentation was 26.92 ± 6.12 years. In 68 eyes, progression of keratoconus was recorded and CXL was performed (CXL-group). The ABCD Progression Display demonstrated adequate sensitivity and specificity and high predictive capabilities of keratoconus progression. It can be effectively utilized as an initial screening test in adults with keratoconus.

Increasing test specificity without impairing sensitivity: lessons learned from SARS-CoV-2 serology

BackgroundSerological tests are widely used in various medical disciplines for diagnostic and monitoring purposes. Unfortunately, the sensitivity and specificity of test systems are often poor, leaving room for false-positive and...

Performance of Idylla KRAS assay on extracted DNA and de-stained cytology smears: Can we rescue small sample?

ObjectiveKRAS is a frequently mutated gene in cancers, and with recent FDA-approved targeted therapy for the G12C mutation, testing for KRAS variants is essential. We evaluated the performance of the Idylla KRAS assay on extracted DNA and cytology smears in order to expand the utility of the assay. MethodsIn total, fifty-seven human samples were analyzed. Idylla results from sixteen DNA extracted from formalin-fixed, paraffin-embedded tissues (FFPE DNA) and thirty cytology smears were compared to the reference method. We evaluated the performance of the Idylla assay using corresponding cytology smears to rescue cellblocks or surgical blocks that were quantity not sufficient (QNS) for next generation sequencing (NGS). ResultIn the FFPE DNA cohort, 10 ng DNA input yielded valid results in all 16 samples, with 15 of 16 (93 %) concordant with NGS findings. In the cytology smear cohort, the Idylla KRAS assay demonstrated 100 % concordance with previous NGS results in 30 cases. In the QNS cohort, the assay was valid in all cases and KRAS mutations were identified in 3 of 11 cytology smears, including one G12C mutation. ConclusionThe Idylla KRAS assay is a high-performing, feasible, and convenient option for testing extracted DNA and cytology smears. It rescues QNS samples allowing it to be integrated into the molecular workflow as an initial screening test with remarkably quick turnaround times.

Henipavirus sero-surveillance in horses and pigs from Northern Nigeria

Hendra virus and Nipah virus are considered to be emerging viruses and cause severe zoonotic diseases, which occur in humans who have had close contact with horses and pigs in Australia and Asia, respectively. Both viruses belong to the genus Henipavirus. Although there are large populations of horses and pigs in northern Nigeria, no previous studies in this region have investigated henipavirus sero-surveillance in horses and pigs using the gold standard test, the serum neutralization test (SNT). A total of 536 apparently healthy horses and 508 apparently healthy pigs were sampled in northern Nigeria in 2018. Serum samples were tested for Hendra virus and Nipah virus-specific antibodies using either the Henipavirus Luminex binding assays for horses or the Hendra virus Competitive ELISA and Nipah virus Indirect ELISA for pigs as initial screening tests, followed by the confirmatory Hendra and Nipah virus SNT for both species, according to accredited protocols at the Australian Centre for Disease Preparedness. Although some horse and pig samples crossed-reacted or reacted weakly in the screening test, confirmatory SNT for all of them proved negative. This study reveals the absence of Hendra and Nipah antibodies in horses and pigs in northern Nigeria, which is consistent with the absence of observable disease in the field. However, the continuous inter and intra-trans-boundary animal movement and trade in Nigeria calls for the continuous evaluation of the henipavirus status of susceptible animals to safeguard both animal and human health.

A comparative study of sonographic evaluation of thyroid nodules, using TIRADS, with fine needle aspiration cytology

Various imaging modalities have been used in the diagnosis of thyroid diseases. Ultrasonography followed by USG guided FNAC is usually done in evaluating any thyroid nodule that is palpable on physical examination. FNAC often used as the initial screening test for diagnosis of thyroid nodule. This study was a cross-sectional study where patients with palpable thyroid nodules or clinically evident thyroid disease (hypothyroidism/hyperthyroidism) were evaluated by ultrasound examination, which were correlated with FNAC of the patient. Statistical software SPSS (version 20.0) and Microsoft Excel were used to carry out the statistical analysis of data. It was concluded that conclusion high resolution ultrasound is an accurate technique to assess the morphology of thyroid nodules.

Laboratory Diagnosis of Drug of Abuse-Latest Update

Substance abuse, also known as drug abuse, is the use of a drug in amounts or by methods which are harmful to the individual or others. It is a form of substance-related disorder. Substance use disorders (SUD) are mental health conditions that arise from chronic drug use. There is an increased recognition of this problem in Saudi Arabia. Drugs of abuse testing is the detection of one or more illegal and/or prescribed substances in the urine, blood, saliva, hair, or sweat. Testing detects substances not normally found in the body. Drug abuse testing usually involves an initial screening test followed by a second test that identifies and/or confirms the presence of a drug or drugs. Initial screening is done by urine tests and confirmation is done by blood tests. Major drug class screened are Amphetamines, Barbiturates, Benzodiazapines, Cannibinoids, Cocaine, methadone and opiates. In this article we reviewed lab diagnosis of drug of abuse.

Role of immunocytochemistry in cervical cancer screening.

The cervical cancer screening has been based conventionally on cytologic analysis. With advances in understanding the role of human papillomavirus, cotesting has been applied. But most of the patients subjected to colposcopy did not benefit, except in cases with HSIL [high-grade squamous intraepithelial lesion] cytology. Because of this, a step to increase the sensitivity to detect cancers and pre-cancers but with higher specificity with minimal overdiagnosis leading to prevention of unindicated cervical biopsies is highly desired. Such triaging step in cases with abnormal screening results is expected to minimize invasive interventions because of low false positivity. With availability of methodologies leading to quantitatively and qualitatively enhanced cell-blocks from residual liquid based cytology specimens, immunostaining can be performed for multiple immunomarkers with potential objectivity to triage initial screening test results. This is enhanced further with inclusion of AV marker in the cell-blocks and application of SCIP (subtractive coordinate immunoreactivity pattern) approach. The cell-blocks are also resource for performing other ancillary studies including molecular pathology and proteomics/metabolomics as potential tests in future. This review explores application of residual liquid based cytology specimen for cell-blocking with application of ancillary studies in algorithmic manner as adjunct to ASCCP management guidelines for improved patient care.

Late-night salivary cortisol and cortisone should be the initial screening test for Cushing's syndrome.

Endogenous Cushing’s syndrome (CS) poses considerable diagnostic challenges. Although late-night salivary cortisol (LNSC) is recommended as a first-line screening investigation, it remains the least widely used test in many countries. The combined measurement of LNSC and late-night salivary cortisone (LNS cortisone) has shown to further improve diagnostic accuracy. We present a retrospective study in a tertiary referral centre comparing LNSC, LNS cortisone, overnight dexamethasone suppression test, low-dose dexamethasone suppression test and 24-h urinary free cortisol results of patients investigated for CS. Patients were categorised into those who had CS (21 patients) and those who did not (33 patients). LNSC had a sensitivity of 95% and a specificity of 91%. LNS cortisone had a specificity of 100% and a sensitivity of 86%. With an optimal cut-off for LNS cortisone of >14.5 nmol/L the sensitivity was 95.2%, and the specificity was 100% with an area under the curve of 0.997, for diagnosing CS. Saliva collection is non-invasive and can be carried out at home. We therefore advocate simultaneous measurement of LNSC and LNS cortisone as the first-line screening test to evaluate patients with suspected CS.

Early universal screening of gestational diabetes in a university hospital in Thailand

A total of 1016 pregnant women attending antenatal clinic before 20 weeks of gestation during September 2018 to February 2019 were included in a cohort study with repeated cross-sectional assessments. The study was aimed to determine prevalence and characteristics of gestational diabetes mellitus (GDM) and pregnancy outcomes by early universal screening approach. GDM screening was performed during first visit and repeated during 24–28 weeks of gestation, as necessary, using a 50-g glucose challenge test followed by a 100-g oral glucose tolerance test for GDM diagnosis. Overall prevalence of GDM was 18.6%. A significantly higher prevalence of GDM was observed among high-risk than low-risk women (21.3% vs. 13.1%, p = 0.002). GDM among low-risk women contributed to 23.3% of all GDM cases. The majority of GDM (76.2%) were diagnosed before 20 weeks of gestation, with 74.5% occurring in high-risk women and 81.8% occurring in low-risk women. When initial screening tests were normal, risk of GDM diagnosed during 24–28 weeks was 6.0% (7.5% among high-risk women and 3.1% among low-risk women). Compared to those without GDM, women with GDM significantly had lower gestational weight gain (p < 0.001), higher prevalence of preeclampsia (p = 0.001), large for gestational age (LGA) (p = 0.034) and macrosomia (p = 0.004). These outcomes were more pronounced among high-risk women with GDM. Impact Statement What is already known on this subject? Universal GDM screening is recommended during 24–28 weeks of gestation, either by 1- or 2-step approach. Some also recommend early GDM screening among high-risk women. Prevalence of early-onset GDM varies between studies and benefits of early diagnosis and treatment are still controversial. What do the results of this study add? Early universal GDM screening identified more women with GDM and majority could be diagnosed before 20 weeks of gestation. GDM among low-risk women contributed to 23.3% of all cases. Adverse pregnancy outcomes were more common among high-risk women with GDM. This approach could be useful and can be implemented in other settings, especially those that serve high-risk population or with high GDM prevalence. What are the implications of these findings for clinical practice and/or further research? Early universal GDM screening should be considered in settings with high prevalence of GDM and high-risk women. However, benefits of early detection and treatment of GDM should be determined in more details in the future, especially in terms of cost-effectiveness and improvement in pregnancy outcomes.

Bayesian estimation of sensitivity and specificity of a rapid mastitis test kit, bacterial culture, and PCR for detection of Staphylococcus aureus, Streptococcus species, and coliforms in bovine milk samples

Our objectives were to evaluate the diagnostic accuracy of a rapid and novel immunochromatography-based mastitis kit that includes 3 independent tests to detect coliforms (Escherichia coli or Klebsiella pneumoniae), Streptococcus spp., and Staphylococcus aureus. The kit was developed to facilitate diagnostic-based mastitis treatment. Validation of the kit was based on 154 aseptically collected mastitis samples from 2 clinical herds (clinical population) and 120 milk samples from 3 nonclinical herds (nonclinical population) without clinical cases at the time of enrollment. One herd sampled at different times was common to both populations. A 3-test in 2-population Bayesian latent class model with uniform priors for all test parameters except specificity of culture, which was modeled informatively, was used to estimate sensitivity (Se) and specificity (Sp) of the test kit, culture, and PCR at the cow level. The mastitis test kit's 96.9% Sp for Streptococcus spp. had a low false positive percentage (3.1%), which, together with the kit's rapid turnaround time for results, makes it a suitable initial screening test that producers can use to identify clinical cows to treat based on Streptococcus spp. mastitis in kit-positive results. Due to the 60.4% kit Se, producers should follow up on Streptococcus spp. kit-negative cows using a confirmatory test such as PCR (Sp of 98.4%) or culture (Sp of 99.6%). In contrast, aerobic culture had Se of 76.5% and Sp of 99.6% for Streptococcus spp. Similarly, the Sp of the kit (98.2%) and culture (99.8%) for Staph. aureus were particularly high, and even though the kit's Se (61.0%) was lower than culture (88.4%; posterior probability of difference 98%), the kit could be beneficial before use of a confirmatory test for kit-negative samples due to its ease and rapid turnaround time. Mostly, quantitative real-time (q)PCR outperformed the kit's Se (37.7%) and Sp (92.9%) for coliforms, as well as the kit's Se (60.4%) for Streptococcus spp. However, qPCR may require more technical skills and turnaround time for final results. Use of the on-farm mastitis test kit evaluated in the present study could enhance sustainable antimicrobial drug use by rapidly identifying Streptococcus mastitis for targeted treatment. Furthermore, the kit may be used in a Staph. aureus outbreak where cows can be rapidly screened to identify cases for segregation or culling during an outbreak and kit-negative cows further confirmed by milk culture or qPCR. However, the cost-effectiveness of such an approach has not been investigated.

Kashmiri refugees at the verge of hepatitis B and C epidemic in the State of Azad Jammu and Kashmir, Pakistan.

ABSTRACTOBJECTIVE To determine the seroprevalence of hepatitis B and C among immigrants residing refugee camps in Muzaffarabad, Azad Kashmir, Pakistan, and to identify possible risk factors for hepatitis B virus (HBV) and hepatitis C virus (HCV) transmission.METHODS Around 1,225 individuals inhabiting Muzaffarabad refugee camps, participated in the study. A qualitative Immuno-Chromatographic Technique was used for initial screening and PCR test was used for detection of HBV and HCV in participants. The major risk factors for HBV and HCV transmission were assessed using a questionnaire approach.RESULTS Around 86 (7.0%) individuals were observed for hepatitis B surface antigen (HBsAg) presence, and 215 (17.5%) individuals were found positive for Anti-HCV. Only 32 (2.6%) individuals were confirmed for HBV DNA and 126 (10.3%) individuals were positive for HCV RNA after PCR. Demographically, both HBsAg and Anti-HCV were found more prevalent in female (4.4% HBsAg and 10.8% Anti-HCV) population as compared to male (2.6% HBsAg and 6.7% Anti-HCV) population. Surprisingly, the HBsAg (23.5%) and Anti-HCV (41.1%) appeared to be more frequent in the age group 62–75 years. Previous history of hepatitis in the family (p < 0.0001), blood transfusion (p = 0.0197) dental treatment (p < 0.0001) and tattooing or piercing on any part of the body (p = 0.0028) were assessed as significant risk factors in HBV and HCV transmission.CONCLUSIONS Presence of 7.0% HBsAg and 17.5% Anti-HCV in a small fragment of the migrant population cannot be overlooked. Lack of awareness among people and negligence of health department could escalate the situation.

Out-of-Pocket Costs for Colposcopy Among Commercially Insured Women From 2006 to 2019

(Abstracted from Obstet Gynecol 2022;139:113–115) Colposcopy is an evidence-based, recommended procedure for women with an abnormal initial cervical cancer screening test result. Cervical cancer screening modalities, including Papanicolaou testing and human papillomavirus testing, are covered by the Affordable Care Act without consumer cost sharing for average-risk, age-eligible women.

Establishment of Cutoff Values for Newborn Screening of Six Lysosomal Storage Disorders by Tandem Mass Spectrometry.

ObjectiveLysosomal storage disorders (LSDs) are becoming increasingly important in newborn screening, and tandem mass spectrometry (MS/MS) is widely used in newborn screening for LSDs through measurement of enzymatic activities in dried blood spots (DBSs). Overall, the determination of the cutoff value is important in such screening, and different laboratories have different methods of determining this value; most do not use a fixed cutoff value but rather calculate the corresponding batch cutoff value based on each batch of experimental data. In this study, we used MS/MS to screen for LSDs and sought to find an appropriate method to establish the cutoff value for LSD screening.MethodsA total of 38,945 samples from newborn blood tablets collected from various maternity hospitals in six cities in Shandong province, including Jinan, Dezhou, Heze, Linyi, Weifang, and Zibo, were tested using a Waters Xevo TQD tandem mass spectrometer; the experimental data were analyzed with MassLynx V4.1. The laboratory used 30% of the median GLA enzyme activity and 20% of the median ABG, ASM, GALC, IDUA, and GAA enzyme activities in every test as the cutoff values for that batch of experiments.ResultsThere were 254 suspicious positives in the initial screening test, including one case of Gaucher disease, one of Niemann-Pick disease, 47 of Krabbe disease, four of MPS-I, 21 of Fabry disease, and 180 of Pompe disease. After genetic screening, 11 children were diagnosed, including three with Pompe disease, three with Fabry disease, and five with Krabbe disease. In addition, the enzyme activity cutoff value of this experiment showed seasonal variation, which was initially believed to be related to the ambient temperature, such as the effect of ambient temperature on the human body or the temperature when the blood tablets dried naturally.ConclusionOverall, MS/MS can be used in LSD screening, and using different cutoff values in each batch of experiments is feasible. The ambient temperature might be a reason why the enzyme activity cutoff value has seasonal variation. More samples are needed to develop a method of determining cutoff values in laboratories.

A global view of adherence to colonoscopy follow-up in cascade screening of colorectal cancer.

To overview the colonoscopy adherence in cascade screening of colorectal cancer (CRC) and evaluate potential influence of the initial tests based on an ecological evaluation. The performance of the initial screening tests and adherence to subsequent colonoscopy were extracted from relevant studies published up to 16 October 2020. The age-standardised incidence (ASRi) of CRC in populations in the year of screening was derived from the Cancer Statistics. One hundred sixty-six observational studies and 60 experimental studies were identified. Most studies applied cascade screening with faecal occult blood tests (FOBTs) as an initial test. The adherence to colonoscopy varied greatly across populations by continents, gross national income and type of initial tests, with a median (interquartile range) of 79.8% (63.1%-87.8%) in observational studies and 82.1% (66.7%-90.4%) in randomised trials. The adherence was positively correlated with the ASRi of CRC (r = 0.145, p =0.023) and positive predictive value (PPV) of the initial tests (r = 0.206, p = 0.002) in observational studies and correlated with ASRi of CRC (r = 0.309, p =0.002) and sensitivity of the initial tests (r = -0.704, p = 0.003) in experimental studies. Adherence to colonoscopy varies greatly across populations and is related with performance of the initial tests, indicating the importance to select appropriate initial tests.

Correlation of Treponemal Chemiluminescent Microparticle Immunoassay Screening Test Signal Strength Values With Reactivity of Confirmatory Testing.

Automated chemiluminescent microparticle immunoassays (CMIAs) are the most common first step at high-volume laboratories for syphilis screening. If the initial screening test is reactive, 1 more treponemal test is required, resulting in increased cost. In this multicenter study, we aimed to determine the correlation between the CMIA signal-to-cutoff ratio (S/Co) and the confirmatory tests to reduce unnecessary confirmatory testing. Eight hospitals from 5 provinces participated in this study. All laboratories used Architect Syphilis TP CMIA (Abbott Diagnostics, Abbott Park, IL) for initial screening. Treponema pallidum hemagglutination (TPHA), rapid plasma reagin (RPR), and fluorescent treponemal antibody absorption (FTA-ABS) were used as confirmatory tests according to the reverse or European Centre for Disease Prevention and Control algorithms. A receiver operating characteristic analysis was used to determine the optimal S/Co ratio to predict the confirmation results. We evaluated 129,346 serum samples screened by CMIA between January 2018 and December 2020. A total of 2468 samples were reactive; 2247 (91%) of them were confirmed to be positive and 221 (9%) were negative. Of the 2468 reactive specimens, 1747 (70.8%) had an S/Co ratio ≥10.4. When the S/Co ratios were ≥7.2 and ≥10.4, the specificity values were determined to be 95% and 100%, respectively. In a subgroup of 75 CMIA-positive patients, FTA-ABS was performed and 62 were positive. Among these FTA-ABS-positive patients, 24 had an S/Co ratio <10.4, and negative TPHA and RPR. We propose a potentially cost-effective reverse screening algorithm with a treponemal CMIA S/Co ratio ≥10.4, obviating the need for secondary treponemal testing in about 71% of the screening-reactive samples. This would substantially reduce the confirmatory testing volume and laboratory expenses. However, in high-risk group patients with CMIA positive results, S/Co ratio <10.4, and negative TPHA and RPR, FTA-ABS may be used for confirmation.

Review of MIS-C Clinical Protocols and Diagnostic Pathways: Towards a Consensus Algorithm.

BackgroundThe emergence of multisystem inflammatory syndrome in children (MIS-C) during the severe acute respiratory syndrome coronavirus 2 pandemic led to the development of institutional clinical pathways based on expert opinion. We assessed North American paediatric centres’ adaptation to MIS-C and analysed the degree of agreement between algorithms on tiered clinical investigations.MethodsThis study evaluated MIS-C diagnostic algorithms from 50 tertiary centres developed between May 2020 and December 2021 in the United States and Canada obtained online and through colleagues in various institutions. Descriptive statistics were used to analyse results.ResultsAll clinical pathways used a tiered approach, and most required coronavirus disease 2019 polymerase chain reaction testing on presentation. Over one-quarter used a 24-hour fever to initiate investigations, and another quarter used 3 days. Basic biochemical workup was performed in all centres on presentation (complete blood count, inflammatory markers, hepatic, and renal functions). Specialized investigation was generally reserved for secondary testing (cardiac biomarkers, electrocardiogram and echo, and coagulation panel). Institutions were divided on several investigations for tier distribution, including urine studies, blood cultures, chest radiograph, and severe acute respiratory syndrome coronavirus 2 serology. Subspecialty consultations were reserved for second-line testing, including cardiology, infectious disease, and rheumatology. Finally, we propose a composite algorithm representative of the consulted pathways.ConclusionsFaced with an unprecedented clinical challenge, paediatric institutions responded swiftly with evaluation standardization, adapting to evolving knowledge. Most pathways agreed on initial basic screening tests followed by secondary workup including cardiac investigations. These protocols, developed during a high level of uncertainty, require comparative assessment on efficacy and superiority.

BRAF mutation testing for patients diagnosed with stage III or stage IV melanoma: practical guidance for the Australian setting.

Targeted therapy (BRAF inhibitor plus MEK inhibitor) is now among the possible treatment options for patients with BRAF mutation-positive stage III or stage IV melanoma. This makes prompt BRAF mutation testing an important step in the management of patients diagnosed with stage III or IV melanoma; one that can help better ensure that the optimal choice of systemic treatment is initiated with minimal delay. This article offers guidance about when and how BRAF mutation testing should be conducted when patients are diagnosed with melanoma in Australia. Notably, it recommends that pathologists reflexively order BRAF mutation testing whenever a patient is found to have American Joint Committee on Cancer (AJCC)/Union for International Cancer Control (UICC) stage III or IV melanoma (i.e., any metastatic spread beyond the primary tumour) and that patient's BRAF mutation status is hitherto unknown, even if BRAF mutation testing has not been specifically requested by the treating clinician (in Australia, Medicare-subsidised BRAFV600 mutation testing does not need to be requested by the treating clinician). When performed in centres with appropriate expertise and experience, immunohistochemistry (IHC) using the anti-BRAF V600E monoclonal antibody (VE1) can be a highly sensitive and specific means of detecting BRAFV600E mutations, and may be used as a rapid and relatively inexpensive initial screening test. However, VE1 immunostaining can be technically challenging and difficult to interpret, particularly in heavily pigmented tumours; melanomas with weak, moderate or focal BRAFV600E immunostaining should be regarded as equivocal. It must also be remembered that other activating BRAFV600 mutations (including BRAFV600K), which account for ∼10-20% of BRAFV600 mutations, are not detected with currently available IHC antibodies. For these reasons, if available and practicable, we recommend that DNA-based BRAF mutation testing always be performed, regardless of whether IHC-based testing is also conducted. Advice about tissue/specimen selection for BRAF mutation testing of patients diagnosed with stage III or IV melanoma is also offered in this article; and potential pitfalls when interpreting BRAF mutation tests are highlighted.

Abdominal Fat Pad Fine-Needle Aspiration for Diagnosis of Cardiac Amyloidosis in Patients with Non-Ischemic Cardiomyopathy.

The diagnosis of cardiac amyloidosis is frequently delayed because histological confirmation is often challenging. Few studies have attempted to clarify the utility and safety of abdominal fat pad fine-needle aspiration (FPFNA) for an initial screening test in patients with suspected cardiac amyloidosis.This study included 77 consecutive patients with suspected non-ischemic cardiomyopathy who had left ventricular dysfunction and/or hypertrophy. All patients underwent abdominal FPFNA and an endomyocardial biopsy. In all patients, the abdominal FPFNA could be performed within less than 5 minutes with no complications; however, in 1 patient (1.3%), the obtained specimen was too small to evaluate. Among the remaining 76 patients, 5 (6.6%) were positive for amyloid (FPFNA[+]) and 7 (9.2%), including the 5 FPFNA[+], were diagnosed with cardiac amyloidosis (AL = 1, ATTR = 6) by endomyocardial biopsy. Positive abdominal FPFNAs indicated cardiac amyloidosis with high accuracy (sensitivity, 71.4%; specificity, 100%).Positive abdominal FPFNAs are directly linked to diagnoses of cardiac amyloidosis. Abdominal FPFNA is simple and useful for the initial screening test for cardiac amyloidosis in patients with non-ischemic cardiomyopathy.