Long-term follow-up of a series of 24 congenital CMV-infected babies with false negative amniocentesis.

BACKGROUND: Congenital CMV infection is the most common congenital infection worldwide and a major cause of neurological impairment and sensorineural hearing loss. Fetal CMV infection is confirmed by a positive PCR test in the amniotic fluid (amniocentesis performed after 18-20 weeks of gestation and at least 8 weeks after maternal infection). However, despite a negative antenatal CMV PCR result, some newborns can be tested positive at birth. Although not widely documented, the prognosis for these babies appears to be good. OBJECTIVES: The aim of this study is to evaluate the long-term prognosis of fetuses with a false-negative AFS for cCMV, with a minimum follow-up period of 6 years. STUDY DESIGN: This is a retrospective cohort study of false-negative amniocentesis reported at the CUB-Hôpital Erasme and Hôpital CHIREC in Brussels between 1985 and 2017. RESULTS: Of the 712 negative CMV PCR amniocenteses, 24 had a CMV PCR positive at birth. The false negative rate was 8.6 %. Of the 24 cases, 9 primary maternal infections occurred in the first trimester, 14 in the second trimester and 1 in the third trimester. Among the 24 children, 2 had symptoms at birth (hyperbilirubinemia and left paraventricular cysts), but all had normal follow-up (minimum 4 years, mean 16,6 years). DISCUSSION: Only 2 cases could be explained by early amniocentesis. Among the others, the false-negative results could be attributed to a low viral load, a delayed infection or, less likely, to a sample degradation. CONCLUSION: Despite the false-negative results, all 24 children had a normal long-term follow-up.

The features associated with mammography-occult MRI-detected newly diagnosed breast cancer analysed by comparing machine learning models with a logistic regression model.

PURPOSE: To compare machine learning (ML) models with logistic regression model in order to identify the optimal factors associated with mammography-occult (i.e. false-negative mammographic findings) magnetic resonance imaging (MRI)-detected newly diagnosed breast cancer (BC). MATERIAL AND METHODS: The present single-centre retrospective study included consecutive women with BC who underwent mammography and MRI (no more than 45 days apart) for breast cancer between January 2018 and May 2023. Various ML algorithms and binary logistic regression analysis were utilized to extract features linked to mammography-occult BC. These features were subsequently employed to create different models. The predictive value of these models was assessed using receiver operating characteristic curve analysis. RESULTS: This study included 1957 malignant lesions from 1914 patients, with an average age of 51.64 ± 9.92 years and a range of 20-86 years. Among these lesions, there were 485 mammography-occult BCs. The optimal features of mammography-occult BC included calcification status, tumour size, mammographic density, age, lesion enhancement type on MRI, and histological type. Among the different ML models (ANN, L1-LR, RF, and SVM) and the LR-based combined model, the ANN model with RF features was found to be the optimal model. It demonstrated the best discriminative performance in predicting mammography false- negative findings, with an AUC of 0.912, an accuracy of 86.90%, a sensitivity of 85.85%, and a specificity of 84.18%. CONCLUSION: Mammography-occult MRI-detected breast cancers have features that should be considered when performing breast MRI to improve the detection rate for breast cancer and aid in clinician management.

Accuracy of sentinel lymph node biopsy in male breast cancer: Systematic review and meta-analysis.

BACKGROUND: Sentinel lymph node biopsy (SLNB) is commonly used in the surgical management of male breast cancer. Contrary to female breast cancer, limited data exist about its performance in male breast cancer. The objective of this systematic review and meta-analysis was to evaluate the SLNB accuracy in male breast cancer. METHODS: MEDLINE, EMBASE, Web of Science and The Cochrane Library were searched from January 1995 to April 2023 for studies evaluating the SLNB identification rate and false-negative rate in male breast cancer with negative preoperative axillary evaluation and primary surgery. For SLNB false-negative rate, the gold standard was the histology of axillary lymph node dissection (ALDN). Methodological quality was assessed by using the QUADAS-2 tool. Pooled estimates of the SLNB identification rate and false-negative rate were calculated. Heterogeneity of the pooled studies was evaluated using I2 index. RESULTS: A total of 12 retrospective studies were included. The 12 studies that reported the SLNB identification rate gathered a total of 164 patients; the 5 studies that reported the SLNB false-negative rate gathered a total of 50 patients with a systematic ALND. The pooled estimate of the SLNB identification rate was 99.0%. The SLNB false-negative rates were 0% in the 5 included studies and consequently so as the pooled estimate of the false-negative rate with no heterogeneity. CONCLUSION: SLNB for male breast cancer, following negative preoperative axillary assessment and primary surgery, appears feasible, consistent, and effective. Our research supports conducting immediate SLNB histological evaluation to facilitate prompt ALND in case of positive results.

False negative breast cancers on imaging and associated risk factors: a single institution six-year analysis.

PURPOSE: Mitigating false negative imaging studies remains an important issue given its association with worse morbidity and mortality in patients with breast cancer. We aimed to identify risk factors that predispose to false negative breast imaging exams. METHODS: In an IRB-approved, HIPAA compliant retrospective study, we identified all patients who were diagnosed with breast cancer within 365 days of a negative imaging study assessed as BI-RADS 1-3 between January 1, 2014 and January 31, 2020. A matched cohort based on mammographic breast density was created from randomly selected studies with BI-RADS 4-5 designation that yielded breast cancer at pathology within the same time frame. Patient and cancer characteristics, prior personal history of breast cancer and gene mutation status were collected from patient charts. Pearson chi-squared and Student's t-test on two independent groups with significance at < 0.05 was used for statistical analysis. RESULTS: We identified 155 false negative studies of 129 missed cancers and 128 breast density matched true positive cancers. False negative studies were screening mammograms in 57.42% (89/155), diagnostic mammograms in 29.68% (46/155), ultrasounds in 6.45% (10/155) and MRIs in 6.45% (10/155). Rates of personal (41.09% vs. 18.75%, p < 0.001) and family history of breast cancer (68.22% vs. 49.21%, p = 0.002) were higher in the false negative cohort and remained significant when asymptomatic MRI-detected cancers were removed. CONCLUSION: Our findings suggest that supplemental screening may be useful in breast cancer survivors.

Clipping a Positive Lymph Node Improves Accuracy of Nodal Staging After Neoadjuvant Chemotherapy for Breast Cancer Patients, but Does It Drive Management Changes?

BACKGROUND: Sentinel lymph node (SLN) biopsy for cN+ breast cancer patients after neoadjuvant chemotherapy (NAC) is controversial because the false-negative rate (FNR) is high. Identification of three or more SLNs with a dual tracer improves these results, and inclusion of a clipped lymph node (CLN) (targeted axillary dissection [TAD]) may be even more effective. METHODS: A retrospective, single-institution analysis of consecutive cN+ patients undergoing NAC from 2019 to 2021 was performed. Patients routinely underwent placement of a clip in the positive lymph node before NAC, and TAD was performed after completion of therapy. RESULTS: The study analyzed 73 patients, and the identification rate for CLN was 98.6% (72/73). A complete response in the lymph nodes was achieved for 43 (59%) of the 73 patients. Overall, the CLN was not a SLN in 18 (25%) of 73 cases, and for women who had one or two and those who had three or more SLNs identified, this occurred in 11 (32%) and 7 (21%) of 34 cases, respectively. Failure of SLN or TAD to identify a positive residual lymph node status after NAC occurred in 10 (15%) of 69 and 2 (3%) of 73 cases, respectively (p = 0.01). In four cases, a SLN was not retrieved (5.5%), and two of these cases had a positive CLN. In three cases, the CLN was the only positive node and did not match with a SLN, directing lymphadenectomy and oncologic management change in two cases. Therefore, 7 (10%) of 73 cases had a change in surgical or oncologic management with TAD. CONCLUSIONS: For a conservative axillary treatment in this setting, TAD is an effective method. It is more accurate than SLN alone and allows management changes. Further studies are warranted.

The Utility of ACR TI-RADS in Predicting False-Negative Fine Needle Aspiration for Thyroid Cancer.

BACKGROUND: Thyroid nodule fine needle aspiration (FNA) biopsies are associated with a low false-negative rate. There is limited data regarding the predictive value of American College of Radiology Thyroid Imaging Reporting and Data System for false-negative FNA. METHODS: This single-center retrospective study evaluated 119 patients who underwent thyroidectomy. The association of TR category, along with other clinical variables, with false-negative FNA was evaluated. RESULTS: The overall false-negative rate of FNA was 10.8% (n = 9). False-negative FNAs were associated with younger age (mean 42 years vs 50.6 years, P = .04), larger nodule size (mean 4.4 cm vs 3.2 cm, P = .03), and a lower TR category (median 3 v 4, P = .01). DISCUSSION: Lower TR category, younger age, and larger nodule size were associated with false-negative FNA of thyroid nodules. These findings should be taken into context when counseling patients with thyroid nodules who have a benign FNA.

Sensitivity and specificity of SS-OCT for detecting macular pathologies vs SD-OCT.

PURPOSE: To evaluate the sensitivity and specificity of swept-source optical coherence tomography (SS-OCT) biometer compared with the gold standard spectral-domain optical coherence tomography (SD-OCT) for detecting macular pathology in patients with cataract. SETTING: Eye Centers of Tennessee, Crossville, TN. DESIGN: Prospective, cross-sectional, observational, examiner-masked. METHODS: The study included 132 participants aged 50 years and older, who underwent precataract surgery work-up. All participants underwent fixation check retinal scans using SS-OCT biometer (IOLMaster 700) as well as full macular scans using Cirrus SD-OCT. 3 independent masked examiners evaluated the scans if they were normal or had a suspected pathology. Different measures of diagnostic accuracy were calculated for 3 examiners. RESULTS: True positive rate (sensitivity) ranged from 71.1% (32/45) to 79.2% (42/53), and false negative rate was between 20.8% (11/53) and 28.9% (13/45) for the 3 examiners. True negative rate (specificity) ranged from 86.8% (59/68) to 94.1% (64/68), and false positive rate was between 5.9 (4/68) and 13.2% (9/68). The fitted receiver operating characteristic area ranged from 0.83 to 0.95. CONCLUSIONS: Using retinal SS-OCT biometer scans as a replacement of the dedicated macular SD-OCT for screening or diagnosing macular health would not be appropriate because of its low sensitivity. SS-OCT biometer may potentially fail to identify approximately one-fourth of patients who actually have the disease. Therefore, the final decision on macular health should be based on the gold standard SD-OCT scans. When full macular SD-OCT scans are not accessible, the limited retinal scan information from SS-OCT biometer may still provide useful insights into the macular health.

Comparison of Two Shiga Toxin-producing Escherichia coli (STEC) Isolation Protocols in Raw Cow's Milk Cheese Enrichment Broths: Direct STEC Isolation Versus Techniques Based on Immuno-concentration.

The presence of Shiga toxin-producing Escherichia coli (STEC) in dairy products made with raw milk is a major concern for food safety authorities and industries. Two approaches have been proposed to isolate STEC from food. In the IC-Protocol (immuno-concentration protocol), specific serogroups are identified in the enrichment broth after the detection of the stx and eae genes. An immuno-concentration of the targeted serogroups is performed before isolating them on specific media. In the DI-Protocol (direct isolation protocol), a direct isolation of all STEC present in the enrichment broth is carried out after the detection of stx genes. We compared the ability of these two methods to isolate STEC O26:H11, O103:H2, O111:H8, O145:H28, and O157:H7 after artificial inoculation in four different raw milk cheeses. Across all serogroups and cheese types, STEC were isolated in 83.3% of samples when using the IC-Protocol but only 53.3% of samples with the DI-Protocol. For two cheese types, the DI-Protocol failed to isolate STEC O157:H7 strains altogether. Our results suggest that IC-Protocol is a robust methodology to effectively isolate STEC across a range of cheese types.

Low-cost solutions incorporated in a standard surgical pathway for early breast cancer: A pilot study.

We present the results of incorporation of low-cost solutions to provide a standard surgical care for early breast cancer (EBC) patients. This surgical pathway consists of a low-cost vacuum-assisted core needle biopsy, sentinel lymph node biopsy (SLNB) using low-cost methylene blue and fluorescin dyes under local anesthesia and oncoplastic breast surgery. Patients assessed as clinically node-negative axilla underwent such treatment. SLNB using low-cost dyes was performed without any complication. Oncoplastic surgical techniques were opted for in 32 patients, and the lumps were all excised with a ∼1-cm all-around margin on the final histopathological examination. Standard breast cancer surgery can be provided in low-resource settings to eligible EBC patients with low-cost solutions.

Risk of thyroid carcinoma in patients treated surgically with assumed benign cytology in Riyadh, Saudi Arabia.

Objectives: This study aimed to report the rate of thyroid malignancy in benign fine-needle aspirations (Bethesda II) at King Abdulaziz Medical City and evaluate the factors that affect false-negative outcomes of FNA. Methods: All patients referred for thyroidectomy from 2009 to 2019 were reviewed (n = 1968). Only patients with a benign FNA, corresponding to the Bethesda II, were included (n = 384). Information on age, gender, body mass index (BMI), serum thyroid-stimulating hormone, type of surgery and histopathological outcomes were retrieved. Results: Of the sample (n = 384) with an initial benign FNA, 63 patients had a malignancy on postoperative pathological examination, yielding an overall false-negative rate of 16.4%. The most frequently reported histopathological type was papillary thyroid microcarcinomas (n = 52). For the false-negative group, the mean age was 43.8 years (range 21-70 years) with an 84.1% female predominance. The surgical choice for 74% (n = 46) of cases was total thyroidectomy. Age, gender, thyroid function and BMI did not affect the false-negative rate of benign FNA (p > 0.05). Conclusions: This study found a higher risk of malignancy compared to the literature related to benign FNA. The risk of malignancy should be considered, even with benign FNA.

Indeterminate mycobacterium tuberculosis QuantiFERON post Moderna mRNA Covid-19 vaccination.

We report an interesting case of an indeterminate MTB QuantiFERON for a 26-year-old healthy soldier planned for a routine field exercise to Brunei. Further medical history revealed that the patient had a Moderna mRNA Covid-19 vaccine the day before his MTB QuantiFERON test. The patient was subsequently asked to repeat a T-spot test which was non-reactive, there were no longer any issues with the positive control for the T-spot test. Current Covid-19 research suggests that infection causes a dysregulation of the immune system, perhaps this might also be extrapolated where a Covid-19 vaccine might provoke an immune response which might interfere with some immunological assays. In summary there should be more research invested into the immunological interactions that the newly developed Covid-19 vaccinations have with our existing immunological tests such as QuantiFERON tests which forms a key cornerstone in our fight against tuberculosis.

Rates of False-Negative Screening in Prostate Specific Antigen Secondary to 5-Alpha Reductase Inhibitor Usage: A Quality-Improvement Initiative.

PURPOSE: Patients often take 5-alpha reductase inhibitors (5-ARIs) for the management of benign prostatic hyperplasia. However, 5-ARIs can decrease prostate specific antigen (PSA) by approximately half and therefore may lead to false negative PSA tests. We investigated false-screening rates in men on 5-ARIs undergoing PSA testing and whether ordering physicians noticed false negative findings. MATERIALS AND METHODS: A single institution, retrospective study was conducted on patients with a PSA value documented between 2014 and 2017. Patient demographics, PSA results, 5-ARI usage, and providing clinician characteristics were collected. Published normal PSA values were used to determine PSA test positivity; values for those on 5-ARIs were doubled. RESULTS: A total of 29,131 men were included. 1,654 (5.7%) were prescribed 5-ARIs at least 12 months prior to PSA evaluation. 118 men (7.1%) had a value that would be positive if corrected for 5-ARI usage, 33 (27.9%) of which had no indication that the provider had noted this. There was no effect on rates of false negative values if the PSA was ordered by a different provider than the one who prescribed the 5-ARI (p = 0.837). However, if the provider who ordered the PSA test was an urologist, the likelihood that a false negative value would be identified was lower (p=0.001). CONCLUSIONS: More than a quarter of men with false negative tests were missed. This occurred more often when the ordering provider was not an urologist. An educational opportunity exists to improve the quality of PSA testing by preventing false negative tests.

[Covid-19: Thomas Bayes warns and we should listen. False negatives and the probability of encountering them.] / Covid-19: Thomas Bayes ammonisce e noi dovremmo ascoltarlo. I falsi negativi al test e la probabilità d'incontrarli.

We believe that a high percentage of covid-19 infections could be due to the presence of false negative (FN) individuals on rapid swabs. To support this hypothesis and quantify their number, we performed simulations using Bayes' rule and various assumptions about the sensitivity, specificity of swabs and prevalence of infection. Imagining FNs in liberty, we then calculated the probability of encountering them in groups of people with a typical number of habitual sites, such as: bus, supermarket, theatre, etc. The probability of encountering FN from rapid tests was more than 3 times higher (345% change) that reported by the RT-PCR test.

SARS-CoV-2 antigen lateral flow tests for detecting infectious people: linked data analysis.

OBJECTIVES: To investigate the proportion of lateral flow tests (LFTs) that produce negative results in those with a high risk of infectiousness from SARS-CoV-2, to investigate the impact of the stage and severity of disease, and to compare predictions made by influential mathematical models with findings of empirical studies. DESIGN: Linked data analysis combining empirical evidence of the accuracy of the Innova LFT, the probability of positive viral culture or transmission to secondary cases, and the distribution of viral loads of SARS-CoV-2 in individuals in different settings. SETTING: Testing of individuals with symptoms attending NHS Test-and-Trace centres across the UK, residents without symptoms attending municipal mass testing centres in Liverpool, and students without symptoms screened at the University of Birmingham. PARTICIPANTS: Evidence for the sensitivity of the Innova LFT, based on 70 individuals with SARS-CoV-2 and LFT results. Infectiousness was based on viral culture rates on 246 samples (176 people with SARS-CoV-2) and secondary cases among 2 474 066 contacts; distributions of cycle threshold (Ct) values from 231 497 index individuals attending NHS Test-and-Trace centres; 70 people with SARS-CoV-2 detected in Liverpool and 62 people with SARS-CoV-2 in Birmingham (54 imputed). MAIN OUTCOME MEASURES: The predicted proportions who were missed by LFT and viral culture positive and missed by LFT and sources of secondary cases, in each of the three settings. Predictions were compared with those made by mathematical models. RESULTS: The analysis predicted that of those with a viral culture positive result, Innova would miss 20% attending an NHS Test-and-Trace centre, 29% without symptoms attending municipal mass testing, and 81% attending university screen testing without symptoms, along with 38%, 47%, and 90% of sources of secondary cases. In comparison, two mathematical models underestimated the numbers of missed infectious individuals (8%, 10%, and 32% in the three settings for one model, whereas the assumptions from the second model made it impossible to miss an infectious individual). Owing to the paucity of usable data, the inputs to the analyses are from limited sources. CONCLUSIONS: The proportion of infectious people with SARS-CoV-2 missed by LFTs is substantial enough to be of clinical importance. The proportion missed varied between settings because of different viral load distributions and is likely to be highest in those without symptoms. Key models have substantially overestimated the sensitivity of LFTs compared with empirical data. An urgent need exists for additional robust well designed and reported empirical studies from intended use settings to inform evidence based policy.

Clinical feasibility of a contactless multiparameter continuous monitoring technology for neonates in a large public maternity hospital in Nairobi, Kenya.

Multiparameter continuous physiological monitoring (MCPM) technologies are critical in the clinical management of high-risk neonates; yet, these technologies are frequently unavailable in many African healthcare facilities. We conducted a prospective clinical feasibility study of EarlySense's novel under-mattress MCPM technology in neonates at Pumwani Maternity Hospital in Nairobi, Kenya. To assess feasibility, we compared the performance of EarlySense's technology to Masimo's Rad-97 pulse CO-oximeter with capnography technology for heart rate (HR) and respiratory rate (RR) measurements using up-time, clinical event detection performance, and accuracy. Between September 15 and December 15, 2020, we collected and analyzed 470 hours of EarlySense data from 109 enrolled neonates. EarlySense's technology's up-time per neonate was 2.9 (range 0.8, 5.3) hours for HR and 2.1 (range 0.9, 4.0) hours for RR. The difference compared to the reference was a median of 0.6 (range 0.1, 3.1) hours for HR and 0.8 (range 0.1, 2.9) hours for RR. EarlySense's technology identified high HR and RR events with high sensitivity (HR 81%; RR 83%) and specificity (HR 99%; RR 83%), but was less sensitive for low HR and RR (HR 0%; RR 14%) although maintained specificity (HR 100%; RR 95%). There was a greater number of false negative and false positive RR events than false negative and false positive HR events. The normalized spread of limits of agreement was 9.6% for HR and 28.6% for RR, which met the a priori-identified limit of 30%. EarlySense's MCPM technology was clinically feasible as demonstrated by high percentage of up-time, strong clinical event detection performance, and agreement of HR and RR measurements compared to the reference technology. Studies in critically ill neonates, assessing barriers and facilitators to adoption, and costing analyses will be key to the technology's development and potential uptake and scale-up.

Laser induced breakdown spectroscopy for the rapid detection of SARS-CoV-2 immune response in plasma.

As the SARS-CoV-2 pandemic persists, methods that can quickly and reliably confirm infection and immune status is extremely urgently and critically needed. In this contribution we show that combining laser induced breakdown spectroscopy (LIBS) with machine learning can distinguish plasma of donors who previously tested positive for SARS-CoV-2 by RT-PCR from those who did not, with up to 95% accuracy. The samples were also analyzed by LIBS-ICP-MS in tandem mode, implicating a depletion of Zn and Ba in samples of SARS-CoV-2 positive subjects that inversely correlate with CN lines in the LIBS spectra.

A Commercial Anti-TIF1γ ELISA Is Superior to Line and Dot Blot and Should Be Considered as Part of Routine Myositis-Specific Antibody Testing.

Objectives: Anti-TIF1γ is an important autoantibody in the diagnosis of cancer-associated dermatomyositis and the most common autoantibody in juvenile onset dermatomyositis. Its reliable detection is important to instigate further investigations into underlying malignancy in adults. We previously showed that commercial assays using line and dot blots do not reliably detect anti-TIF1γ. We aimed to test a new commercial ELISA and compare with previously obtained protein immunoprecipitation. Methods: Radio-labelled immunoprecipitation had previously been used to determine the autoantibody status of patients with immune-mediated inflammatory myopathies and several healthy controls. ELISA was undertaken on healthy control and anti-TIF1γ sera and compared to previous immunoprecipitation data. Results: A total of 110 serum samples were analysed: 42 myositis patients with anti- TIF1γ and 68 autoantibody negative healthy control sera. Anti-TIF1γ was detected by ELISA in 41 out of 42 of the anti-TIF1γ-positive samples by immunoprecipitation, and in none of the healthy controls, giving a sensitivity of 97.6% and specificity of 100%. The false negative rate was 2%. Conclusion: ELISA is an affordable and time-efficient method which is accurate in detecting anti-TIF1γ.

Investigation of discordant SARS-CoV-2 RT-PCR results using minimally processed saliva.

Saliva is an attractive sample for coronavirus disease 2019 testing due its ease of collection and amenability to detect viral RNA with minimal processing. Using a direct-to-RT-PCR method with saliva self-collected from confirmed COVID-19 positive volunteers, we observed 32% false negative results. Confirmed negative and healthy volunteer samples spiked with 106 genome copies/mL of heat-inactivated severe acute respiratory syndrome coronavirus 2 showed false negative results of 10% and 13%, respectively. Additional sample heating or dilution of the false negative samples conferred only modest improvements. These results highlight the potential to significantly underdiagnose COVID-19 infections when testing directly from minimally processed heterogeneous saliva samples.