Addressing the problem of hook effect in sandwich lateral flow immunoassay: review and impact on future solutions / 中华检验医学杂志

Lateral flow immunoassay (LFIA) is a rapid detection technique that allows researchers to move the antigen-antibody reaction from a test tube or laboratory vessel to a test strip. Due to the chromatographic effect of the test strip, the solution would move to a specified direction based on the test and complete the whole antigen-antibody specific reaction. A qualitative judgment can be made with the naked eye by observing the color change of the reagent strip at a specific location. Because of its advantages of being fast, simple, specific, inexpensive, and requiring no specialized personnel, LFIA is now widely used in medical testing, food quality monitoring, environmental monitoring, agriculture and animal husbandry. A major bottleneck for the development of LFIA technology is the hook effect. This paper summarizes the current methods, means and research progresses to combat the hook effect, hoping to provide a strong technical reference for researchers to design test strips, select suitable nanoparticles, and achieve quantitative LFIA detection.

Application value of modified magnetic bead screening for enrichment of cell-free fetal DNA from maternal peripheral blood in non-invasive prenatal testing / 中华围产医学杂志

Objective:To evaluate the value of modified magnetic bead screening for enrichment of cell-free fetal DNA (cffDNA) in non-invasive prenatal testing (NIPT).Methods:This study retrospectively recruited 31 cases with low concentration of cffDNA (<6.00%), Z value in the gray zone (3.00-4.00) at the first detection, or false-positive (confirmed by invasive prenatal diagnosis) or false-negative (confirmed by postnatal chromosome test) results among 11 000 pregnant women who underwent routine NIPT in Beijing Haidian District Maternal and Child Health Care Hospital from October 2017 to December 2019. Plasma samples collected for the first-time routine NIPT were used to enrich cffDNA using modified magnetic beads for NIPT (modified NIPT). Wilcoxon rank sum test was used to compare the modified NIPT with the routine NIPT in detecting the cffDNA concentrations of male fetuses.Results:Among the 31 pregnant women, there were 13 cases with low cffDNA concentration in routine NIPT, 11 having false-positive results in the routine NIPT (three for trisomy 13, four for trisomy 18 and four for trisomy 21, all were confirmed by invasive prenatal diagnosis), six with gray-zone Z values in the first-time NIPT (retesting indicating low risk) and one having false negative result for trisomy 21 (confirmed by postnatal chromosome test). Cell-free DNA (cfDNA) fragments less than 150 bp were effectively enriched using the modified magnetic bead screening and the concentration of cffDNA was increased from 4.43% (2.45%-17.61%) in routine NIPT to 13.46% (7.75%-36.64%) in the modified NIPT ( Z=-14.22, P<0.01). Results of the modified NIPT indicated that 13 cases with low cffDNA concentration of routine NIPT were successfully detected as low risk, as well as the risks in the six cases with gray-zone Z value and six of the 11 false-positive cases in the routine NIPT were low, which were consistent with the retest results of the routine NIPT, while high risk was found in one false-negative case. Conclusions:The modified NIPT could reduce the false positive rate by lowering the failure rate caused by low concentration of cffDNA and is able to identify false-negative cases. Compared with the routine NIPT, it shows a higher success rate and a lower false positive rate.

Analysis of clinicopathologic features of false negative sentinel lymph nodes in patients with endometrial cancer / 国际肿瘤学杂志

Objective:To compare the clinicopathological features of patients with false negative and true negative pathological biopsy of sentinel lymph nodes in endometrial cancer, and to explore the related factors of missed diagnosis of sentinel lymph nodes.Methods:From January 2020 to January 2022, 31 patients underwent sentinel lymph node biopsy combined with systematic lymph node resection in the First Affiliated Hospital of Shandong First Medical University were retrospectively analyzed, of which 2 were false negative and 29 were true negative. PubMed literature on sentinel lymph node false negative of endometrial cancer was searched from the establishment of the database to December 2022, with the search terms "Sentinel lymph node" "Endometrial neoplasms" and "False negative" . A total of 15 cases of false negative patients with similar methods to this study were extracted. In the false negative group, there were 17 false negative patients with sentinel lymph node negative but systemically excised lymph node positive, including 2 cases in our hospital and 15 cases in the literature. The true negative group included 29 true negative patients with negative sentinel and systemic lymph nodes, all from our hospital. The clinicopathologic features of the two groups were compared.Results:There were statistically significant differences in tumor grade ( χ2=6.09, P=0.014) , lymph vascular space invasion ( P=0.012) and myometrial invasion ( χ2=9.66, P=0.002) between the two groups. However, there was no significant difference in histological type between the two groups ( χ2=0.19, P=0.661) . Conclusion:There is a risk of false negative for sentinel lymph node biopsy in patients with endometrial carcinoma with high-grade tumor, myometrial invasion ≥1/2 and lymph vascular space invasion.

False negatives of screening in large-scale population / 上海预防医学

ObjectiveTo explore the changing trend of negative predictive value and number of false negatives in screening tests under the condition of low infection rate of infectious diseases. MethodsAssuming that the population is 20 million， to calculate the negative predictive value， numbers of true negatives and false negatives of the combination of different sensitivity （75.0%， 80.0%， 85.0%， 90.0%， 95.0%， 99.0%） and specificity （90.0%， 95.0%， 99.0%， 99.9%） when the disease infection rate of the population is 0.10%， 1.0% and 5.0% respectively. ResultsWhen the population infection rate is 0.1%， with the screening test sensitivity ≥75.0% and specificity ≥90.0%， the number of true negatives in 20 million people is about 17.98‒19.96 million. When the sensitivity is 75.0%， the negative predictive value is 99.972%‒99.975%， and the number of false negatives is 5 000； When the sensitivity increases to 99.0%， the negative predictive value is 99.999%， and the number of false negatives decreases to 200. When the population infection rate is 1.0%， a screening test with sensitivity ≥75.0% and specificity ≥90.0% can detect about 17.82‒19.78 million true negatives in 20 million population. When the sensitivity is 75.0%， the negative predictive value is 99.720%‒99.748%， and the number of false negatives is 50 000； When the sensitivity increases to 99.0%， the negative predictive value increases to 99.990%， and the number of false negatives decreases to 2 000. When the population infection rate is 5.0%， with sensitivity ≥75.0% and specificity ≥90.0%， the number of true negatives in 20 million people is about 17.10‒18.98 million； when the sensitivity is 75.0%， the negative predictive value is 98.559%‒98.700%， and the number of false negatives can reach 250 000； When the sensitivity is 99.0%， the negative predictive value increases to 99.942%‒99.947%， and the number of false negatives decreases to 10 000. The lower the infection rate of the population， the fewer false negatives will appear in the screening. ConclusionThe number of false negatives in large-scale screenings increases exponentially with the increase of infection rate. Screenings should be carried out as early as possible in a pandemic of infectious diseases， so as to control the spread of the pandemic as soon as possible.

Application of peripheral perfusion index in the screening of congenital heart disease in neonates / 中国小儿急救医学

Congenital heart disease (CHD) is the most common congenital malformations, and critical CHD is one of the main causes of neonatal death and poor prognosis.Early screening and detection of congenital heart disease in newborns is helpful to early intervention and improve prognosis.At present, pulse oximetry alone, pulse oximetry combined with physical examination or pulse oximetry combined with cardiac murmur auscultation in early postnatal screening can detect most of critical CHD, but there are still some false negative results.Peripheral perfusion index (PPI) may have a certain value in finding left ventricular obstructive CHD that can not be found in the current screening methods.Therefore, this review summarized the technical principle and influence factors of PPI, its feasibility and effectiveness in neonatal CHD screening, and the possible threshold of screening, in order to provide a certain basis for PPI screening of neonatal CHD in the future.

HIV nucleic acid results and follow-up of 73 WB negative and indeterminate samples in Dujiangyan area / 中华检验医学杂志

Objective:To test the HIV virus nucleic acid using immunoblot method (Western blotting, WB) and to follow-up with the negative and indeterminate samples in the Dujiangyan area, compare the WB and nucleic acid results before and after followed-up, and try to reduce the WB band′s false-negatives and false-positives.Methods:The 286 suspected HIV infection samples in the Dujiangyan region from January to October 2021 were confirmed by WB, the HIV virus load were tested for the samples that were WB negative and WB indeterminate, those patients were followed-up with epidemiological history and viral load results, and the results before and after tracking were compared.Results:In the 286 samples of suspected HIV infection included in this study, we reported 213 (74.48%) WB positive, 37 WB negative (12.94%), and 36 WB indeterminate (12.58%); 10 of 37 WB negative samples were followed-up; 18 of 36 WB indeterminate samples were followed-up. Among the followed-up WB negative and indeterminate samples, 17 of them had virus nucleic acid detection prior to the follow-up, and all of them turned positive after following-up. The others with no previous virus nucleic acid detection were confirmed to be negative.Conclusions:Among the followed-up samples, 2 samples were false-negative in WB negative results, and 3 were false-positive in WB indeterminate results. The viral nucleic acid must be tested and followed-up in WB negative and indeterminate samples.

Impak Densiti Payudara dalam Pengesanan Kanser Payudara The Impact of Breast Density on Breast Cancer Detection / Jurnal Sains Kesihatan Malaysia

@#The purpose of this research was to identify which category of breast density had higher possibility led to missed breast cancer and incorrect diagnosis. Ethics approval was granted by the Instituitional Research Ethics Committee. A total of 495 mammographic cases were chosen from the Radiology Department, University Kebangsaan Malaysia Medical Centre. All the mammographic cases were grouped into four groups which is true negative, true positive, false positive and false negative. Next, the mammograms were classified according to breast density categories (BI-RADS (a, b, c and d). Logistic regression was used to estimate the odds ratios of a false-positive and false-negative mammograms being associated with each category of breast density. Women with breast density BI-RADS d were four times more likely to have a false-positive mammogram than women with breast density BI-RADS a (odd ratio [OR], 4.27; 95% CI,0.88- 20.67). While women with breast density BI-RADS b and BI-RADS c were almost two times more likely (odd ratio [OR], 1.59, 1.32; 95% CI, 0.29-8.77, 0.25-7.01) to have a false-negative mammogram than women with fatty breast tissue (BI-RADS a). Mammographic image with breast density BI-RADS d has higher possibility to be falsely diagnosed, while mammographic image with breast density BI-RADS b and c have high possibility to miss the cancer. Thus, radiologist should be more cautious when interpreting mammograms with breast density BI-RADS b, c and d, so that the number of missed cancer and falsely diagnosis can be reduced at very early stage. Early detection of breast cancer can increase patients’ survival rate.

Atrial fibrillation diagnosis algorithm based on improved convolutional neural network / 生物医学工程学杂志

Atrial fibrillation (AF) is a common arrhythmia, which can lead to thrombosis and increase the risk of a stroke or even death. In order to meet the need for a low false-negative rate (FNR) of the screening test in clinical application, a convolutional neural network with a low false-negative rate (LFNR-CNN) was proposed. Regularization coefficients were added to the cross-entropy loss function which could make the cost of positive and negative samples different, and the penalty for false negatives could be increased during network training. The inter-patient clinical database of 21 077 patients (CD-21077) collected from the large general hospital was used to verify the effectiveness of the proposed method. For the convolutional neural network (CNN) with the same structure, the improved loss function could reduce the FNR from 2.22% to 0.97% compared with the traditional cross-entropy loss function. The selected regularization coefficient could increase the sensitivity (SE) from 97.78% to 98.35%, and the accuracy (ACC) was 96.62%, which was an increase from 96.49%. The proposed algorithm can reduce the FNR without losing ACC, and reduce the possibility of missed diagnosis to avoid missing the best treatment period. Meanwhile, it provides a universal loss function for the clinical auxiliary diagnosis of other diseases.

Diagnóstico clínico de COVID-19 con pruebas moleculares negativas consecutivas / Clinical diagnosis of COVID-19 with consecutive negative molecular tests

Resumen Una de las dificultades dentro de la pandemia actual por COVID-19 es la poca especificidad y sensibilidad de las pruebas diagnósticas. Distintas sociedades científicas han planteado algoritmos diagnósticos que incluyen pruebas moleculares, síntomas clínicos, pruebas de laboratorio e imágenes. En nuestro medio se utiliza la prueba de RT-PCR, obtenida de lavado nasofaríngeo, aun conociendo sus limitaciones en términos de sensibilidad. Se presenta el caso de un paciente masculino a quien finalmente se le confirma el diagnóstico de COVID-19 a pesar de tener múltiples pruebas moleculares negativas previas.

Abstract One of the difficulties within the current COVID-19 pandemic is the lack of specificity and sensitivity of diagnostic tests. Different societies have proposed diagnostic algorithms that include molecular tests, clinical symptoms, laboratory tests, and diagnostic imaging. In our setting, we use the RT-PCR in nasopharyngeal lavage, even knowing its limitations in terms of sensitivity. In this article, we present the case of a male patient in whom COVID-19 is confirmed even after multiple negative molecular tests.

Dificultades en la detección de genomas del nuevo coronavirus 2 (SARS CoV-2) / Pandemic and social inequiality: the popular neighborhoods of the Buenos Aires suburbs in preventive social isolation

RESUMEN El manejo de las infecciones virales respiratorias, tanto a nivel nacional como a nivel mundial, requiere resultados científicos de calidad. La reacción en cadena de la polimerasa de transcriptasa inversa (rRT-PCR, por su sigla en inglés) es considerada el "patrón de oro" para detectar el genoma del nuevo coronavirus 2 (SARS-CoV-2), agente causal de la enfermedad por el nuevo coronavirus (COVID-19) sobre todo en la fase aguda de la infección. Su uso es controvertido fuera de un contexto de exposición viral. El objetivo del presente trabajo es analizar escollos encontrados durante la detección del genoma del SARS-CoV-2 que pueden producir resultados falsos. Los falsos negativos de rRT-PCR pueden deberse al momento y la eficacia de la toma de la muestra, la congelación, el almacenamiento y la descongelación, y a la inactivación térmica de la virulencia. Además, las señales retardadas de los controles internos invalidan la negatividad. Por otra parte, las muestras con escaso material biológico llevan a conclusiones negativas falsas, por lo que determinar un umbral (número mínimo de células epiteliales) contribuirá a reducirlas. Sin embargo, la mayoría de los kits detectan ADN humano, pero no fueron calibrados para cuantificar carga celular. Los ácidos ribonucleicos nucleares (ARN) virales adheridos a guantes, tubos y gorros, -entre otros elementos-, son fuente de falsos positivos. Las farmacopeas sugieren que la contaminación externa se controle en series de 100 muestras con al menos una representatividad del 10%. Si se extrapola esta aproximación al laboratorio de análisis clínicos, en lugar de uno se deberían procesar al menos 10 controles negativos contiguos a 10 positivos cada 100 pruebas. Mejorar la detección por rRT-PCR implica un aumento de al menos 20% en el costo de los reactivos, por lo que se necesitan recursos adicionales.

ABSTRACT Emerging respiratory viral infections like the severe coronavirus disease (CoVID 19) caused by novel coronavirus 2 (SARS-CoV-2) require quality results for science-based responses. The reverse transcriptase polymerase chain reaction (rRT-PCR) is considered the gold standard for detecting SARS-CoV-2 (particularly in the acute phase of infection). The aim of the present work was to analyze pitfalls during the search of viral genomes. False negative conclusions are result of sampling timing, performances of swabbing, storage, and thawing and heat-infectivity inactivation. Samples with low biologic material also lead to false negatives. Qualitative controls to detect the presence of human DNA are available in several kits but they were not calibrated for quantification of human cell loads. Moreover, negativity cannot be reported for samples with delayed signals for the internal control (due to deficiency in extraction and/or retro transcription and/or or to the presence of rRT-PCR inhibitors). The viral RNA that may have stick on gloves, on tubes, caps, etc. may produce false positives. The International Pharmacopoeias recommend for external contamination to test at least 10% of the samples. Couples of 10 negative contiguous to 10 positive controls randomly distributed should be therefore included in each series of 100 rRT-PCR tests. These improvements increase the cost of each determination (at least by 20% only for the reactants) and require additional resources.

Nonspecific benign pathological results on computed tomography-guided lung biopsy: A predictive model of true negatives

Objective: The aim of this study is to develop a predictive model for identifying true negatives among nonspecific benign results on computed tomography-guided lung biopsy. Materials and Methods: This was a single-center retrospective study. Between December 2013 and May 2016, a total of 126 patients with nonspecific benign biopsy results were used as the training group to create a predictive model of true-negative findings. Between June 2016 and June 2017, additional 56 patients were used as the validation group to test the constructed model. Results: In the training group, a total of 126 lesions from 126 patients were biopsied. Biopsies from 106 patients were true negatives and 20 were false-negatives. Univariate and multivariate logistic regression analyses were identified a biopsy result of “chronic inflammation with fibroplasia” as a predictor of true-negative results (P = 0.013). Abnormal neuron-specific enolase (NSE) level (P = 0.012) and pneumothorax during the lung biopsy (P = 0.021) were identified as predictors of false-negative results. A predictive model was developed as follows: Risk score = −0.437 + 2.637 × NSE level + 1.687 × pneumothorax - 1.82 × biopsy result of “chronic inflammation with fibroplasia.” The area under the receiver operator characteristic (ROC) curve was 0.78 (P < 0.001). To maximize sensitivity and specificity, we selected a cutoff risk score of −0.029. When the model was used on the validation group, the area under the ROC curve was 0.766 (P = 0.005). Conclusions: Our predictive model showed good predictive ability for identifying true negatives among nonspecific benign lung biopsy results

Analysis of false negative results in throat swab nucleic acid test of severe acute resporatory syndrome coronavirus 2 / 第二军医大学学报

Objective To investigate the false negative rate of throat swab nucleic acid test of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and to analyze the causes, so as to provide references for the prevention and control of coronavirus disease 2019 (COVID-19) in China. Methods A retrospective analysis was conducted on the throat swab nucleic acid test results of 1 452 COVID-19 patients admitted to Guanggu Branch of Maternity and Child Healthcare Hospital of Hubei Province from Feb. 19 to Mar. 20, 2020. The negative results before positive results at discharge were judged as false negative results, and the false negative rate was calculated. The discharged patients were followed up to screen for the patients who were positive for nucleic acid test again, and the relationship between the times of consecutive negative nucleic acid tests before discharge and the positive again results was analyzed. Results Among the 1 452 COVID-19 patients, 592 (40.77%) were males and 860 (59.23%) were females. A total of 212 cases (14.60%) had false negative results. Twenty-eight cases (1.93%) were discovered nucleic acid positive again after discharge. Among the 918 patients whose nucleic acid tests were negative for two consecutive times, 24 (2.61%) were positive again, which was significantly higher than that of the patients whose nucleic acid tests were negative for three consecutive times (0.75%, 4/534; χ2=6.21, P=0.012 7). Conclusion The throat swab nucleic acid test of SARS-CoV-2 has a certain proportion of false negative results, which is one of the reasons for COVID-19 patients are found nucleic acid positive again after discharge. Multiple and continuous tests by different testers are recommended before discharge, and negative nucleic acid test for three or more consecutive times can reduce the incidence of nucleic acid positive results again after discharge.

Analysis of false-negative results for 2019 novel coronavirus nucleic acid test and related countermeasures / 中华检验医学杂志

In December 2019, a cluster of patients with pneumonia of unknown cause were linked to a seafood wholesale market in Wuhan, China. Some studies found that the virus was a new kind of virus which had never been found in the human body. Then, the virus was named 2019 Novel Coronavirus (2019-nCoV) by the World Health Organization (WHO). 2019-nCoV nucleic acid detection is one of the essential indicators of NCP (Novel Coronavirus Pneumonia). Recently, some false-negative cases in China-Japan Friendship Hospital and Hangzhou Hospital led the clinical doctors to question the value of the nucleic acid detection. In this paper, more than 3 000 results of 2019-nCoV detection in Zhongnan Hospital, Wuhan University were analyzed. Attention should be paid to the root cause of false-negative results and the related countermeasures should be taken.

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.

False negative non-invasive prenatal screening result for trisomy 18: a case report / 中华围产医学杂志

We hereby reported a case of false negative non-invasive prenatal screening (NIPS) for trisomy 18. The fetus with increased nuchal translucency (3.2 mm) detected by ultrasound scan at 13+4 gestational weeks received NIPS and the result was negative in chromosomes 21, 18 and 13. A routine ultrasound examination at 22 weeks of gestation revealed multiple anomalies and a second NIPS was offered, which showed a negative result again. The pregnancy was terminated at 22+3 weeks. Multiple fetal and placental biopsies were collected for chromosome analysis using copy number variation sequencing based on high-throughput sequencing and fluorescence in situ hybridization. The fetal karyotype was shown to be 47,XY,+18 in fetal tissues (skin and liver) and umbilical cord, while no chromosomal abnormalities was detected at or near the center of the fetal and maternal surface of the placenta. Results of the chromosomal analysis along the edges of the fetal and maternal surfaces of the placenta were Chr18:47,XY,+18[60]/46,XY[40] and Chr18:47,XY,+18[35]/46,XY[65], respectively. We inferred that placental mosaicism was the cause of the false negative NIPS result. Therefore, genetic counseling before and after NIPS is necessary. Follow-up ultrasound is important for NIPS-negative patients. Invasive prenatal diagnosis is recommended when abnormal ultrasound markers with possible genetic etiology were recognized.

Is the frozen section examination for sentinel lymph node necessary in early breast cancer patients?

PURPOSE: Sentinel lymph node (SLN) biopsy (SLNB) is widely performed for axillary staging in patients with breast cancer. Based on the results of frozen section examination (FSE), surgeons can decide to continue further axillary dissections. This study aimed to verify the accuracy of FSE for SLNs. METHODS: We reviewed the records of 4,219 patients who underwent SLNB for primary invasive breast cancer between 2007 and 2016 at the Severance Hospital. We evaluated factors associated with the false-negative results of FSE for SLNs using the Generalized Estimating Equations model. RESULTS: A total of 1,397 SLNs from 908 patients were confirmed to be metastatic. Seventy-one patients (1.7%) had confirmed pathologic N2 or N3 stage. Among metastatic SLNs, micrometastasis was found in 234 (16.8%). The overall accuracy of SLNB was 98.5%. The sensitivity and false-negative rate of FSE were 86.4% and 13.6%, respectively. Several clinicopathological factors, including the size of SLN metastases, suspicious preoperative axillary lymph nodes, and luminal B subtype, were associated with a higher rate of false-negative results. CONCLUSION: Most patients were not indicated for axillary lymph node dissection. Some patients may show transition in their permanent pathology due to the size of the metastatic node. However, the false-negative results of FSE for SLNs based on the size of the metastatic node did not change our practice. Therefore, intraoperative FSE for SLN should not be routinely performed for all breast cancer patients.

The adequate number of lymph node dissection in pancreatic cancer radical surgery based on nodal staging score(with four-center cohort validation) / 中国实用外科杂志

OBJECTIVE: To estimate the number of lymph nodes(LNs)needed to be examined for adequate LN staging via nodal staging score(NSS).METHODS: A model was fitted based on 3989 pN + patients with resected primary pancreatic adenocarcinoma in the Surveillance,Epidemiology and End RESULTS:(SEER)database.The number of nodes to examine to achieve an N SS of 90% was used as the optimal number.The results were validated in node negative patients from the SEER cohort(2583 patients)and a local multicenter cohort(93 patients).RESULTS: Tumor size is a determinant for the extent of lymphadenectomy.According to the tumor size<2 cm and ≥2 cm,15 and 20 LNs would need to be examined to achieve90% confidence in a pN0 patient.As a result of missing node-positive case,the prevalence of nodepositive was adjusted from 60.7% to 71.0%.In the survival analysis,more LNs examined was shown to be correlated with better prognosis in patients with tumor ≥2 cm.CONCLUSION: The minimum number of LNs for adequate staging depends on the tumor size.The estimation provides a practical standard for evaluating the extent of LN yield for surgeons.

Fatal Cryptococcus gattii meningitis with negative cryptococcal antigen test in a HIV-non-infected patient

Cryptococcus gattii predominantly causes central nervous system and pulmonary infection in both immunocompromised and immunocompetent patients with substantial morbidity. We report a case of rapidly fatal meningitis by C. gattii in an HIV–non-infected man with CD4 lymphopenia who tested negative for cryptococcal antigen. This case may serve as an alert to its wider occurrence and less explored risk factors.

Risk Factors for a False-Negative Result of Sentinel Node Biopsy in Patients with Clinically Node-Negative Breast Cancer / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Although sentinel lymph node biopsy (SLNB) can accurately represent the axillary lymph node (ALN) status, the false-negative rate (FNR) of SLNB is the main concern in the patients who receive SLNB alone instead of ALN dissection (ALND). MATERIALS AND METHODS: We analyzed 1,886 patientswho underwent ALND after negative results of SLNB, retrospectively. A logistic regression analysis was used to identify risk factors associated with a false-negative (FN) result. Cox regression model was used to estimate the hazard ratio of factors affecting disease-free survival (DFS). RESULTS: Tumor located in the upper outer portion of the breast, lymphovascular invasion, suspicious node in imaging assessment and less than three sentinel lymph nodes (SLNs) were significant independent risk factors for FN in SLNB conferring an adjusted odds ratio of 2.10 (95% confidence interval [CI], 1.30 to 3.39), 2.69 (95% CI, 1.47 to 4.91), 2.59 (95% CI, 1.62 to 4.14), and 2.39 (95% CI, 1.45 to 3.95), respectively. The prognostic factors affecting DFS were tumor size larger than 2 cm (hazard ratio [HR], 1.86; 95% CI, 1.17 to 2.96) and FN of SLNB (HR, 2.51; 95% CI, 1.42 to 4.42) in SLN-negative group (FN and true-negative), but in ALN-positive group (FN and true-positive), FN of SLNB (HR, 0.64; 95% CI, 0.33 to 1.25) did not affect DFS. CONCLUSION: In patients with risk factors for a FN such as suspicious node in imaging assessment, upper outer breast cancer, less than three harvested nodes, we need attention to find another metastatic focus in non-SLNs during the operation. It may contribute to provide an exact prognosis and optimizing adjuvant treatments.

False-negative reactions to the comparative intradermal tuberculin test for bovine tuberculosis / Reações falso-negativas ao teste cervical comparativo para tuberculose bovina

According to the Brazilian National Program for the Control and Eradication of Animal Brucellosis and Tuberculosis (PNCEBT), the routine tests for the diagnosis of bovine tuberculosis in the country are the simple intradermal tuberculin test (SITT) of the Ministry of Agriculture, Livestock and Food Supply (MAPA), the caudal fold test and the comparative intradermal tuberculin test (CITT). The latter is also used as a confirmatory test. A group of 53 animals from three dairy herds in a focal area for bovine tuberculosis, that were submitted to depopulation in the state of Rio Grande do Sul, were submitted to the CITT. Tissues were cultured and the resulting colonies were confirmed by PCR and DNA sequencing. Among the 53 animals analyzed using the CITT, 32 (60.4%) were negative, 14 (26.4%) were positive and seven (13.2%) results were inconclusive. The CITT detected 11 of the 39 animals with culture-confirmed M. bovis infection as positive. Among the total of 14 uninfected animals based on cultures, the CBT detected eight as negative. Thus, the CITT demonstrated sensitivity of 28.2% and specificity of 57.1% for the population sampled. A total of 24/32 (75.0%) of the animals with negative CITT results were culture positive (confirmed by PCR) and were considered false negatives based on the CITT. The maintenance of these false-negative animals in herds has serious implications for the control of the disease, since they can be a source of infection. The addition of complementary tests could help identify such animals and increase the odds of diagnostic success.(AU)

No Brasil, segundo o Programa Nacional de Controle e Erradicação da Brucelose e Tuberculose Animal (PNCEBT), do Ministério da Agricultura, Pecuária e Abastecimento (MAPA), os testes de rotina para o diagnóstico de tuberculose bovina são o teste cervical simples (TCC), o teste da prega caudal (TPC) e o teste cervical comparativo (TCC), sendo que o último também é utilizado como teste confirmatório. Um grupo de 53 animais oriundos de três rebanhos leiteiros de área de foco para tuberculose bovina que foram submetidos a vazio sanitário no Rio Grande do Sul foi submetido ao TCC. Os tecidos destes animais foram cultivados e as colônias resultantes confirmadas por PCR e sequenciamento de DNA. Dos 53 animais analisados no TCC, 32 (60,4%) foram negativos, 14 (26,4%) positivos e sete (13,2%) inconclusivos, com base no PNCEBT. O TCC detectou como positivos 11 dos 39 animais com infecção por M. bovis confirmada por cultivo. Do total de 14 animais não infectados, baseado na cultura, o TCC detectou oito como negativos. Assim, o TCC apresentou, para a população amostrada, sensibilidade de 28,2% e especificidade de 57,1%. Um total de 24/32 (75,0%) dos animais negativos ao TCC foi positivo no cultivo (confirmado por PCR), sendo considerados falso-negativos ao TCC. A manutenção destes animais falso-negativos nos rebanhos tem sérias implicações para o controle da enfermidade, já que os mesmos podem ser fonte de infecção. A adição de testes complementares poderia auxiliar na identificação destes animais, aumentando a cobertura diagnóstica.(AU)