Volumetric Analysis: Effect on Diagnosis and Management of Indeterminate Solid Pulmonary Nodules in Routine Clinical Practice.

OBJECTIVE: To evaluate the effect of volumetric analysis on the diagnosis and management of indeterminate solid pulmonary nodules in routine clinical practice. METHODS: This was a retrospective study with 107 computed tomography (CT) cases of solid pulmonary nodules (range, 6-15 mm), 57 pathology-proven malignancies (lung cancer, n = 34; metastasis, n = 23), and 50 benign nodules. Nodules were evaluated on a total of 309 CT scans (average number of CTs/nodule, 2.9 [range, 2-7]). CT scans were from multiple institutions with variable technique. Nine radiologists (attendings, n = 3; fellows, n = 3; residents, n = 3) were asked their level of suspicion for malignancy (low/moderate or high) and management recommendation (no follow-up, CT follow-up, or care escalation) for baseline and follow-up studies first without and then with volumetric analysis data. Effect of volumetry on diagnosis and management was assessed by generalized linear and logistic regression models. RESULTS: Volumetric analysis improved sensitivity (P = 0.009) and allowed earlier recognition (P < 0.05) of malignant nodules. Attending radiologists showed higher sensitivity in recognition of malignant nodules (P = 0.03) and recommendation of care escalation (P < 0.001) compared with trainees. Volumetric analysis altered management of high suspicion nodules only in the fellow group (P = 0.008). κ Statistics for suspicion for malignancy and recommended management were fair to substantial (0.38-0.66) and fair to moderate (0.33-0.50). Volumetric analysis improved interobserver variability for identification of nodule malignancy from 0.52 to 0.66 (P = 0.004) only on the second follow-up study. CONCLUSIONS: Volumetric analysis of indeterminate solid pulmonary nodules in routine clinical practice can result in improved sensitivity and earlier identification of malignant nodules. The effect of volumetric analysis on management recommendations is variable and influenced by reader experience.

Thoracic Endovascular Aortic Repair for Chronic Type B Aortic Dissection: Pre- and Postprocedural Imaging.

Aortic dissection is a chronic disease that requires lifelong clinical and imaging surveillance, long after the acute event. Imaging has an important role in prognosis, timing of repair, device sizing, and monitoring for complications, especially in the endovascular therapy era. Important anatomic features at preprocedural imaging include the location of the primary intimal tear and aortic zonal and branch vessel involvement, which influence the treatment strategy. Challenges of repair in the chronic phase include a small true lumen in conjunction with a stiff intimal flap, complex anatomy, and retrograde perfusion from distal reentry tears. The role of thoracic endovascular aortic repair (TEVAR) remains controversial for treatment of chronic aortic dissection. Standard TEVAR is aimed at excluding the primary intimal tear to decrease false lumen perfusion, induce false lumen thrombosis, promote aortic remodeling, and prevent aortic growth. In addition to covering the primary intimal tear with an endograft, several adjunctive techniques have been developed to mitigate retrograde false lumen perfusion. These techniques are broadly categorized into false lumen obliteration and landing zone optimization strategies, such as the provisional extension to induce complete attachment (PETTICOAT), false lumen embolization, cheese-wire fenestration, and knickerbocker techniques. Familiarity with these techniques is important to recognize expected changes and complications at postintervention imaging. The authors detail imaging options, provide examples of simple and complex endovascular repairs of aortic dissections, and highlight complications that can be associated with various techniques. Online supplemental material is available for this article. ©RSNA, 2022.

Rheumatoid arthritis-associated interstitial lung disease: epidemiology, risk/prognostic factors, and treatment landscape.

OBJECTIVES: To summarise the epidemiology, risk and prognostic factors, and treatment landscape of rheumatoid arthritis-associated interstitial lung disease (RA-ILD). METHODS: Targeted and systematic literature reviews were conducted to characterise the epidemiology and treatment landscape associated with RA-ILD, respectively. MEDLINE®, Embase, and CENTRAL were searched via OvidSP in March 2019 and December 2018. The results were narratively summarised. RESULTS: A total of 24 and 20 publications were captured through targeted and systematic literature review, respectively. No randomised controlled trials were identified; publications were observational cohort studies, cross-sectional, or case-control. Unadjusted incidence of interstitial lung disease (ILD) ranged from 1.3/1,000 person-years for interstitial pneumonia-type ILD to 5.0/1,000 person-years for 'probable or definite ILD'. Prevalence of ILD ranged from 1.8% to 67% (median: 24.9%) and varied with case definition and sample size. Few publications identified the same risk and prognostic factors; age, male sex, duration of disease, and antibodies to cyclic citrullinated peptides were the most frequently reported risk factors for development of RA-ILD, and age was the most common predictor of mortality. Despite identification of a variety of pharmacotherapeutic interventions, assessment of the comparative efficacy and safety of the available treatments were difficult due to heterogenous reporting of outcomes and small sample size. CONCLUSIONS: A wide range of estimates were identified for incidence and prevalence of RA-ILD. Further, there was no consensus on risk and prognostic factors. Sufficiently powered clinical trials are needed to confirm the findings of the observational studies with respect to efficacy and safety of current treatments.

Point-of-Care Ultrasound is Associated With Decreased Length of Stay in Children Presenting to the Emergency Department With Soft Tissue Infection.

BACKGROUND: Point-of-care ultrasound (POCUS) is increasingly being used to differentiate cellulitis from abscess in the pediatric emergency department (ED). POCUS has also been shown to decrease length of stay (LOS) for other applications among adult patients. OBJECTIVE: We sought to determine if ED LOS differed for children presenting with skin and soft tissue infections who received POCUS versus radiology-performed ultrasound. METHODS: We performed a retrospective cohort study of children presenting to an urban pediatric ED between January 2011 and June 2013 with a diagnosis of cellulitis or abscess who underwent soft tissue ultrasound. Patients who received a surgical consult, had significant medical comorbidities, or had a lesion located on the face, hands, feet, or groin were excluded. We compared ED LOS among children who received radiology-performed ultrasound to children who received POCUS, adjusting for relevant clinical variables. RESULTS: Among 3094 children with a diagnosis of cellulitis or abscess, we identified 202 who underwent a POCUS and 118 who underwent radiology-performed ultrasound. The POCUS group had a shorter median LOS than the radiology-performed ultrasound group (adjusted median difference -73 min; 95% confidence interval -93.6 to -52.4 min). In the subset of patients discharged from the ED, this difference was more pronounced (adjusted median difference -89 min; 95% confidence interval -109.9 to -68.1 min). CONCLUSION: Among children presenting to a pediatric ED with superficial skin and soft tissue infections, children receiving POCUS experienced shorter LOS compared to children receiving radiology-performed ultrasound.

Bedside Ultrasound for Tracheal Tube Verification in Pediatric Emergency Department and ICU Patients: A Systematic Review.

OBJECTIVES: Improper placement of the tracheal tube during intubation can lead to dangerous complications, and bedside ultrasound has been proposed as a method of quickly and accurately identifying tube placement. Recent studies in adults have found it to be accurate, but its applicability in pediatric patients is unclear. This systematic review aims to describe the current available data on the accuracy and feasibility of bedside ultrasound for tracheal tube placement in children. DATA SOURCES: OVID MEDLINE and EMBASE. STUDY SELECTION: Available articles on bedside neck or lung/diaphragm ultrasound for confirmation of tracheal tube placement in children through December 2015. DATA EXTRACTION: Two reviewers screened studies for eligibility and abstracted data independently. The quality of selected articles was evaluated using Quality Assessment of Diagnostic Accuracy Studies statement. DATA SYNTHESIS: A total of nine articles were identified: one study using neck ultrasound, two using lung/diaphragmatic ultrasound, one with both, and five studies looking at direct visualization of the tracheal tube tip met our inclusion criteria. There were 81 intubations evaluated using neck ultrasound, 214 intubations evaluated using diaphragmatic or pleural sliding, and 165 intubations evaluated for feasibility of bedside ultrasound in visualizing tracheal tube tip placement. The sensitivities of transtracheal ultrasound for intubation were overall high ranging from 0.92 to 1.00 with excellent specificities at 1.00. For lung ultrasound, the sensitivities for tracheal placement versus esophageal placement were high at 1.00, but only one study reported esophageal intubations and had a specificity of 1.00. When assessing the appropriate tracheal tube depth for tracheal intubations using lung ultrasound, the sensitivities ranged from 0.91 to 1.00 with specificities ranging from 0.5 to 1.0. Regarding feasibility of direct visualization of tracheal tube tip, visualization ranged from 83% to 100%. CONCLUSION: Bedside ultrasound has been described to be feasible in determining tracheal tube placement in several small single center studies and could be a useful adjunct tool in confirming tracheal tube placement in critically ill pediatric patients, but further studies are needed to assess its accuracy in a randomized multicenter setting.

Observation vs admission in syncope: can we predict short length of stays?

BACKGROUND: Rising health care costs demands justifying prolonged hospitalization for syncope, yet predictors of shorter length of stay (LOS) have not been identified. OBJECTIVE: The objective of this study is to identify independent predictors of LOS for syncope patients presenting to the emergency department (ED). METHODS: We performed an analysis of a prospectively collected cohort of ED syncope patients. We examined risk factors from the patient's ED presentation and workup and used Spearman rank correlation to evaluate the relationship between these risk factors and LOS in a logistic regression model for prediction of hospitalization less than 1 day. RESULTS: Of 568 total syncope patients, 350 (61.6%) were admitted and comprise the study cohort. Mean age was 57 years (SD, ±25 years); 39.6% were male. Length of hospitalization was less than or equal to 1 in 179 patients (51.1%). The number of risk factors was associated with LOS (P < .001). Most hospitalized patients with less than 1 predictor were hospitalized for less than 1 day (152/272; 55.9%). In multivariate logistic regression analysis, clear vasovagal etiology was positively correlated with LOS less than 1 day (odds ratio [OR], 1.92), whereas dysrhythmia (OR, 0.3), coronary artery disease (OR, 0.33), abnormal vital signs (OR, 0.35), implantable defibrillator/pacemaker (OR, 0.29), anemia/gastrointestinal bleeding (OR, 0.34), and central nervous system abnormalities (OR, 0.09; P < .05 for all) were negatively correlated with LOS less than 1 day. Area under the curve for model accuracy was moderate: 0.70 (95% confidence interval, 0.65-0.76). CONCLUSION: Patients with less than 1 predictor of prolonged stay, who present to the ED with syncope, are unlikely to require hospitalization of more than 1 day. A set of predictors may help define which patients are appropriate for 24-hour observation rather than full hospitalization.

Host cell protein testing by ELISAs and the use of orthogonal methods.

Host cell proteins (HCPs) are among the process-related impurities monitored during recombinant protein pharmaceutical process development. The challenges of HCP detection include (1) low levels of residual HCPs present in large excess of product protein, (2) the assay must measure a large number of different protein analytes, and (3) the population of HCP species may change during process development. Suitable methods for measuring process-related impurities are needed to support process development, process validation, and control system testing. A multi-analyte enzyme-linked immunosorbent assay (ELISA) is the workhorse method for HCP testing due to its high throughput, sensitivity and selectivity. However, as the anti-HCP antibodies, the critical reagents for HCP ELISA, do not comprehensively recognize all the HCP species, it is especially important to ensure that weak and non-immunoreactive HCPs are not overlooked by the ELISA. In some cases limited amount of antibodies to HCP species or antigen excess causes dilution-dependent non-linearity with multi-product HCP ELISA. In our experience, correct interpretation of assay data can lead to isolation and identification of co-purifying HCP with the product in some cases. Moreover, even if the antibodies for a particular HCP are present in the reagent, the corresponding HCP may not be readily detected in the ELISA due to antibody/antigen binding conditions and availability of HCP epitopes. This report reviews the use of the HCP ELISA, discusses its limitations, and demonstrates the importance of orthogonal methods, including mass spectrometry, to complement the platform HCP ELISA for support of process development. In addition, risk and impact assessment for low-level HCPs is also outlined, with consideration of clinical information.

Barriers to Completing Low Dose Computed Tomography Scan for Lung Cancer Screening.

INTRODUCTION: Annual low-dose computed tomography (LDCT) screening has been shown to reduce lung cancer mortality in high-risk individuals by detecting the disease at an earlier stage. This study aims to assess the barriers to completing LDCT in a cohort of patients who were determined eligible for lung cancer screening (LCS). METHODS: We performed a single institution, mixed methods, cross-sectional study of patients who had a LDCT ordered from July to December 2022. We then completed phone surveys with patients who did not complete LDCT to assess knowledge, attitude, and perceptions toward LCS. RESULTS: We identified 380 patients who met inclusion criteria, including 331 (87%) who completed LDCT and 49 (13%) who did not. Patients who completed a LDCT and those who did not were similar regarding age, sex, race, primary language, household income, body mass index, median pack years, and quit time. Positive predictors of LDCT completion were: meeting USPSTF guidelines (97.9% vs 81.6%), being married (58.3% vs 44.9%), former versus current smokers (55% vs 41.7%), personal history of emphysema (60.4% vs 42.9%), and family history of lung cancer (13.9% vs 4.1%) (all P < .05). Of the patients who participated in the phone survey, only 7% of respondents thought they were high risk for developing lung cancer despite attending a shared decision-making visit and only 10% wanted to re-schedule their LDCT. CONCLUSION: There exist barriers to completing LDCT even after patients are identified as eligible and complete a shared decision-making visit secondary to knowledge barriers, misperceptions, and patient disinterest.

'I want him to tell me he loves me': A smart audio device, Tochie, for resident-family connection in long-term care.

BACKGROUND: Older people living in long-term care homes are particularly susceptible to loneliness and social isolation, which the COVID-19 pandemic has exacerbated further. 'Tochie' is a smart audio device that allows family members to remotely record and send messages, such as daily reminders and comforting recordings, to their loved ones in LTC settings. The purpose of this study was to assess the feasibility and acceptability of using Tochie to improve resident-family connections, and to investigate user experience, impact and lessons learned. METHODS: Participants included 10 residents, nine family members and six care staff from two LTC homes in British Columbia, Canada. A Tochie was provided to each resident to use with their family members over a 4-week intervention period. The research team provided support and gathered feedback from family members and care staff through weekly phone and email correspondence. Qualitative descriptive design was used, including pre- and post-intervention focus groups and interviews held via Zoom and phone to gather participants' experiences with Tochie. Themes were identified through thematic analysis. RESULTS: Three themes were identified: (1) Facilitating emotional connection, (2) Using the device in creative and personalised ways and (3) Structural challenges and supports. Based on these findings, recommendations for future research and practice are provided. CONCLUSION: The COVID-19 pandemic has prompted a rethinking of what it means to 'stay in touch' with loved ones in LTC settings. This study found that Tochie has opened up new opportunities for family connection and provided emotional support for residents. The results of this study offer valuable insights into the implementation of assistive technology in LTC homes to support resident care.

Involvement of frontline clinicians in healthcare technology development: Lessons learned from a ventilator project.

Co-development of healthcare technology with users helps produce user-friendly products, ensuring safe device usage and meeting patients' needs. For developers considering healthcare innovations, engaging user experience can reduce production time and cost while maximizing device application. The purpose of this paper is to report lessons learned from the development of a 3D printed origami ventilator prototype in response to the rise of ventilator demand due to the Coronavirus disease (COVID-19) pandemic. We conducted focus groups with frontline clinicians working in an Intensive Care Unit of a large urban hospital in Vancouver, British Columbia, Canada. In the interdisciplinary focus groups, we identified challenges, practical tips about product development, the human needs of technology, and cross-discipline peer learning. The focus group discussions provide useful insight into the technology development for complex clinical contexts. Based on our experiences, we articulate five practical tips for co-development of healthcare technology - AGILE: Analyse users' needs first, Gain insights into complex context, Involve users early and frequently, Lead with a prototype, and Educate and support. Through sharing the tips and lessons learned, we wish to emphasize the necessity of meaningful multi-disciplinary collaboration during healthcare technology development and promote the inclusion of frontline clinicians during these initiatives. Supplementary Information: The online version contains supplementary material available at 10.1007/s12553-022-00655-w.

Reducing Pediatric Emergency Department Prescription Errors.

BACKGROUND: Prescription errors are a significant cause of iatrogenic harm in the health care system. Pediatric emergency department (ED) patients are particularly vulnerable to error. We sought to decrease prescription errors in an academic pediatric ED by 20% over a 24-month period by implementing identified national best practice guidelines. METHODS: From 2017 to 2019, a multidisciplinary, fellow-driven quality improvement (QI) project was conducted using the Model for Improvement. Four key drivers were identified including simplifying the electronic order entry into prescription folders, improving knowledge of dosing by indication, increasing error feedback to prescribers, and creating awareness of common prescription pitfalls. Four interventions were subsequently implemented. Outcome measures included prescription errors per 1000 prescriptions written for all medications and top 10 error-prone antibiotics. Process measures included provider awareness and use of prescription folders; the balancing measure was provider satisfaction. Differences in outcome measures were assessed by statistical process control methodology. Process and balancing measures were analyzed using 1-way analysis of variance and χ2 testing. RESULTS: Before our interventions, 8.6 errors per 1000 prescriptions written were identified, with 62% of errors from the top 10 most error-prone antibiotics. After interventions, error rate per 1000 prescriptions decreased from 8.6 to 4.5 overall and from 20.1 to 8.8 for top 10 error-prone antibiotics. Provider awareness of prescription folders was significantly increased. CONCLUSION: QI efforts to implement previously defined best practices, including simplifying and standardizing computerized provider order entry (CPOE), significantly reduced prescription errors. Synergistic effect of educational and technological efforts likely contributed to the measured improvement.

Diagnosing invasive fungal disease in critically ill patients.

Fungal infections are increasing, with a changing landscape of pathogens and emergence of new groups at risk for invasive disease. We review current diagnostic techniques, focusing on studies in critically ill patients. Microbiological cultures, the current "gold standard", demonstrate poor sensitivity, thus diagnosis of invasive disease in the critically ill is difficult. This diagnostic dilemma results in under- or over-treatment of patients, potentially contributing to poor outcomes and antifungal resistance. While other current diagnostic tests perform moderately well, many lack timeliness, efficacy, and are negatively affected by treatments common to critically ill patients. New nucleic acid-based research is promising.

CT screening and follow-up of lung nodules: effects of tube current-time setting and nodule size and density on detectability and of tube current-time setting on apparent size.

OBJECTIVE: The purpose of the study was to quantify and compare the effect of CT dose and of size and density of nodules on the detectability of lung nodules and to quantify the influence of CT dose on the size of the nodules. MATERIALS AND METHODS: From 50 patients a total of 125 cuboidal regions of interest (3 × 3 × 1.5 cm volumes) showing a single nodule (≤ 8 mm) and 27 normal cuboids were selected. Image sets were reconstructed with the software from raw data simulating different dose levels: 300 (original dose), 220, 180, 140, 100, 80, 60, 50, 40, 30, 20, 10, and 5 reference mAs. A logistic regression model was used to analyze detectability for three blinded readers. Odds ratios were calculated for nodule size smaller than 3 mm versus 3 mm and larger and for nodule attenuation of -300 HU and greater versus less than -300 HU. RESULTS: Tube current-time settings of 10 mAs and greater were not associated with a significant difference in individual reader sensitivity compared with the standard setting of 300 mAs. At 5 mAs only one reader had a significant decrease in sensitivity, from 82% to 77% (p = 0.0035). According to the odds ratios and logistic regression results, the strongest negative effect on sensitivity can be assumed for low nodule density followed by small nodule size and dose level. The mean nodule volume measurement error between 5 and 300 mAs was 2.2% ± 18% (SD) and much lower than the interobserver volume measurement error rate of 38% ± 45%. CONCLUSION: The results show the feasibility of a low-dose CT protocol at 10 mAs for follow-up of lung nodules. Computer-aided volume measurement in follow-up of lung nodules decreases interobserver variability.

Yield of diagnostic procedures for invasive fungal infections in neutropenic febrile patients with chest computed tomography abnormalities.

Haematological patients with neutropenic fever are frequently evaluated with chest computed tomography (CT) to rule out invasive fungal infections (IFI). We retrospectively analysed data from 100 consecutive patients with neutropenic fever and abnormal chest CT from 1998 to 2005 to evaluate their chest CT findings and the yield of diagnostic approaches employed. For their initial CTs, 79% had nodular opacities, with 24.1% associated with the halo sign. Other common CT abnormalities included pleural effusions (48%), ground glass opacities (37%) and consolidation (31%). The CT findings led to a change in antifungal therapy in 54% of the patients. Fifty-six patients received diagnostic procedures, including 46 bronchoscopies, 25 lung biopsies and seven sinus biopsies, with a diagnostic yield for IFI of 12.8%, 35.0% and 83.3%, respectively. In conclusion, chest CT plays an important role in the evaluation of haematological patients with febrile neutropenia and often leads to a change in antimicrobial therapy. Pulmonary nodules are the most common radiological abnormality. Sinus or lung biopsies have a high-diagnostic yield for IFI as compared to bronchoscopy. Patients with IFI may not have sinus/chest symptoms, and thus, clinicians should have a low threshold for performing sinus/chest imaging, and if indicated and safe, a biopsy of the abnormal areas.

The association between dietary intake and cervical intraepithelial neoplasia grade 2 or higher among women in a high-risk rural area of China.

OBJECTIVE: To evaluate the relationship between dietary intake and risk of cervical intraepithelial neoplasia grade 2 or higher (CIN2+) while controlling for human papillomavirus (HPV) infection. METHODS: In 1999 and 2002, 11,031 women aged 35­50, were screened as part of two cross-sectional population-based cervical cancer screening studies in China. Dietary food intake information was collected by a 79-item Food Frequency Questionnaire (FFQ). 748 HPV-positive women (557 normal biopsy; 95 CIN2, 79 CIN3 and 17 cancer) with completed interviews and biopsy results were included in our data analysis. Specific dietary food groups were classified into dark-colored vegetables, light-colored vegetables, onion vegetables, legumes, nuts, eggs, and meat. Unconditional logistic regression was used to evaluate the association between dietary intake and the risk of developing CIN2+. RESULTS: Inverse associations between CIN2+ risk and onion vegetables, legumes, nuts, and meat were observed. Comparison of the lowest and highest tertiles for consumption of onion vegetables, legumes, nuts, and meat yielded adjusted odds ratios (ORs) of 0.589 [95% confidence intervals (CI), 0.387­0.897; P for trend = 0.011], 0.591 (95% CI, 0.392­0.892; P for trend = 0.012), 0.635 (95% CI, 0.426­0.946; P for trend = 0.019), 0.624 (95% CI, 0.406­0.958; P for trend = 0.044), respectively, for CIN2+ risk among 748 HPV-positive women. No associations were found between CIN2+ risk and dark-colored vegetables, light-colored vegetables or eggs. CONCLUSIONS: Dietary intake of onion vegetables, legumes, nuts, and meat is associated with reduced risk of CIN2+. These foods may provide a protective factor against CIN2+.

Performance of high-risk human papillomavirus DNA testing as a primary screen for cervical cancer: a pooled analysis of individual patient data from 17 population-based studies from China.

BACKGROUND: Controversy remains over whether high-risk human papillomavirus (HPV) DNA testing should be used as a primary screen for cervical cancer. The aims of our study were to assess whether HPV DNA testing could be applied to cervical-cancer screening programmes in China, as well as other similar developing countries. METHODS: We did a pooled analysis of population-based cervical cancer screening studies done in mainland China from 1999 to 2008 with concurrent HPV DNA testing (Hybrid Capture 2 assay; Qiagen, Gaithersburg, MD, USA), liquid-based cytology (LBC), and visual inspection with acetic acid (VIA). Eligible women were sexually active, not pregnant, had an intact uterus, and had no history of cervical intraepithelial neoplasia (CIN), cervical cancer, or pelvic irradiation. All women positive for any test were referred for colposcopy and biopsy. Cervical lesions were diagnosed by directed or random biopsy. We assessed the diagnostic accuracy of HPV DNA testing for the detection of CIN grade 3 or greater. FINDINGS: 30,371 women from 17 cross-sectional, population-based studies in various parts of China were screened. 1523 women were subsequently excluded because of inadequate HPV DNA specimens or they did not have a biopsy taken, which included women with atypical squamous cells of undetermined significance; low-grade squamous intraepithelial lesion or worse; positive HPV, negative cytology, and missing or positive colposcopy results; and unsatisfactory cytology results. HPV DNA testing had a higher sensitivity of 97·5% (95% CI 95·7-98·7) for detection of CIN grade 3 or worse, and a lower specificity of 85·1% (82·3-87·9), compared with cytology (sensitivity 87·9% [95% CI 84·7-90·7], specificity 94·7% [93·5-96·0]) and VIA (54·6% [48·0-61·2], 89·9% [86·8-93·0]). Sensitivity did not vary by study or age (<35 years, 35-49 years, ≥50 years); however, specificity did vary with age (p<0·0001) and was highest in women younger than 35 years (89·4%; 95% CI 86·1-91·5). An increase in the positive cutoff point from the manufacturer recommended 1 pg/mL to 2 pg/mL led to a decrease in the overall HPV DNA positivity from 16·3% to 13·9% (p<0·0001), which could result in a decrease in referral rates, although sensitivity was slightly lower (97·5% to 95·2%). An increase in the cutoff point to 10 pg/mL in women younger than 35 years maintained a high sensitivity 97·7% (95% CI 87·7-99·9) and increased specificity to 93·5% (95% CI 91·9-94·6). INTERPRETATION: HPV DNA testing is highly sensitive and moderately specific for CIN grade 3 or worse, with consistent results across study sites and age groups-including women younger than 35 years. A rise in the cutoff point might be beneficial for future screening programmes in China, especially when screening women younger than 35 years.

Freehand MRI-guided preoperative needle localization of breast lesions after MRI-guided vacuum-assisted core needle biopsy without marker placement.

PURPOSE: To evaluate the feasibility of magnetic resonance imaging (MRI)-guided preoperative needle localization (PNL) of breast lesions previously sampled by MRI-guided vacuum-assisted core needle biopsy (VACNB) without marker placement. MATERIALS AND METHODS: We reviewed 15 women with 16 breast lesions undergoing MRI-guided VACNB without marker placement who subsequently underwent MRI-guided PNL, both on an open 0.5T magnet using freehand techniques. Mammograms and specimen radiographs were rated for lesion visibility; MRI images were rated for lesion visibility and hematoma formation. Imaging findings were correlated with pathology. RESULTS: The average prebiopsy lesion size was 16 mm (range 4-50 mm) with 13/16 lesions located in mammographically dense breasts. Eight hematomas formed during VACNB (average size 13 mm, range 8-19 mm). PNL was performed for VACNB pathologies of cancer (5), high-risk lesions (5), or benign but discordant findings (6) at 2-78 days following VACNB. PNL targeted the lesion (2), hematoma (4), or surrounding breast architecture (10). Wire placement was successful in all 16 lesions. Final pathology showed six cancers, five high-risk lesions, and five benign findings. CONCLUSION: MRI-guided PNL is successful in removing lesions that have previously undergone VACNB without marker placement by targeting the residual lesion, hematoma, or surrounding breast architecture, even in mammographically dense breasts.

Imaging the Tear Film: A Comparison Between the Subjective Keeler Tearscope-Plus™ and the Objective Oculus® Keratograph 5M and LipiView® Interferometer.

PURPOSE: To compare non-invasive break-up time (NIBUT) when measured with the Tearscope-Plus™ and the Oculus® Keratograph 5M, and to compare lipid layer thicknesses (LLT) when measured with the Tearscope-Plus™ and the LipiView®. This study also set out to establish the repeatability of these methods. METHODS: The following measurements were taken from both eyes of 24 participants on two occasions: non-invasive keratograph break-up time using the Oculus® (NIKBUT-1 and NIKBUT-average), NIBUT using the Tearscope-Plus™, and LLT using the LipiView® (minimum, maximum, and average) and Tearscope-Plus™. The Tearscope-Plus™ grades were converted to nanometers. RESULTS: There were no significant differences between eyes (Tearscope-Plus™ NIBUT: p = 0.52; NIKBUT-1: p = 0.052; NIKBUT-average: p = 0.73; Tearscope-Plus™ LLT: p = 0.13; LipiView® average, maximum, or minimum: p = 0.68, 0.39 and 0.50, respectively) or days (Tearscope-Plus™ NIBUT: p = 0.32; NIKBUT-1: p = 0.65; NIKBUT-average: p = 0.54; Tearscope-Plus™ LLT: p = 0.26; LipiView® average, maximum, or minimum: p = 0.20, 0.09, and 0.10, respectively). LLT was significantly greater with the Tearscope-Plus™ (80.4 ± 34.0 nm) compared with the LipiView® average (56.3 ± 16.1 nm, p = 0.007), minimum (50.1 ± 15.8 nm, p < 0.001) but not maximum (67.2 ± 19.6 nm, p = 0.55). NIBUT was significantly greater with the Tearscope-Plus™ (15.9 ± 10.7 seconds) compared to the NIKBUT-1 (8.2 ± 3.5 seconds, p = 0.006) but not NIKBUT-average (10.9 ± 3.9 seconds, p = 0.08). CONCLUSIONS: The Tearscope-Plus™ is not interchangeable with either the Oculus® K5M measurement of tear stability (NIKBUT-1) or the LipiView® maximum and minimum lipid thickness.

Characterization of ELISA Antibody-Antigen Interaction using Footprinting-Mass Spectrometry and Negative Staining Transmission Electron Microscopy.

We describe epitope mapping data using multiple covalent labeling footprinting-mass spectrometry (MS) techniques coupled with negative stain transmission electron microscopy (TEM) data to analyze the antibody-antigen interactions in a sandwich enzyme-linked immunosorbant assay (ELISA). Our hydroxyl radical footprinting-MS data using fast photochemical oxidation of proteins (FPOP) indicates suppression of labeling across the antigen upon binding either of the monoclonal antibodies (mAbs) utilized in the ELISA. Combining these data with Western blot analysis enabled the identification of the putative epitopes that appeared to span regions containing N-linked glycans. An additional structural mapping technique, carboxyl group footprinting-mass spectrometry using glycine ethyl ester (GEE) labeling, was used to confirm the epitopes. Deglycosylation of the antigen resulted in loss of potency in the ELISA, supporting the FPOP and GEE labeling data by indicating N-linked glycans are necessary for antigen binding. Finally, mapping of the epitopes onto the antigen crystal structure revealed an approximate 90° relative spatial orientation, optimal for a noncompetitive binding ELISA. TEM data shows both linear and diamond antibody-antigen complexes with a similar binding orientation as predicted from the two footprinting-MS techniques. This study is the first of its kind to utilize multiple bottom-up footprinting-MS techniques and TEM visualization to characterize the monoclonal antibody-antigen binding interactions of critical reagents used in a quality control (QC) lot-release ELISA. Graphical Abstract ᅟ.