Efficacy of intraoperative neuromonitoring (IONM) and intraoperative indocyanine green videoangiography (ICG-VA) during unruptured anterior choroidal artery aneurysm clipping surgery.

OBJECTIVE: The aim of this study was to investigate the efficacy of intraoperative indocyanine green videoangiography (ICG-VA) and intraoperative neuromonitoring (IONM) to prevent postoperative ischemic complications during microsurgical clipping of unruptured anterior choroidal artery (AChA) aneurysms. METHODS: We retrospectively reviewed the clinical and radiological records of all patients who had undergone microsurgical clipping for unruptured AChA aneurysms at our institution between April 2001 and December 2019. We compared the postoperative complication rate of the group for which intraoperative ICG-VA and IONM were utilized (group B; n=324) with that of the group for which intraoperative ICG-VA and IONM were not utilized (group A; n=72). RESULTS: There were no statistically significant differences in demographic data between the two groups. Statistically significant differences were observed in the rate of overall complications (p=0.014) and postoperative ischemic complications related to AChA territory (p=0.039). All the cases (n=4) in group B who had postoperative infarctions related to AChA territory showed false-negative results of intraoperative ICG-VA and IONM. CONCLUSIONS: Preserving the patency of the AChA is essential to minimize postoperative complications. Intraoperative monitoring tools including ICG-VA and IONM can greatly contribute to lowering complication rates. However, their pitfalls and false-negative results should always be considered.

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.

Three cases of clinically significant inaccurate carboxyhemoglobin measurement.

Background: Clinicians often rely on measurement of carboxyhemoglobin (COHb) to confirm or rule out a diagnosis of carbon monoxide (CO) poisoning. Methods: We report two cases of false negative COHb in patients with CO poisoning and one case of false positive COHb in a patient without CO poisoning. Results: In the first case, a 20-year-old male developed headache, confusion, and near-syncope while operating a gasoline-powered pressure washer in an enclosed space. In the emergency department (ED), his COHb was 1.8%, but this level was disregarded, and he was referred for hyperbaric oxygen. His COHb just before hyperbaric oxygen was 4.1%, and later analysis of his blood collected at ED arrival revealed a COHb of 20.1%. The referral ED blood gas machine calibration and controls were within specification. In the second case, a 45-year-old male presented with several others to the ED with symptoms of CO poisoning after exposure at a conference. All others had elevated COHb levels, but his COHb was 2%. He was discharged but returned shortly with continued symptoms and requested his COHb be repeated. The repeat COHb was 17% (84 minutes after the first). After three hours of oxygen, his COHb was 7%. In the final case, an 83-year-old non-smoking male presented to an ED with breathlessness and tachypnea and was diagnosed with COVID-19 pneumonia. His COHb was 7.1%, but he reported living in an all-electric home. Another adult who lived with him and rode with him to the ED was asymptomatic and had a COHb of 3%. Later, COHb of 1.9% was measured from blood collected at ED arrival, and gas chromatography/mass spectrometry confirmed this result (2%). Conclusions: COHb levels are not always accurate. Clinicians should use clinical judgment to manage their patients, including rejecting laboratory values that do not fit the clinical situation.

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.

False negative point-of-care urine pregnancy tests in an urban academic emergency department: a retrospective cohort study.

STUDY OBJECTIVE: To determine the prevalence of false negative point-of-care (POC) urine pregnancy tests among emergency department (ED) patients and among those with abdominal pain or vaginal bleeding. METHODS: We identified all female patients, ages 14-50 years without prior hysterectomy who had a negative POC urine pregnancy test (beta subunit of human chorionic gonadotropin [ß-hCG]) performed by trained clinical staff in the ED between September 1, 2017 and December 31, 2018, as well as a subgroup we defined a priori as "high risk" for early pregnancy complications based on a triage chief complaint (text) of abdominal pain or vaginal bleeding. We identified those with a positive urine ß-hCG, serum ß-hCG >5 mIU/mL, or a diagnosis of pregnancy within 3 months of the initial ED visit (index visit). We used structured chart review with American College of Obstetrics and Gynecology guidelines to determine pregnancy diagnosis and outcomes (ectopic, intrauterine, abnormal including spontaneous abortion, and unknown), the date of conception, and whether the pregnancy was present at the index visit. RESULTS: Of 10,924 visits with a negative urine pregnancy test result that were screened for a pregnancy outcome, 171 (1.6%, 95% confidence interval [CI] = 1.4, 1.8) had a pregnancy present at the index visit. Diagnoses were ectopic (n = 12, 7.0%), intrauterine (n = 71, 41.5%), abnormal (n = 77, 45.0%), and unknown (n = 11, 6.4%). Of the 2732 patients with high-risk complaints, 97 (3.6%, 95% CI = 2.9, 4.3) had a pregnancy present at the index visit (relative risk of a pregnancy diagnosis 3.9, 95% CI = 2.9,5.3), including 10/12 ectopic (83%), 58/77 abnormal (75%), and 25/71 intrauterine pregnancies (35%). Serum ß-hCG ranged from 2 mIU/mL to above assay (median = 119.5, interquartile range = 957.5). CONCLUSION: Although false negative urine pregnancy tests were uncommon, multiple pregnancy diagnoses were missed, including ectopic pregnancies. False negatives were more common among patients with abdominal pain or vaginal bleeding. Concurrent serum ß-hCG levels demonstrated a broad distribution.

Postoperative cerebral air embolism with delayed abnormal brain MRI findings.

Cerebral air embolism (CAE) is a rare but well-known complication resulting from invasive medical procedures; however, previous studies have not examined the postoperative longitudinal MRI changes in CAE. In particular, the likelihood that such changes may be observed after an initial delay when using magnetic resonance imaging (MRI) has not been explored. We herein report a case of CAE with no MRI abnormalities 4 h after a pulmonary vein isolation (PVI) procedure and where the first abnormality was found 22 h after the procedure. A 65-year-old man underwent PVI for paroxysmal atrial fibrillation and showed no signs of recovery from anesthesia after the procedure; thus, he was transferred to our emergency department for further examination. Neurological examination revealed conjugate eye deviation to the right and quadriplegia. Although initial computed tomography (CT) and MRI revealed no abnormalities, CAE was suspected, and a high-concentration oxygen treatment was administered. MRI performed 22 h after the procedure revealed restricted diffusion affecting the cortical areas. At the same day, he was transferred for hyperbaric­oxygen chamber treatment. After 7 days of treatment, the patient recovered clinically and neurologically. He regained consciousness and was able to communicate. As suggested by this case, CT and MRI findings may fail to reveal CAE abnormalities initially. In such cases, as urgent treatment is necessary, it is important to consider diagnosing CAE based on the patient's history and administering a high concentration of oxygen. Finally, to reach a correct diagnosis, repeated brain MRI should be considered for patients with suspected CAE.

rRT-PCR Results of a Covid-19 Diagnosed Geriatric Patient.

In this study, we aimed to present a geriatric patient with the diagnosis of COVID-19 and with contradictory results in rRT-PCR examinations in short time intervals. A 69-year-old male patient was admitted to the emergency room on the 18th day of May 2020, with the complaints of fever, sweating, myalgia, dry cough that continued for 5 days, and the lack of taste that started on the day he applied to the emergency room. Comorbidity factors include diabetes mellitus, bronchial asthma, and hypertension. The patient has a history of 36 years of smoking 1.5 packs per day. High laboratory findings during hospitalization: monocytes, creatinine, CRP (C-reactive protein). In the thorax CT, in the parenchyma areas of both lungs, there are increases in attenuation with multilobe distributions (more visible at the level of the upper lobes) in the form of ground-glass opacities. May 19, 2020, was subjected to the rRT-PCR test, repeated twice on the 19th of May which also resulted in positive. Despite rRT-PCR tests, which were negative on 27th of May and positive on 28th of May, the patient, whose symptoms disappeared, and general condition improved, was discharged on June 1, 2020, with the recommendation for home isolation. In our case, unlike the incubation period only, we encountered a negative rRT-PCR result on the 8th day after diagnosis. Therefore, the COVID-19 pandemic control and filiation evaluation with the rRT-PCR test may produce false negative results.

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.

[Analysis of factors influencing the false-negative diagnosis of cervical/vaginal liquid based cytology].

Objective: To investigate the possible influencing factors of false-negative diagnosis of cervical/vaginal liquid based cytology, and further improve the sensitivity of cervical/vaginal cytology. Methods: The results of cervical/vaginal cytology of outpatients and inpatients in Department of Obstetrics and Gynecology, Peking University First Hospital from July 2015 to December 2018 were analyzed retrospectively. Cytological false-negative cases were defined as the patients whose cytological results showed no intraepithelial neoplasia and malignant (NILM), but whose biopsy was diagnosed as cervical intraepithelial neoplasia (CIN) 2 or vaginal intraepithelial neoplasia (VAIN) 2 or above within 6 months of the diagnosis. The review of false-negative cytology smear was completed by two senior cytologists. Two-class logistic regression was used to evaluate the influence of age, location or number of lesion, and degree of lesion on the false-negative diagnosis of cytology. The reasons for the inconsistency of false-negative diagnosis were analyzed with the review results. Results: Among 1 009 cases of CIN2+ and VAIN2+ lesions, 180 cases (17.8%) showed NILM. After reviewing the smear, 123 cases (68.3%) were identified as NILM and 57 cases(31.7%) as abnormal. The false-negative rate was the highest (20.8%) in the patients with age≤30 years, and the risk was 8.85 times higher than the patients aged 31 to 60 years (P<0.001), 9.26 times than the patients aged≥60 years (P<0.001). The highest cytological false-negative rate was 50.0% for cervical polyps or intraductal lesions. The false-negative rate of vaginal wall or vaginal pedicle rupture was 13.0%; that of single cervical lesion was 22.3%; that of high-grade squamous intraepithelial lesion(HSIL) and adenocarcinoma in situ of cervix(AIS) was 13.7% and that of malignant lesions was 3.9%. The most common cell types in the reviewed abnormal cases were squamous cells in the middle surface layer (38.6%) and squamous cells in the outer bottom layer (24.6%). The abnormal cells in all smears was the most common distribution (59.7%), the number of abnormal cells in the smear was less than 10 (31.6%), nuclear enlargement and light staining were common (42.2%), and inflammatory lesions or keratotic changes in the background were most common (59.7%). Conclusions: Age of the patient, location or number of lesion, and degree of lesion are associated with false-negative diagnosis of cytology. Summarizing sampling experience and improving sampling skills will help reduce the occurrence of false-negative cases. Cytopathologists should examine slightly abnormal changes more carefully and learn how to further reduce the false-negative rate procactively.

Variplex™ test system fails to reliably detect SARS-CoV-2 directly from respiratory samples without RNA extraction.

Diagnosis of COVID is performed by PCR methods, but their capacity is limited by the requirement of high-level facilities and instruments. The loop-mediated isothermal amplification (LAMP) method has been utilized for the detection of isolated virus-specific RNA. Preliminary data suggest the possibility of isothermal amplification directly from respiratory samples without RNA extraction. All patients admitted to our hospital were screened for SARS-CoV-2 by routine. Respiratory samples were tested by variplex system based on LAMP method directly without RNA extraction and by PCR. Primary endpoint was the false-negative rate of variplex test compared with PCR as gold standard. In 109 patients variplex test and PCR assay were performed simultaneously. Median age was 80 years and male/female ratio was 40/60%. The prevalence of PCR-confirmed COVID diagnosis was 43.1%. Variplex test was positive in 13.8%. False-negative rate of variplex test compared with PCR was 83.0%. The potential of LAMP technology using isolated RNA has been demonstrated impressively by others, and excellent sensitivity and specificity of detecting SARS-CoV-2 has been reported. However, without RNA extraction, the variplex test system failed to reliably detect SARS-CoV-2 directly in respiratory samples.

Breast cancer survivors' risk of interval cancers and false positive results in organized mammography screening.

BACKGROUND: Breast cancer survivors are increasing followed for new breast cancers / recurrences by mammography screening only. We aimed at assessing how often breast cancer survivors get a false positive or false negative result at mammography screening. METHODS: All mammography screenings performed between 2007 and 2017 in the Danish national mammography screening programme were included. Screenings in women with a breast cancer diagnosis prior to invitation were included in the "breast cancer survivors" group, while remaining screenings were included in the "no previous breast cancer" group. We compared the proportion of false positive screenings and the proportion of breast cancers detected at screening among breast cancer survivors and women without previous breast cancer. The analyses were further stratified according to whether the women had a diagnostic breast imaging in the 21 months prior to the screening. RESULTS: At initial screenings, breast cancer survivors had a significant lower false positive risk than other women, while the risk was similar at subsequent screenings. Breast cancer survivors had a significant lower proportion of breast cancers detected at screening compared to other women. This was true both for women who had a diagnostic breast imaging in the 21 months prior to screening and those who did not. CONCLUSION: This study shows that breast cancers survivors have a smaller amount of their new breast cancers detected at mammography screening, when compare to the amount of new breast cancers detected at mammography screening among women without previous breast cancer. The lower sensitivity does not seem to be due to different behavior among breast cancer survivors.

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.

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.

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.

Twenty-eight-day follow-up of patch test reactions to p-phenylenediamine and p-phenylenediamine dihydrochloride: A multicentre study on behalf of the European Environmental and Contact Dermatitis Research Group.

BACKGROUND: There is an ongoing discussion on whether routinely patch testing with p-phenylenediamine (PPD) 1.0% pet. is safe, owing to the risk of patch test sensitization. Late-appearing patch test reactions may reflect patch test sensitization, but may also be attributable to a low degree of pre-existing sensitization. OBJECTIVES: To follow the positive patch test reactions to PPD and its salt PPD dihydrochloride (PPD-DHC) in order to characterize reaction patterns concerning time and dose in PPD-sensitized individuals. METHODS: Volunteers with previous reactions to PPD 1.0% were included and patch tested with PPD and PPD-DHC in equimolar dilution series. There were then seven follow-up visits over a period of 28 days. RESULTS: Twenty-six volunteers completed the study, of whom 23 of 26 (88%) reacted to PPD 1.0%, and 69% reacted to PPD 0.32%. Altogether, 42% and 27% reacted to the corresponding equimolar concentrations of PPD-DHC. After day 7, no new reactions were observed to any concentration tested, either of PPD or of PPD-DHC. CONCLUSION: No late-appearing reactions to PPD or PPD-DHC were observed at any dose. There is a risk of missing contact allergy when the dose is decreased.

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.

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.

Influence of visual field results in the glaucoma diagnosis / Influência dos resultados do campo visual no diagnóstico de glaucoma

Abstract Objective: To determine the influence of visual field results in the diagnosis of glaucoma. Methods: A questionnaire with ophthalmologists was conducted where slides of a digital photograph of the optic disc and computerized visual field exam were presented.(Physicians were instructed to answer whether glaucoma was observed in each of the slides). No other information was given to those examiners. Half of the patients had glaucoma with corresponding visual field, and the other half had physiological cupping and normal visual field. The slides were equally divided between retinography and corresponding visual field (same patient) and exams randomly exchanged, where an optic disc of glaucoma with a normal visual field was placed, and vice-versa. The order in which the slides were presented was also randomized. Results: Forty slides were evaluated by 29 ophthalmologists. No glaucoma specialist was included. The overall agreement among the examiners (Kappa) was 0.270 ± 0.281, and 0.261 ± 0.238 for the exams of the same eye and was 0.274 ± 0.217 from the slides with the exams changed (p=0.4). The diagnosis was made correctly in glaucoma patients with corresponding visual field exam in 66.89% of the cases, and in 66.20% of patients with physiological cupping. When the exams were exchanged, the results dropped to 34.13% and 35.86%, respectively (p<0.001 for both). Conclusion: Visual field results may influence the diagnosis of glaucoma by non-glaucoma specialists.

Resumo Objetivo: Avaliar a influência da campimetria computadorizada no diagnóstico do glaucoma. Métodos: Foi realizado questionário com oftalmologistas apresentando slides com uma fotografia digital de disco óptico e campo visual computadorizado. Os médicos deveriam assinalar se o exames apresentados eram de glaucoma ou não. Nenhuma outra informação foi passada para os examinadores. Metade dos pacientes apresentavam glaucoma com dano correspondente de campo visual, e a outra metade aumento fisiológico da escavação e campo visual normal. Os slides foram igualmente divididos em: retinografia e campo visual correspondentes (mesmo paciente) e exames invertidos de forma aleatória, colocando um disco óptico de glaucoma com um campo visual normal e vice-versa. A ordem de apresentação dos slides foi randomizada previamente. Resultados: Foram incluídos 40 slides, avaliados por 29 oftalmologistas. Nenhum especialista em glaucoma foi incluído. A concordância entre os examinadores (Kappa) foi de 0,270 ± 0,281, sendo de 0,261 ± 0,238 para os exames correspondentes e 0,274 ± 0,217 para os slides com os exames trocados (p=0,4). O diagnóstico foi realizado corretamente nos pacientes com glaucoma com o campo visual correspondente em 66,89% dos casos, e em 66,20% nos pacientes com aumento da escavação (normais). Quando houve a troca da correspondência dos exames, os valores caíram para 34,13% e 35,86%, respectivamente (p<0,001 para ambos). Conclusão: O conhecimento prévio dos resultados do campo visual pode influenciar o diagnóstico do glaucoma.