Pitfalls in clinical genetics

With the increasing availability of genetic tests, more doctors are offering and ordering such tests for their patients. Ordering a genetic test appears to be a simple process of filling in paperwork, drawing 3 mL of blood in an ethylenediaminetetraacetic acid tube and receiving a test report. This is identical to sending off a full blood count. However, it is far more complex than that. There are many potential pitfalls, as shown by the increasing number of complaints and lawsuits filed against doctors and allied health staff. Furthermore, clinical genetics involves more than just ordering tests; in fact, focusing on genetic tests alone is a potential pitfall. In this review, we discuss the common pitfalls in clinical genetics and how doctors can avoid these pitfalls to ensure patient safety and to safeguard their practice.

False-Negative Results of Real-Time Reverse-Transcriptase Polymerase Chain Reaction for Severe Acute Respiratory Syndrome Coronavirus 2: Role of Deep-Learning-Based CT Diagnosis and Insights from Two Cases

The epidemic of 2019 novel coronavirus, later named as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is still gradually spreading worldwide. The nucleic acid test or genetic sequencing serves as the gold standard method for confirmation of infection, yet several recent studies have reported false-negative results of real-time reverse-transcriptase polymerase chain reaction (rRT-PCR). Here, we report two representative false-negative cases and discuss the supplementary role of clinical data with rRT-PCR, including laboratory examination results and computed tomography features. Coinfection with SARS-COV-2 and other viruses has been discussed as well.

Value of non-real-time radial probe endobronchial ultrasound guided transbronchial lung biopsy in the diagnosis of peripheral lung cancer and analysis of false negative results / 中国内镜杂志

Objective To explore the diagnostic value of non-real-time radial probe endobronchial ultrasound (RP-EBUS) guided transbronchial lung biopsy (TBLB) for peripheral lung cancer and analysis of false negative results. Methods A retrospective analysis of the clinical and imaging data of 256 patients with peripheral lung cancer between March 2013 and December 2016, all the cases underwent non-real-time RP-EBUS guided TBLB, then evaluate its significance in the diagnosis of peripheral lung cancer and analyze the reasons of false negative results. Result In 256 patients who received non-real-time RP-EBUS examinations, 73.83% (189/256) of peripheral lung cancer were detected by RP-EBUS and the positive rate of RP-EBUS guided TBLB was 61.33% (157/256). The positive rate of non-real-time RP-EBUS guided TBLB was correlated with lesions >2 cm in diameter, lesions close to visceral pleura, ultrasonic image characteristics and the RP-EBUS probe surrounding by lesion (P < 0.05). The positive rate of non-real-time RP-EBUS guided TBLB was not correlated with RP-EBUS probe passed through lesions and times of biopsy (P > 0.05). Complications including bleeding, chest pain and pneumothorax recovered spontaneously. Conclusion Non-real-time RP-EBUS guided TBLB was a practical technology for diagnosis of peripheral lung cancer with high diagnostic rate and good safety. Lesion size, connection to visceral pleura, ultrasonic image characteristics and the RP-EBUS probe surrounding by lesion influenced the diagnostic yield. Improvement of operative skills can reduce false negative results.

Analysis of the influencing factors on the false negative of electrocardiogram treadmill exercise test in pa-tients with coronary heart disease / 中国综合临床

Objective To study the influencing factors on the false negative of electrocardiogram tread?mill exercise test.Methods One hundred and seventy cases coronary heart disease( CHD) patients with coro?nary angiography and carried out electrocardiogram treadmill exercise test from January 2012 to June 2015 in Cardiology Department of the People’ s Hospital of Yanchang County were selected as research objects,including 80 cases of false negative and 90 of positive.The clinical data of two groups were analyzed retrospectively.Results (1)Single factor analysis:CAG results in the false negative group showed that there were 54 cases(67.50%) of single vessel stenosis,14 cases(17.50%) of two vessel stenosis,12 cases(15.00%) of three vessel stenosis,in positive group there were 48 cases(53.33%),34 cases(37.78%) and 8 cases(8.89%) respectively,the differ?ences between the two groups was significant(χ2=8.93,P<0.05).The ST segment of the coronary artery stenosis in the false negative group was 19 cases(23.75%),83 cases (92.22%) in the positive group.There were 61 ca?ses (76.25%) and 7 cases(7.78%) with good collateral circulation in the coronary artery of the two groups,re?spectively,the difference between the two groups was significant(χ2=82.74,P<0.01).There were significant differences in terms of left anterior descending artery(LCX),left anterior descending branch(LAD),left main trunk(LM) diameter between the two groups((3.58±0.95) mm vs. (3.47±0.15) mm,(4.25±0.11) mm vs. (3.94±0.17) mm,(4.58±0.37) mm vs. (4.37±0.26) mm;t=2.91,6.80,2.06;P<0.05).(2)Considering false negative and positive as a dependent variable,and items with significance level including the number of narrow blood vessels,the diameter of coronary artery,LCX,LAD and LM diameters as independent variables in the sin?gle factor analysis,logistic regression analysis was carried out to find that LAD had significant difference in diam?eter,which was independent risk factor for the development of electrocardiogram exercise test false negatives( OR=16.95,95%CI 3.58-80.27,P<0.01).Conclusion False negative is associated with coronary artery diameter for coronary heart disease patients after electrocardiogram treadmill exercise test.The wider coronary diameter is, the easier to produce false negative results in exercise treadmill test.

A Study of False Negative Results of Gelle Test / 听力学及言语疾病杂志

Objective To study the false negative results of Gelle test .Methods Hearing test data between August 2013 to July 2014 were retrieved from outpatient records with hearing complaints of tinnitus or hearing loss . Recruiting criteria:no history of otitis media ,normal tympanic membrane ,no radiologic manifestations of lesions in middle ear and mastoid and abiltly of clear expression of changes of hearing .A total of 60 patients(120 ears ) were tested with conventional pure tone audiometry (PTA) and Gelle test .Acoustic immittance and distortion product otoacoustic emission (DPOAE) were tested in 110 and 113 ears ,respectively .Results Among 120 ears ,7 were di‐agnosed as conductive hearing loss ,23 as mixed hearing loss ,52 as sensorineural hearing loss ,and 38 as normal hearing by pure tone audiometry .The negative Gelle test results were detected in 5 ,11 ,16 and 3 ears ,respective‐ly .110 ears were tested with tympanometry ,types A ,B and C tympanograms were found in 102 ears ,2 ears and 6 ears ,respectively ,and the negative Gelle test results were 22 ,2 and 4 ,respectively .DPOAEs were recordable in 56 ears and negative in 57 ears ,and negative Gelle tests were recorded in 12 and 17 ears respectively .Conclusion False-negative results were found in all types of PTA ,tympanometry and DPOAE .It indicates that Gelle test might not be sensitive and accurate enough to evaluate the integrity and mobility of ossicular chain .Gelle test com‐bined with PTA and DPOAE may be better for assessment of hearing loss and entity of ossicular chain .

Reporting Results of Research Involving Human Subjects: An Ethical Obligation

Researchers have an ethical responsibility to report the results of research involving human subjects. Dissemination of results ensures that patient care is based on good science and that the field of medicine advances based on complete and accurate knowledge. However, current evidence suggests that publication is often neglected or substantially delayed, especially in the case of negative and inconclusive results. Researchers, editors and reviewers should value all high-quality research regardless of the conclusiveness of the results and ensure that all research involving human subjects is registered in a publicly accessible database.

Determinación de resultados negativos asociados a la medicación en pacientes con diagnóstico de trastornos del humor, hospitalizados en el Servicio de Psiquiatría del Hospital Regional de Iquique Dr. Ernesto Torres Galdames, durante el año 2009 / Determination of negative results associated with medication in patients with mood disorders, hospitalized in the Psychiatry Service Units of the Regional Hospital of Iquique Dr. Ernesto Torre Galdames, during the year 2009

Resultados Negativos Asociados a la Medicación (RNM) son eventos cada vez más frecuentes, vinculados a la terapia farmacológica que obstaculiza los objetivos terapeúticos planteados en los pacientes que requieren tratamiento. Esta investigación se realizó en las dependencias del Servicio de Psiquiatría del Hospital Regional de Iquique, cuyo principal objetivo fue la detección de RNM en las fichas clínicas de pacientes con diagnóstico de trastornos del humor hospitalizados durante el año 2009. Los casos fueron estudiados apoyados con la metodología Dáder y la clasificación de los RNM identificados, se realizó de acuerdo al tercer consenso de Granada. El total de casos incluidos fue de 164, de ellos el 38,4 por ciento presentó un RNM principalmente del tipo "seguridad". La distribución de los RNM a través de las variables independientes se concentró en: sexo femenino, edades entre 18 y 44 años, pacientes con polifarmacia y en hospitalizaciones que se prolongaron hasta por 30 días. Para evaluar si están asociadas estas variables con la aparición de un RNM se aplicó la prueba estadística chi-cuadrado, revelándose diferencias estadísticas significativas en polifarmacia y días cama. Se concluye que los factores asociados a la aparición de un RNM en los pacientes con trastornos del humor del servicio de psiquiatría son la polifarmacia y los días que dura su hospitalización.

Negative Results Associated with Medication (NRM) are increasingly frequent events, linked to pharmacological therapies that hinder the therapeutic goals in the patients who require treatment. This investigation was conducted in the psychiatry service units of the regional hospital of Iquique, whose main objective was de detection of RNM in the clinical records of patients diagnosed with mood disorders, hospitalized in 2009. The cases were studied with the Dáder methodology; the classification of identified RNM was performed according to the third Granada consensus. The total number of cases was 164, 38,4 percent of them presented an RNM through the independent variables focused on: female, aged between 18 and 44 years, patients with poly pharmacy and hospitalization which lasted up to 30 days. To asses whether these variables were associated with the appearance of an RNM, chi-square statistic test used, revealed statistically significant differences in polypharmacy and bed days. In conclusion, the factors associated with the appearance of a RNM in patients with mood disorder are: polypharmacy and days of hospitalization.

Hallazgos patológicos en 100 biopsias prostáticas por punción y diagnóstico original de benignidad / Histological findings in 100 NEEDLE prostatic biopsies and original diagnosis of benignity

Introduction. Detailed revision of prostate biopsies with benign alterations may show potentially malignant lesions limited to isolated fields, which may be overviewed in routine analysis. Aim. To exam the morphological alterations in patients with suspicious of prostatic carcinoma and benign diagnosis in needle biopsies. Materials and methods. During 2000-2001, one hundred consecutive patients with first prostate biopsy diagnosed as benign were included. Biopsies were performed by sextants or modified sextants technique. Slides were reviewed by two observers with knowledge of original diagnosis and this was accepted or modified in accordance to the findings found during the review. Results. Patients age ranged between 57 and 79 years old. Nine per cent of biopsies originally diagnosed as benign revealed different potentially malignant lesions, which should be noted due to possible association with carcinoma. In this group, there were five biopsies with atypical small acinar proliferation, three with few isolated glands with xanthomatous cytoplasm, and one with scarce atypical cells in the prostatic stroma. In contrast with Caucasian and Afro-American population, frequency of high grade intraepithelial neoplasia in needle biopsy seems to be very low and this lesion was not found in any of the 100 biopsies reviewed. Some lesions that simulate carcinoma, as atypical basal cell hyperplasia, post-atrophic hyperplasia, and adenosis were diagnosed as benign, and there was none false positive result. Conclusions. A small but significant group of the biopsies originally diagnosed as benign lesions, showed atypical lesions in isolated fields that were overlooked in the routine analysis. It is necessary the urologist to ask for a directed review of the biopsies if clinical and laboratory data strongly suggest prostatic carcinoma. Additional histological cuts, immunohistochemical studies and more than one observer may increase the frequency of detection of potentially malignant lesions.

Introducción. La revisión detallada de las biopsias prostáticas consideradas benignas, en ocasiones puede mostrar cambios histológicos con potencial maligno limitadas a campos aislados, que pueden ser pasadas por alto en la interpretación rutinaria. Objetivo. Examinar las alteraciones morfológicas en pacientes con sospecha de carcinoma prostático con diagnóstico de benignidad en biopsias prostáticas por punción. Material y métodos. En el periodo 2000-2001 se incluyeron 100 pacientes consecutivos cuya primera biopsia se interpretó como benigna. Las biopsias fueron por sextantes, o sextantes modificadas. Se revisaron las laminillas por dos observadores con el conocimiento del diagnóstico original y éste se aceptó o modificó de acuerdo con los hallazgos encontrados. Resultados. La edad varió de 57 a 79 años. Nueve de las 100 biopsias diagnosticadas como benignas revelaron alteraciones histológicas potencialmente malignas que debieron anotarse en el reporte de patología por su posible asociación con carcinoma. Éstas incluyeron cinco biopsias con proliferaciones acinares atípicas, tres con glándulas de aspecto xantomatoso en campos aislados y una con escasas células atípicas en el estroma prostático. En contraste con la población caucásica y afroamericana, la frecuencia de neoplasia intraepitelial prostática en biopsias por punción en nuestra población parece ser muy baja y ninguna de las 100 biopsias mostró esta alteración. Algunas lesiones que simulan carcinoma como la hiperplasia atípica de células básales, la hiperplasia postatrófica y la adenosis fueron reconocidas como benignas, y no hubo ningún resultado falso positivo. Conclusiones. Un porcentaje significativo de las biopsias con el diagnóstico original de patología benigna, mostraron en la revisión dirigida lesiones focales que fueron pasadas por alto en la práctica cotidiana, incluidas algunas con potencial maligno. El urólogo debe solicitar una revisión dirigida en búsqueda de lesiones sugestivas de malignidad si los datos clínicos y de laboratorio sugieren fuertemente la posibilidad de carcinoma. En estos casos, los niveles histológicos adicionales, los estudios inmunohistoquímicos y la revisión por más de un observador podrían incrementar la detección de lesiones potencialmente malignas.