The diagnosis of growth hormone deficiency remains a judgment call – and that is good

The diagnosis of GHD still does not reflect evidence-based and generally accepted practice, and reliance on growth hormone stimulation testing (GST) leads to a high rate of false positive diagnosis of idiopathic isolated GHD (IIGHD). While searching for more definitive indicators of GHD is attractive, it should not distract from currently available steps to reduce erroneous IIGHD diagnoses. This paper describes opportunities to improve the accuracy of the GST which include: 1) meticulous selection of candidates for GST, since a low prevalence of GHD among short children in general is a major factor undermining the test’s diagnostic accuracy; 2) departure from traditional pass/fail diagnostic GH cutoffs towards, instead, formulation of diagnoses along a continuum that spans actual GHD -> provisional GHD -> not GHD; 3) response to the provisional diagnosis of IIGHD based on GST with additional post-test observation or alternative growth-promoting interventions rather than immediate hGH treatment; 4) re-examination and often correction of a prior IIGHD diagnosis with the onset of puberty. Modern medicine is increasingly offering diagnostic tests that aim to eliminate the need for provisional diagnoses. But a pitfall of such a “definitive” test for GHD would be the temptation to respond to its results definitively. Given the nuances, variations, and fluctuations in GH axis function over time, children evaluated for growth concerns are still best served by clinical judgment that combines thoroughness, patience, flexibility, and healthy skepticism into the diagnosis of GHD.

Identifying Inconclusive Data in the SARS-CoV-2 Molecular Diagnostic Using Nucleocapsid Phosphoprotein Gene as Target

ABSTRACT Context: The gold standard test to identify the presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in coronavirus disease 2019 (COVID-19) patients is the real-time reverse transcription quantitative polymerase chain reaction (RT-qPCR), but the inconclusive data and presence of false positive diagnosis remain the major problem of this approach. Objective: To compare the fitness of two primers sets to the SARS-CoV-2 nucleocapsid phosphoprotein (NP) gene in the molecular diagnosis of COVID-19, we verify the inconclusive data and confidence of high cycle threshold (Ct) values in the SARS-CoV-2 detection. Design: The 970 patient samples were tested using United States Centers for Disease Control and Prevention protocol. We compared the fitness of two primers sets to two different regions of NP gene. In addition, we check the consistency of positive samples with high Ct values by retesting extracted SARS-CoV-2 RNA or by second testing of patients. Results: The N1 and N2 displayed similar fitness during testing with no differences between Ct values. Then, we verified security range Cts related to positive diagnostic with Ct above 34 failing in 21/32 (65.6%) after retesting of samples. The samples patients with Ct above 34.89 that were doubly positive revealed a low sensitivity (52.4%) and specificity (63.6%) of the test in samples with Ct above 34. Conclusions: It is secure to use one primer set to the NP gene to identify SARS-CoV-2 in samples. However, samples with high Ct values may be considered inconclusive and retested to avoid false positive diagnosis.

Mimics of perineural tumor spread in the head and neck

Perineural spread (PNS) is an important potential complication of head and neck malignancy, as it is associated with decreased survival and a higher risk of local recurrence and metastasis. There are many review articles focused on the imaging findings of PNS. However, a false-positive diagnosis of PNS can be just as harmful to the patient as an overlooked case. In this manuscript, we delineate and classify various imaging mimics of PNS. Mimics can be divided into the following categories: normal variants (including vascular structures and failed fat suppression), infections, inflammatory disease (including granulomatous disease and demyelination), neoplasms, and post-traumatic/surgical changes. Knowledge of potential mimics of PNS will prevent false-positive imaging interpretation, and enable appropriate oncologic management.

A case of false-positive diagnosis of skin melanoma in a child

Diagnosis of skin melanoma (SM) in children is a complex clinical and morphoimmunological problem. The rare occurrence, difficult interpretation of histological and immunohistochemical picture explain the error rate in the diagnosis of SM reaching 28.8 %. This article presents a clinical case of false-positive diagnosis of SM. As a result of a detailed assessment of the anamnesis, examination, revision of histological preparations and conducting an immunohistochemical study in the reference center, the diagnosis of SM was excluded.

The Use of Standardized DSM-5 Symptoms Increases the Likelihood of a False-Positive Diagnosis of Bipolar Disorder in Children Aged 6-12 in the United States

Over the past ten years, there has been a 10% increase in the misdiagnosis of psychiatric disorders in the United States. This is significantly important as the rate of misdiagnosis of pediatric bipolar disorder is on the rise. I studied causes of misdiagnosing bipolar disorder, specifically in children, and what causes psychiatrists to continue to misdiagnose children despite knowing that children are still growing and have radical symptoms, in order to develop a strategy that decreases the number of misdiagnoses of pediatric bipolar disorder. Several studies have shown that one of the leading causes of misdiagnosis is the broad symptoms listed in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5). The revisions to the DSM-4 involved the addition of about 14 disorders. The symptoms listed in the DSM-5 are targeted towards adults. However, the DSM-5 is being used to diagnose children. I analyzed longitudinal studies done on school-aged children to assess how many children are misdiagnosed. The study showed that about 2.5% of the children were diagnosed with bipolar disorder based on the symptoms of the DSM-5. However, at the end of the study, the children did not have symptoms of bipolar disorder anymore. The results supported the claim that children are being over-diagnosed with bipolar disorder. I hypothesize that children should not be diagnosed with severe disorders until they are older and developed, unless they have severe symptoms. Based on the results of this study, pediatric bipolar disorder should be diagnosed based on alternative diagnostic methods such as using collateral history and offering therapy rather than prescribing children with medication. It is crucial that the misdiagnosis rate goes down because children should not be dependent on medications when they are still growing and developing.

Diagnostic Accuracy in Teleneurological Stroke Consultations

Background: The accuracy of diagnosing acute cerebrovascular disease via a teleneurology service and the characteristics of misdiagnosed patients are insufficiently known. Methods: A random sample (n = 1500) of all teleneurological consultations conducted between July 2015 and December 2017 was screened. Teleneurological diagnosis and hospital discharge diagnosis were compared. Diagnoses were then grouped into two main categories: cerebrovascular disease (CVD) and noncerebrovascular disease. Test characteristics were calculated. Results: Out of 1078 consultations, 52% (n = 561) had a final diagnosis of CVD. Patients with CVD could be accurately identified via teleneurological consultation (sensitivity 95.2%, 95% CI 93.2–96.8), but we observed a tendency towards false-positive diagnosis (specificity 77.4%, 95% CI 73.6–80.8). Characteristics of patients with a false-negative CVD diagnosis were similar to those of patients with a true-positive diagnosis, but patients with a false-negative CVD diagnosis had ischemic heart disease less frequently. In retrospect, one patient would have been considered a candidate for intravenous thrombolysis (0.2%). Conclusions: Teleneurological consultations are accurate for identifying patients with CVD, and there is a very low rate of missed candidates for thrombolysis. Apart from a lower prevalence of ischemic heart disease, characteristics of “stroke chameleons” were similar to those of correctly identified CVD patients.

Hydrogen–methane breath testing results influenced by oral hygiene

The measurement of hydrogen–methane breath gases is widely used in gastroenterology to evaluate malabsorption syndromes and bacterial overgrowth. Laboratories offering breath testing provide variable guidance regarding oral hygiene practices prior to testing. Given that oral dysbiosis has the potential to cause changes in breath gases, it raises concerns that oral hygiene is not a standard inclusion in current breath testing guidelines. The aim of this study was to determine how a pre-test mouthwash may impact hydrogen–methane breath test results. Participants presenting for breath testing who had elevated baseline gases were given a chlorhexidine mouthwash. If a substantial reduction in expired hydrogen or methane occurred after the mouthwash, breath samples were collected before and after a mouthwash at all breath sample collection points for the duration of testing. Data were evaluated to determine how the mouthwash might influence test results and diagnostic status. In 388 consecutive hydrogen–methane breath tests, modifiable elevations occurred in 24.7%. Administration of a chlorhexidine mouthwash resulted in significantly (p ≤ 0.05) reduced breath hydrogen in 67% and/or methane gas in 93% of those consenting to inclusion. In some cases, this modified the diagnosis. Mean total gas concentrations pre- and post-mouthwash were 221.0 ppm and 152.1 ppm (p < 0.0001) for hydrogen, and 368.9 ppm and 249.8 ppm (p < 0.0001) for methane. Data suggest that a single mouthwash at baseline has a high probability of returning a false positive diagnosis. Variations in gas production due to oral hygiene practices has significant impacts on test interpretation and the subsequent diagnosis. The role of oral dysbiosis in causing gastrointestinal symptoms also demands exploration as it may be an underlying factor in the presenting condition that was the basis for the referral.

Combined RT-qPCR and Pyrosequencing of a SARS-CoV-2 Spike Glycoprotein Polybasic Cleavage Motif Uncovers Rare Pediatric COVID-19 Spectrum Diseases of Unusual Presentation

BackgroundSurveillance of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections is essential for the global containment measures with regard to the ongoing pandemic. Diagnostic gold standard is currently reverse transcription of the (+)RNA genome and subgenomic RNAs and subsequent quantitative polymerase chain reaction (RT-qPCR) from nasopharyngeal swabs or bronchoalveolar lavages. In order to further improve the diagnostic accuracy, particularly for the reliable discrimination between negative and false-negative specimens, we propose the combination of the RT-qPCR workflow with subsequent pyrosequencing of a S-gene amplicon. This extension might add important value mainly in cases with low SARS-CoV-2 load, where RT-qPCR alone can deliver conflicting results.sResultsWe successfully established a combined RT-qPCR and S-gene pyrosequencing method which can be optionally exploited after routine diagnostics or for epidemiologic studies. This allows a more reliable interpretation of conflicting RT-qPCR results in specimens with relatively low viral loads and close to the detection limits of qPCR (CT values >30). After laboratory implementation and characterization of a best practice protocol we tested the combined method in a large pediatric cohort from two German medical centers (n=769). Pyrosequencing after RT-qPCR enabled us to uncover 6 previously unrecognized cases of pediatric SARS-CoV-2 associated diseases, partially exhibiting unusual and heterogeneous presentation. Moreover, it is notable that in the course of RT-qPCR/pyrosequencing method establishment we did not observe any case of false-positive diagnosis when confirmed SARS-CoV-2-positive specimens were used from foregoing routine testing.ConclusionsThe proposed protocol allows a specific and sensitive detection of SARS-CoV-2 close to the detection limits of RT-qPCR. Combined RT-qPCR/pyrosequencing does not negatively affect preceding RT-qPCR pipeline in SARS-CoV-2 diagnostics and can be optionally applied in routine to inspect conflicting RT-qPCR results.