False-positive Findings Research Articles

The Neck-Persistency-Net: a three-dimensional, convolution, deep neural network aids in distinguishing vital from non-vital persistent cervical lymph nodes in advanced head and neck squamous cell carcinoma after primary concurrent radiochemotherapy

PurposeTo evaluate the diagnostic performance (DP) of the high-resolution contrast computed tomography (HR-contrast-CT) based Neck-Persistency-Net in distinguishing vital from non-vital persistent cervical lymph nodes (pcLNs) in patients with advanced head and neck squamous cell carcinoma (HNSCC) following primary concurrent chemoradiotherapy (CRT) with [18F]-fluorodeoxyglucose positron emission tomography and high-resolution contrast-enhanced computed tomography ([18F]FDG-PET-CT). Furthermore, the Neck-Persistency-Net’s potential to justify omitting post-CRT neck dissection (ND) without risking treatment delays or preventing unnecessary surgery was explored.MethodsAll HNSCC patients undergoing primary CRT followed by post-CRT-ND for pcLNs recorded in the institutional HNSCC registry were analyzed. The Neck-Persistency-Net DP was explored for three scenarios: balanced performance (BalPerf), optimized sensitivity (OptSens), and optimized specificity (OptSpec). Histopathology of post-CRT-ND served as a reference.ResultsAmong 68 included patients, 11 were female and 32 had vital pcLNs. The Neck-Persistency-Net demonstrated good DP with an area under the curve of 0.82. For BalPerf, both sensitivity and specificity were 78%; for OptSens (90%), specificity was 62%; for OptSpec (95%), sensitivity was 54%. Limiting post-CRT-ND to negative results would have delayed treatment in 27%, 40%, and 7% for BalPerf, OptSens and OptSpec, respectively, versus 23% for [18F]FDG-PET-CT. Conversely, restricting post-CRT-ND to positive results would have prevented unnecessary post-CRT-ND in 78%, 60%, and 95% for BalPerf, OptSens and OptSpec, respectively, versus 55% for [18F]FDG-PET-CT.ConclusionThe DP of the Neck-Persistency-Net was comparable to [18F]-FDG-PET-CT. Depending on the chosen decision boundary, the potential to justify the omission of post-CRT-ND without risking treatment delays in false negative findings or reliably prevent unnecessary surgery in false positive findings outperforms the [18F]-FDG-PET-CT.

ER-Targeted PET for Initial Staging and Suspected Recurrence in ER-Positive Breast Cancer

There are insufficient data comparing 16α-18F-fluoro-17β-estradiol (FES) positron emission tomography (PET) computed tomography (CT) with standard-of-care imaging (SOC) for staging locally advanced breast cancer (LABC) or evaluating suspected recurrence. To determine the detection rate of FES PET/CT and SOC for distant metastases in patients with estrogen receptor (ER)-positive LABC and recurrences in patients with ER-positive BC and suspected recurrence. This diagnostic study was conducted as a single-center phase 2 trial, from January 2021 to September 2023. The study design provided 80% power to find a 20% detection rate difference. Participants included patients with ER-positive LABC (cohort 1) or suspected recurrence (cohort 2). Data were analyzed from September 2023 to February 2024. Participants underwent both SOC imaging and experimental FES PET/CT. When there were suspicious lesions on imaging, 1 was biopsied for histopathological reference standard to confirm presence (true positive) or absence (false positive) of malignant neoplasm. The outcome of interest was the detection rate of FES PET CT vs SOC for distant metastases and recurrences. A total of 124 patients were accrued, with 62 in cohort 1 (median [IQR] age, 52 [32-84] years) and 62 in cohort 2 (median [IQR] age, 66 [30-93] years). In cohort 1, of 14 true-positive findings, SOC imaging detected 12 and FES detected 11 (P > .99). In cohort 2, of 23 true-positive findings, SOC detected 16 and FES detected 18 (P = .77). In 30 patients with lobular histology, of 11 true-positive findings, SOC detected 5 and FES detected 9 (P = .29). There were 6 false-positive findings on SOC and 1 false-positive finding on FES PET/CT (P = .13). In this diagnostic study with pathological findings as the reference standard, no difference was found between FES PET/CT and current SOC imaging for detecting distant metastases in patients with ER-positive LABC or recurrences in patients with ER-positive tumors and suspected recurrence. FES PET/CT could be considered for both clinical indications, which are not part of current Appropriate Use Criteria for FES PET. The findings regarding FES PET/CT in patients with lobular tumors, and for lower false positives than current SOC imaging, warrant further investigation.

Biometric description of 34 589 eyes undergoing cataract surgery: sex differences.

To describe gender differences in the biometric parameters of a large sample of patients with cataract. Cataract surgery has evolved from a vision restoration to a refractive procedure, and population-based studies are vital to optimize normative databases and postsurgical outcomes. Miguel Servet University Hospital, Zaragoza, Spain. Retrospective single-center observational study. The study included 34 589 eyes (20 004 patients with cataract). Biometric data were obtained from IOL Master 700 and Pentacam HR. Linear mixed models were used to account for intereye correlation. HofferQST formula was used to calculate the hypothetical distribution of intraocular lens (IOL) power (arbitrary lens; A = 119.2). Most biometric variables showed significant differences between sexes ( P < .0001), such as 0.53 mm shorter eyes found in females, of which 0.16 mm are explained by shorter aqueous depth. Steeper anterior keratometries (∼0.75 diopter [D]) were found in women, to end up in no difference on anterior astigmatism magnitude, but different orientation ( P < .0001). The distribution of IOL power differed between sexes ( P < .001), with the interquartile range shifting 1 D toward more powerful lenses in women and odds ratio (power >26 D) = 2.26, P < .0001 (Fisher). Large sample size studies provide smaller margin of error, higher power, and controlled risk of reporting false (negative or positive) findings. Highly significant differences between sexes in ocular biometry were found; this supports the idea that including sex as a parameter in IOL calculation should be explored and may improve results. In addition, the distribution of IOL powers was provided, which may be useful for manufacturers and hospital stock planning.

The Use of a Tailored Decision Aid to Improve Understanding of Lung Cancer Screening in People With HIV

People with HIV are at increased risk for lung cancer and multimorbidity, complicating the balance of risks and benefits of lung cancer screening. We previously adapted Decision Precision (screenlc.com) to guide shared decision-making for lung cancer screening in people with HIV. Does an HIV-adapted and personally tailored decision aid improve shared decision-making regarding lung cancer screening in people with HIV as measured by knowledge, decisional conflict, and acceptability? This was a single-arm pilot trial of the decision aid in 40 participants with HIV eligible for lung cancer screening. The decision aid included personalized screening recommendations and HIV-specific, five-year risk estimates of lung cancer and all-cause mortality. Participants reviewed the decision aid at shared decision-making visits and completed pre- and post-visit surveys with measures of knowledge about lung cancer screening, acceptability, and decisional conflict. The 40 enrolled participants were a median 62 years old and 60% were currently smoking with median five-year risks of lung cancer and all-cause mortality of 2.0% (IQR 1.4-3.3%) and 4.1% (IQR 3.3-7.9%). Personalized recommendations included "Encourage Screening" for 53% of participants and "Preference Sensitive" recommendations for the remainder. Participants showed improvement in two validated knowledge measures with relative improvement of 60% (p<0.001) on the LCS-12 and 27% (p<0.001) on the LKS-7, with significant improvement on questions regarding false-positive and false-negative findings, incidental findings, lung cancer-specific mortality benefit, and the possible harms of screening. Participants reported low scores on the decisional conflict scale (median score 0, IQR 0-5) and high acceptability. Ninety percent ultimately underwent screening within one month of the visit. This HIV-adapted and personally tailored decision aid improved participants' knowledge of risks, benefits, and characteristics of screening with low decisional conflict and high acceptability. This decision aid can enable high-quality shared decision-making in this high-risk population.

Effectiveness of electroacupuncture on postoperative ileus prevention after abdominal surgery: A systematic review and trial sequential analysis of randomized controlled trials.

We aimed to verify the effectiveness of electroacupuncture on postoperative ileus prevention after abdominal surgery by meta-analysis and trial sequential analysis (TSA). From inception to May 14, 2024, PubMed, the Cochrane Library, Web of Science, and Embase databases were searched. TSA was used to determine an optimal sample size and control false-positive findings. The primary outcome was the time to first defecation (hours). Fourteen studies were included, with 1105 participants. Meta-analysis and TSA revealed firm evidence for benefits that electroacupuncture shorted the time to first defecation (mean difference [MD] -12.73h, I2=22%, P<0.01), the time to first flatus (MD -7.03h, I2=25%, P<0.01), the time to start of sips of water (MD -12.02h, I2=0%, P<0.01), and the time to start of liquid diet (MD -12.97h, I2=0%, P<0.01) compared with usual care. While compared with sham electroacupuncture, meta-analysis and TSA also confirmed that electroacupuncture shortened the time to first defecation (MD -10.81h, I2=31%, P=0.02) and the time to first flatus (MD -10.81h, I2=0%, P<0.01). However, TSA revealed that firm evidence for benefit or futility was not reached for the length of hospital stay and the rates of postoperative prolonged ileus. Electroacupuncture shortened the duration of postoperative ileus in patients undergoing abdominal surgery, and the adverse events related to electroacupuncture were minor. Further investigation of the effect of electroacupuncture on the risk of prolonged postoperative ileus is warranted in the future.

Vaccine-associated axillary lymphadenopathy with a focus on COVID-19 vaccines.

Axillary lymphadenopathy (LA) after COVID-19 vaccination is now known to be a common side effect. In these cases, malignancy cannot always be excluded on the basis of morphological imaging criteria.Narrative review for decision-making regarding control and follow-up intervals for axillary LA according to currently published research. This article provides a practical overview of the management of vaccine-associated LA using image examples and a flowchart and provides recommendations for follow-up intervals. A particular focus is on patients presenting for diagnostic breast imaging. The diagnostic criteria for pathological lymph nodes (LN) are explained.Axillary LA is a common adverse effect after COVID-19 vaccination (0.3-53%). The average duration of LA is more than 100 days. LA is also known to occur after other vaccinations, such as the seasonal influenza vaccine. Systematic studies on this topic are missing. Other causes of LA after vaccination (infections, autoimmune diseases, malignancies) should be considered for the differential diagnosis. If the LA persists for more than 3 months after COVID-19 vaccination, a primarily sonographic follow-up examination is recommended after another 3 months. A minimally invasive biopsy of the LA is recommended if a clinically suspicious LN persists or progresses. In the case of histologically confirmed breast cancer, a core biopsy without a follow-up interval is recommended regardless of the vaccination, as treatment appropriate to the stage should not be influenced by follow-up intervals. For follow-up after breast cancer, the procedure depends on the duration of the LA and the woman's individual risk of recurrence.Vaccination history should be well documented and taken into account when evaluating suspicious LN. Biopsy of abnormal, persistent, or progressive LNs is recommended. Preoperative staging of breast cancer should not be delayed by follow-up. The risk of false-positive findings is accepted, and the suspicious LNs are histologically examined in a minimally invasive procedure. · The vaccination history must be documented (vaccine, date, place of application).. · If axillary LA persists for more than 3 months after vaccination, a sonographic follow-up examination is recommended after 3 months.. · Enlarged LNs that are persistent, progressive in size, or are suspicious on control sonography should be biopsied.. · Suspicious LNs should be clarified before starting oncological therapy, irrespective of the vaccination status, according to the guidelines and without delaying therapy.. · Wilpert C, Wenkel E, Baltzer PA et al. Vaccine-associated axillary lymphadenopathy with a focus on COVID-19 vaccines. Fortschr Röntgenstr 2024; DOI 10.1055/a-2328-7536.

Performance of Tumor Surveillance for Children With Cancer Predisposition

Pediatric oncology patients are increasingly recognized as having an underlying cancer predisposition syndrome (CPS). Surveillance is often recommended to detect new tumors at their earliest and most curable stages. Data on the effectiveness and outcomes of surveillance for children with CPS are limited. To evaluate the performance of surveillance across a wide spectrum of CPSs. This cohort study reviewed surveillance outcomes for children and young adults from birth to age 23 years with a clinical and/or molecular CPS diagnosis from January 1, 2009, through September 31, 2021. Patients were monitored using standard surveillance regimens for their corresponding CPS at a specialty pediatric oncology center. Patients with hereditary retinoblastoma and bone marrow failure syndromes were excluded. Data were analyzed between August 1, 2021, and December 6, 2023. Cancer predisposition syndrome. Outcomes of surveillance were reviewed to evaluate the incidence, spectrum, and clinical course of newly detected tumors. Surveillance modalities were classified for accuracy and assessed for common strengths and weaknesses. A total of 274 children and young adults (mean age, 8 years [range, birth to 23 years]; 144 female [52.6%]) with 35 different CPSs were included, with a median follow-up of 3 years (range, 1 month to 12 years). During the study period, 35 asymptomatic tumors were detected in 27 patients through surveillance (9.9% of the cohort), while 5 symptomatic tumors were detected in 5 patients (1.8% of the cohort) outside of surveillance, 2 of whom also had tumors detected through surveillance. Ten of the 35 tumors (28.6%) were identified on first surveillance imaging. Malignant solid and brain tumors identified through surveillance were more often localized (20 of 24 [83.3%]) than similar tumors detected before CPS diagnosis (71 of 125 [56.8%]; P < .001). Of the 24 tumors identified through surveillance and surgically resected, 17 (70.8%) had completely negative margins. When analyzed across all imaging modalities, the sensitivity (96.4%), specificity (99.6%), positive predictive value (94.3%), and negative predictive value (99.6%) of surveillance were high, with few false-positive (6 [0.4%]) or false-negative (5 [0.3%]) findings. These findings suggest that standardized surveillance enables early detection of new tumors across a wide spectrum of CPSs, allowing for complete surgical resection and successful treatment in the majority of patients.

Detection of a major Lynch Syndrome-causing MLH1 founder variant in a large-scale genotyped cohort

Some 50% of Finnish Lynch Syndrome (LS) cases are caused by a founder variant in MLH1, in which the entire exon 16 has been lost due to an Alu-mediated recombination event. We piloted detecting the variant in FinnGen, a large genotyped cohort comprising approximately 10% of the current Finnish population, and validated the MLH1 founder variant status of identified individuals residing in the Central Finland Biobank catchment area. A consensus sequence flanking the deletion was identified in whole genome sequences of six LS individuals with the founder variant. Genotype data of 212,196 individuals was queried for regional matches to the consensus sequence. Enrichment of cancer and age at cancer onset was compared between matching and non-matching individuals. Variant status was validated for a subset of the identified individuals using a polymerase chain reaction assay. Allelic matches in a chosen target region was detected in 348 individuals, with 89 having a cancer diagnosis (Bonferroni-adjusted p-value = 1), 20 a familial cancer history (p-adj. < .001), with mean age of onset of cancer being 53.6 years (p-adj. = .002). Eighteen of potential variant carriers had been sampled by the Central Finland Biobank, of which four (22%) were validated as true variant carriers. The workflow we have employed identifies MLH1 exon 16 deletion variant carriers from population-wide SNP genotyping data. An alternative design will be sought to limit false positive findings. Large genotyped cohorts provide a potential resource for identification and prevention of hereditary cancer.

HOMA-IR Index and Pediatric Psoriasis Severity-A Retrospective Observational Study.

Psoriasis is a chronic inflammatory disease with specific cutaneous and nail lesions. Recent data has emphasized its systemic nature, highlighting metabolic conditions found in patients. Insulin resistance was identified in adult psoriasis, sometimes related to psoriasis severity. Data regarding this relationship in children are limited. Consequently, we tested the association between the Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) and Psoriasis Area and Severity Index (PASI) using a retrospective dataset of 43 children with various types of psoriasis. First, we attempted to replicate the relationship between the HOMA-IR and PASI. Second, we explored potential associations between these variables and others in the dataset. The results illustrated no association between HOMA-IR and PASI (p-value = 0.512). The exploratory findings hinted at a connection between nail pitting and insulin resistance (p-value = 0.038), yet Bonferroni adjustments suggested the risk of a false-positive finding. Noteworthy associations were found between the HOMA-IR and body mass index (BMI) (p-value = 0.001), the PASI and quality of life impairment (p-value = 0.005), and psoriasis severity and type (p-value = 0.001). The null hypothesis that insulin resistance in children is not positively associated with psoriasis severity cannot be rejected. Pilot estimates of variables and covariates of interest are provided for further confirmatory studies assessing this hypothesis.

False-positive Findings of Large Vessel Vasculitis on FDG-PET in Patients Treated With Immune Checkpoint Inhibitors.

Fluorine-18 fluorodeoxygluocose positron emission tomography (FDG-PET) is increasingly used in the evaluation of response to immune checkpoint inhibitor (ICI) therapy. Incidental findings of increased vessel wall uptake may prompt the concern for ICI-induced large vessel vasculitis (LVV). Precise radiographic and clinical evaluation is required to determine if this represents true vasculitis, as use of immune suppression and ICI discontinuation can have significant impacts on patient outcomes. We performed a retrospective case analysis of 4 consecutive patients referred to 2 rheumatology clinics treated with ICI with incidental findings of LVV on FDG-PET, reviewing their clinical course and radiographic findings. All 4 cases had FDG-PET scans for routine oncology indications and had no associated clinical features of LVV. One patient was treated with corticosteroids and no patients developed any clinical evidence of vasculitis during a mean follow-up period of 17 months (range: 7-33mo). All FDG-PET images reporting LVV underwent a standardized analysis to identify any technical issues or concerns with interpretation. In review of imaging, 3 of the cases may have been due to delayed tracer to scan interval leading to misinterpretation of vascular uptake as suspected LVV. Recognition of technical pitfalls in FDG-PET interpretation is crucial to inform the need for immunosuppression and the safety of continued ICI therapy.

Abstract PO3-27-03: PROMISE Study: Pre-Operatory MRI is not Effective. A Systematic review of impact of magnetic resonance imaging on surgery-decision and clinical outcomes in women with breast cancer

Abstract Background: The use of magnetic resonance imaging (MRI) in patients with breast cancer before surgery has been a subject of ongoing debate and discussion. The role of MRI as a preoperative tool to guide surgical decision-making remains controversial. Some studies suggest that MRI may improve the detection of additional tumors or assess the extent of disease, while others discuss that it may lead to increased false-positive findings and unnecessary interventions. The potential benefits and potential harms of incorporating MRI into the preoperative assessment of breast cancer patients continue to be topics of research and clinical interest. Clarifying the impact of preoperative MRI on surgical outcomes is crucial to inform evidence-based practices and optimize patient care. Until present, there is no pooled analyses from randomized clinical trials perspective of the clinical impact regarding the routine use of MRI. Objectives: This study aims to conduct metanalysis of randomized controlled trials (RCT) to investigate the association between preoperative MRI and surgical outcomes in women with newly diagnosed invasive breast cancer, providing evidence-based recommendations for clinical practice. Methods: A comprehensive search of electronic databases including PubMed, Medline, Embase, Ovid, Cochrane Library, and Web of Science was conducted by three independent researchers from inception to May 2023. The inclusion and exclusion criteria were based on Cochrane's principles. Relevant data from eligible studies were extracted. A systematic evaluation and meta-analysis were performed using the fixed-effects model to estimate the pooled risk ratio (RR) and 95% CI. Results: Out of 21 studies found, 6 were RCTs and 15 observational comparative studies. The results showed that in RCT preoperative MRI significantly reduce the rate of immediate breast conservative surgery (RR=0.94, 95%CI 0.91~0.96, I2=0%) and increase the mastectomy rate (RR=1.88, 95%CI 1.48~2.38, I2=86%). There wasn’t any change in reoperations rates (RR=0,87, 95%CI 0.71~1.07, I2=72%). Only 1 trial reported data on survival, showing no difference between groups. Conclusion: From RCT standpoint, the evidence suggests that preoperative MRI for newly diagnosed invasive breast cancer may not be beneficial to the patients by increasing rate of mastectomy with no survival benefit and that should be considered when offering as a routine practice to patients with breast cancer before surgery. Forest plot of mastectomy as an outcome Forest plot of re-operation as an outcome Citation Format: Andre Mattar, Andressa Amorim, Evandro Mateus, Fabio Bagnoli, Felipe Zerwes, Francisco Pimentel Cavalcante, Guilherme Novita, Lincon Mori, Marcelo Madeira, Marina Diogenes, Marcelo Antonini, Lucas Okumura. PROMISE Study: Pre-Operatory MRI is not Effective. A Systematic review of impact of magnetic resonance imaging on surgery-decision and clinical outcomes in women with breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-27-03.

A Pilot Study for Drug-Resistant Tuberculosis Disease Patients Suggests that A964G (rs153109)—Interleukin 27 may be Protective

Abstract Context: Variation in the transcription of host genes of inflammatory cytokines may underscore variation in their production. Thus, the host-immune status plays a vital role in determining the fate of the invading bacilli. Materials and Methods: Two hundred consenting volunteers and drug-resistant tuberculosis (DR-TB) patients had their blood samples amplified for the A964G (rs153109) gene. The amplicons were digested using the Xhol enzyme for genotyping purpose. Results: Among the cases: AA (homozygous wild type; n = 33), AG (heterozygous wild type; n = 36), GG (homozygous mutant, n = 10), A (wild allele, n = 102), and T (mutant allele; n = 66); while among the healthy volunteers: AA (homozygous wild type; n = 20), AG (heterozygous wild type; n = 40), GG (homozygous mutant, n = 4) A (wild allele, n = 80), and T (mutant allele; n = 48). The Hardy Weinberg Equilibrium (HWE) assessment of the samples from the control participants was statistically significant (P = 0.015). Nevertheless, the assessment of the association between the genotypes and the phenotypes assessed revealed that the healthy volunteers had more (twice) heterozygous genotype (AG) (crude statistics: P =0.045, OR = 1.99 (1.02–3.90)) when compared to the DR-TB patients. Conclusion: Although the AG genotype of A964G (rs153109)—Interleukin 27 gene may have a protective role against the development of MTB/XPERT positive DR-TB disease, the significant HWE finding among the genotype from the samples of the healthy volunteers suggests that this current result may be a false positive finding.

Pathological Variables and Laboratory Values in Infants with Neonatal Cholestasis Showing Nonexcretion on Tc-99m Mebrofenin Hepatobiliary Scans: A Descriptive Study.

Cholescintigraphy using Tc-99m Mebrofenin is routinely performed as an initial diagnostic test in infants with neonatal cholestasis suspected of having biliary atresia. Demonstration of drainage of bile into the small intestine indicates patency of the biliary tract and thus rules out biliary atresia. Non-excretion of tracer into the small intestine, however, can be caused by obstructive as well as non-obstructive conditions, and it is known that false-positive findings are found with the use of Tc-99m Mebrofenin scintigraphy. In the present study, we retrospectively calculated the proportion of infants eventually diagnosed to have biliary atresia that were initially ruled to have a non-excreting cholescintigraphy pattern in our institution. We have also attempted a systematic description of the cardinal histological characteristics, haematological and hepatic biochemical variables in infants with non-excreting patterns. This retrospective, descriptive study was conducted in Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), Puducherry. We reviewed data from infants who underwent cholescintigraphy with Tc-99m Mebrofenin between January 2016 through June 2022. We included infants in whom the scan was ruled "non-excreting" i.e. those infants in whom biliary atresia could not be ruled out based on the results of the scan. The difference in mean for haematological parameters and ALP were compared between the two groups i.e., biliary atresia versus other than biliary atresia by using Independent student's t-test; the remaining liver biochemical parameters were compared by using Mann-Whitney U Test and a p value < 0.05 was considered to be statistically significant. A non-excretory pattern on cholescintigraphy was found to be due to biliary atresia in 49% of cases (as confirmed by exploratory surgery) and an additional 19.6 % of cases by trucut biopsy (total 68.6%). The difference in the mean serum GGT levels was found to be statistically significant (<0.001). A non-draining pattern on cholescintigraphy is caused by biliary atresia in the greater percentage of cases presenting with cholestasis. The difference in mean GGT levels was found to be statistically significant between biliary atresia and other causes of non-draining patterns on cholescintigraphy.

Multiparametric MRI and 18F-PSMA-1007 PET/CT for the Detection of Clinically Significant Prostate Cancer.

Background Multiparametric MRI (mpMRI) is effective for detecting prostate cancer (PCa); however, there is a high rate of equivocal Prostate Imaging Reporting and Data System (PI-RADS) 3 lesions and false-positive findings. Purpose To investigate whether fluorine 18 (18F) prostate-specific membrane antigen (PSMA) 1007 PET/CT after mpMRI can help detect localized clinically significant PCa (csPCa), particularly for equivocal PI-RADS 3 lesions. Materials and Methods This prospective study included participants with elevated prostate-specific antigen (PSA) levels referred for prostate mpMRI between September 2020 and February 2022. 18F-PSMA-1007 PET/CT was performed within 30 days of mpMRI and before biopsy. PI-RADS category and level of suspicion (LOS) were assessed. PI-RADS 3 or higher lesions at mpMRI and/or LOS 3 or higher lesions at 18F-PSMA-1007 PET/CT underwent targeted biopsies. PI-RADS 2 or lower and LOS 2 or lower lesions were considered nonsuspicious and were monitored during a 1-year follow-up by means of PSA testing. Diagnostic accuracy was assessed, with histologic examination serving as the reference standard. International Society of Urological Pathology (ISUP) grade 2 or higher was considered csPCa. Results Seventy-five participants (median age, 67 years [range, 52-77 years]) were assessed, with PI-RADS 1 or 2, PI-RADS 3, and PI-RADS 4 or 5 groups each including 25 participants. A total of 102 lesions were identified, of which 80 were PI-RADS 3 or higher and/or LOS 3 or higher and therefore underwent targeted biopsy. The per-participant sensitivity for the detection of csPCa was 95% and 91% for mpMRI and 18F-PSMA-1007 PET/CT, respectively, with respective specificities of 45% and 62%. 18F-PSMA-1007 PET/CT was used to correctly differentiate 17 of 26 PI-RADS 3 lesions (65%), with a negative and positive predictive value of 93% and 27%, respectively, for ruling out or detecting csPCa. One additional significant and one insignificant PCa lesion (PI-RADS 1 or 2) were found at 18F-PSMA-1007 PET/CT that otherwise would have remained undetected. Two participants had ISUP 2 tumors without PSMA uptake that were missed at PET/CT. Conclusion 18F-PSMA-1007 PET/CT showed good sensitivity and moderate specificity for the detection of csPCa and ruled this out in 93% of participants with PI-RADS 3 lesions. Clinical trial registration no. NCT04487847 © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Turkbey in this issue.

The Predictive Power of Bosniak 3 and 4 Cystic Renal Lesion Categorization Using Contrast-Enhanced Ultrasound.

Contrast-enhanced ultrasound (CEUS) is increasingly utilized for the noninvasive assessment of renal cystic lesions, using the Bosniak grading system. Bosniak 3-4 lesions require surgical referral, which allows correlation with the histopathological outcome. In this single-center, retrospective study we evaluated renal CEUS exams conducted with SonoVue® with a diagnosis of a Bosniak 3 or 4 lesion between 2019 and 2022. A total of 49 patients and 50 lesions met the inclusion criteria, 31 lesions had available histopathological results. Patient demographics, cyst morphology, and dominant imaging features were registered. The histopathological diagnosis was considered a reference standard. Positive predictive power (PPV) for neoplastic lesions was comparable in the Bosniak 3 and 4 categories (75 vs 93.3%, P = .33), while PPV for histopathologically malignant lesion was considerably higher in the latter group (25 vs 93.33%, P = .0002). None of the lesions which had vividly enhancing thin septa as their dominant CEUS feature were malignant. Oncocytoma, multilocular cystic renal neoplasm of low malignant potential, and cystic nephroma were the major benign entities among Bosniak 3 lesions. Localized cystic kidney disease and hemorrhagic cysts were found to be the primary mimickers leading to false positive imaging findings. CEUS has a high predictive power for malignancy in the Bosniak 4 category, which is not maintained in the Bosniak 3 group due to the large proportion of benign lesions. Adherence to rigorous rule-in criteria and active surveillance strategies need to be considered for equivocal CEUS Bosniak 3 lesions.

Magnetic resonance imaging in the second trimester as a complement to ultrasound for diagnosis of fetal anomalies.

Fetal ultrasound has limitations, especially if the patient is obese or in cases with oligohydramnios. Magnetic resonance imaging (MRI) can then be used as a complement, but only few studies have focused on examinations in the second trimester. To validate MRI as a complement to diagnose fetal anomalies in the second trimester. This retrospective study retrieved data from January 2008 to July 2012 from the Fetal Medicine Unit and Department of Radiology at Uppsala University Hospital. Ultrasound and MRI findings were reviewed in 121 fetuses in relation to the final diagnosis, including postpartum follow-up and autopsy results. Of the 121 fetuses, 51 (42%) had a CNS anomaly and 70 (58%) a non-CNS anomaly diagnosed or suspected. MRI provided additional information in 21% of all cases without changing the management and revealed information that changed the management of the pregnancy in 13%. When a CNS anomaly was detected or suspected, the MRI provided additional information in 22% and changed the management in 10%. The corresponding figures for non-CNS cases were 21% and 16%, respectively. The proportion of cases with additional information that changed the management was especially high in patients with a BMI >30kg/m2 (25%) and in patients with oligohydramnios (38%). In five cases in category III, false-positive ultrasound findings were identified. MRI in the second trimester complements ultrasound and improves diagnosis of fetal CNS- and non-CNS anomalies especially when oligohydramnios or maternal obesity is present.

Cerebrospinal fluid reference proteins increase accuracy and interpretability of biomarkers for brain diseases.

Cerebrospinal fluid (CSF) biomarkers reflect brain pathophysiology and are used extensively in translational research as well as in clinical practice for diagnosis of neurological diseases, e.g., Alzheimer's disease (AD). However, CSF biomarker concentrations may be influenced by non-disease related inter-individual variability. Here we use a data-driven approach to demonstrate the existence of inter-individual variability in mean standardized CSF protein levels. We show that these non-disease related differences cause many commonly reported CSF biomarkers to be highly correlated, thereby producing misleading results if not accounted for. To adjust for this inter-individual variability, we identified and evaluated high-performing reference proteins which improved the diagnostic accuracy of key CSF AD biomarkers. Our reference protein method attenuates the risk for false positive findings, and improves the sensitivity and specificity of CSF biomarkers, with broad implications for both research and clinical practice.

Categorization of continuous covariates and complex regression models—friends or foes in intersectionality research

ObjectivesTo reduce health inequities, it is important to identify intersections in characteristics of individuals subject to privilege or disadvantage. Different proposals for that have recently been published. One approach (1) considers models specified with first- and all second-order effects and another (2) the stratification based on multiple covariates; both categorize continuous covariates. A simulation study was conducted in order to review both methods with regard to identification of intersections showing true differences, rate of false-positive results, and generalizability to independent data compared to an established approach (3) of backward variable elimination according to Bayesian information criterion (BE-BIC) combined with splines. Study Design and SettingR software has been used to simulate the covariates age, sex, body mass index, education, and diabetes to examine their association with a continuous frailty score for osteoporosis using multiple linear regression. In setting 1, none of the covariates was associated with the frailty score, that is, only noise is present in the data. In setting 2, the covariates age, sex, and their interaction were associated with the frailty score, such that only females above 55 years formed an intersection associated with an increased frailty score. All approaches were compared under varying sample sizes (N = 200–3000) and signal-to-noise ratios (SNRs, 0.5–4) in 1000 replications. For model evaluation, bootstrap resampling was used. The models were fitted in internal learning data and then used to predict outcomes in the internal validation data. The mean squared error (MSE) was used for comparison and the frequency of false-positive findings calculated. ResultsIn setting 1, approaches 1 and 2 generated spurious effects in more than 90% of simulations across all sample sizes. In a smaller sample size, approach 3 (BE-BIC) selected 36.5% of the correct model, in larger sample size in 89.8% and always had a lower number of spurious effects. MSE in independent data was generally higher for approaches 1 and 2 when compared to 3. In setting 2, approach 1 selected most frequently the correct interaction but frequently showed spurious effects (>75%). Across all sample sizes and SNR, approach 3 generated least often spurious results and had lowest MSE in independent data. ConclusionCategorization of continuous covariates is detrimental to studies on intersectionality. Due to high and unrestricted model complexity, such approaches are prone to spurious effects and often lack interpretability. Approach 3 (BE-BIC) is considerably more robust against spurious findings, showed better generalizability to independent data, and can be used with most statistical software. For intersectionality research, we consider it most important to describe relevant differences between intersections and to avoid nonreproducible and spurious findings.

Therapeutic mammaplasty does not increase false positive findings on surveillance mammography and ultrasound

Therapeutic mammaplasty does not increase false positive findings on surveillance mammography and ultrasound

False positive findings associated with adenoviral vector-based vaccine underscore the regulatory necessity to eliminate abnormal toxicity test

Accumulating evidence has shown that the abnormal toxicity test (ATT) is not suitable as a quality control batch release test for biologics and vaccines. The purpose of the current study was to explore the optimal ATT experimental design for an adenoviral vector-based vaccine product to avoid false positive results following the standard test conditions stipulated in the Pharmacopoeias. ATT were conducted in both mice and guinea pigs based on methods in Pharmacopeias, with modifications to assess effects of dose volume and amount of virus particles (VPs). The results showed intraperitoneal (IP) dosing at human relevant dose and volume (i.e., VPs), as required by pharmacopeia study design, resulted in false positive findings not associated with extraneous contaminants of a product. Considering many gene therapy products use adeno associated virus as the platform for transgene delivery, data from this study are highly relevant in providing convincing evidence to show the ATT is inappropriate as batch release test for biologics, vaccine and gene therapy products. In conclusion, ATT, which requires unnecessary animal usage and competes for resources which otherwise can be spent on innovative medicine research, should be deleted permanently as batch release test by regulatory authorities around the world.