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Sharon J Parish,1 Rossella E Nappi,2 Michael L Krychman,3 Susan Kellogg-Spadt,4 James A Simon,5 Jeffrey A Goldstein,6 Sheryl A Kingsberg7 1Albert Einstein College of Medicine, Bronx, NY, USA; 2Department of Obstetrics and Gynecology, IRCCS Policlinico San Matteo University, University of Pavia, Pavia, Italy; 3Southern California Center for Sexual Health and Survivorship Medicine and Clinical Faculty University of California Irvine, Newport Beach and Irvine, CA, USA; 4Pelvic and Sexual Health Institute, Philadelphia, PA, USA; 5Obstetrics and Gynecology, George Washington University, Washington, DC, USA; 6Novo Nordisk Inc, Princeton, NJ, USA; 7Departments of Reproductive Biology and Psychiatry, Case Western Reserve University School of Medicine, Cleveland, OH, USA Abstract: Several recent, large-scale studies have provided valuable insights into patient perspectives on postmenopausal vulvovaginal health. Symptoms of vulvovaginal atrophy, which include dryness, irritation, itching, dysuria, and dyspareunia, can adversely affect interpersonal relationships, quality of life, and sexual function. While approximately half of postmenopausal women report these symptoms, far fewer seek treatment, often because they are uninformed about hypoestrogenic postmenopausal vulvovaginal changes and the availability of safe, effective, and well-tolerated treatments, particularly local vaginal estrogen therapy. Because women hesitate to seek help for symptoms, a proactive approach to conversations about vulvovaginal discomfort would improve diagnosis and treatment. Keywords: health care professional, hypoactive sexual desire disorder, local vaginal estrogen therapy, quality of life, urinary tract infection, vulvovaginal atrophy

Abstract Background Past work on asthmatic African American families revealed a strong linkage peak with modest evidence of association on chromosome 11q. Here, we perform tests of association for asthma and a panel of 609 SNPs in African American subjects using a sliding window approach. While efficient in screening a region of dense genotyping, this approach does create some problems: high numbers of tests, assimilating thousands of results, and questions about setting priorities on regions with association signals. Results We present a newly developed tool, Graphical Assessment of Sliding P-values or GrASP, which uses color display to indicate the width of the sliding windows, significance of individual tests, density of SNP coverage and location of known genes that simplifies some of these issues, and use it to identify regions of interest in these data. Conclusion We demonstrate that GrASP makes it easier to visualize, summarize and prioritize regions of interest from sliding window haplotype analysis, based jointly on the p-value from all the tests from these windows and the building of haplotypes of significance in the region. Using this approach, five regions yielded strong evidence for linkage and association with asthma, including the prior peak linkage region.

Demand for gender-affirming facial surgery is growing rapidly. Frontal sinus setback, one of the key procedures used in gender-affirming facial surgery, has a particularly high impact on gender perception. Mixed reality (MR) allows a user to view and virtually overlay three-dimensional imaging on the patient and interact with it in real time. We used the Medivis's SurgicalAR system in conjunction with the Microsoft HoloLens Lucille2 (Microsoft). Computed tomography imaging was uploaded to SurgicalAR, and a three-dimensional (3D) hologram was projected onto the display of the HoloLens. The hologram was registered and matched to the patient, allowing the surgeon to view bony anatomy and underlying structures in real time on the patient. The surgeon was able to outline the patient's frontal sinuses using the hologram as guidance. A 3D printed cutting guide was used for comparison. Negligible difference between the mixed reality-based outline and 3D-printed outline was seen. The process of loading the hologram and marking the frontal sinus outline lasted less than 10 minutes. The workflow and usage described here demonstrate significant promise for the use of mixed reality as imaging and surgical guidance technology in gender-affirming facial surgery., Competing Interests: Dr. Goldstein received funding from the National Institutes of Health under Grant No. R01 DE032366-01. This grant supports research in skull morphology in craniosynostosis, which is separate and not directly related to the current work. The other authors have no financial interest to declare., (Copyright © 2024 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of The American Society of Plastic Surgeons.)

Can large language models, a form of artificial intelligence (AI), generate persuasive propaganda? We conducted a preregistered survey experiment of US respondents to investigate the persuasiveness of news articles written by foreign propagandists compared to content generated by GPT-3 davinci (a large language model). We found that GPT-3 can create highly persuasive text as measured by participants' agreement with propaganda theses. We further investigated whether a person fluent in English could improve propaganda persuasiveness. Editing the prompt fed to GPT-3 and/or curating GPT-3's output made GPT-3 even more persuasive, and, under certain conditions, as persuasive as the original propaganda. Our findings suggest that propagandists could use AI to create convincing content with limited effort., (© The Author(s) 2024. Published by Oxford University Press on behalf of National Academy of Sciences.)

Breast cancer is a heterogeneous disease with variable survival outcomes. Pathologists grade the microscopic appearance of breast tissue using the Nottingham criteria, which are qualitative and do not account for noncancerous elements within the tumor microenvironment. Here we present the Histomic Prognostic Signature (HiPS), a comprehensive, interpretable scoring of the survival risk incurred by breast tumor microenvironment morphology. HiPS uses deep learning to accurately map cellular and tissue structures to measure epithelial, stromal, immune, and spatial interaction features. It was developed using a population-level cohort from the Cancer Prevention Study-II and validated using data from three independent cohorts, including the Prostate, Lung, Colorectal, and Ovarian Cancer trial, Cancer Prevention Study-3, and The Cancer Genome Atlas. HiPS consistently outperformed pathologists in predicting survival outcomes, independent of tumor-node-metastasis stage and pertinent variables. This was largely driven by stromal and immune features. In conclusion, HiPS is a robustly validated biomarker to support pathologists and improve patient prognosis., (© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Context.—: The distinction between well-differentiated epithelial favorable-histology Wilms tumor (EFHWT) and metanephric adenoma (MA) in children has historically been determined by the required absence of both a fibrous pseudocapsule and mitotic activity in MA. More recently these features have been allowed in adult MA. Mutations in exon 15 of the BRAF gene are reported in up to 88% of MAs but have not been reported in EFHWTs., Objective.—: To clarify the pathologic and molecular features used to distinguish between pediatric MA and EFHWT., Design.—: Stage I epithelial tumors classified as EFHWT on central review (36 patients) were identified from the Children's Oncology Group AREN03B2 study. Thirteen tumors had morphologic features overlapping those of MA and 23 lacked such features; 35 of 36 had tissue available for sequencing of BRAF., Results.—: Patients with EFHWTs with MA features (13) were older (mean, 8.4 versus 1.9 years; P < .001), had smaller tumor diameters (mean, 6.0 versus 9.7 cm; P < .001), and had fewer mitoses (mean, 1 versus 48 mitoses per 10 high-power fields; P < .001) than patients with EFHWT lacking MA features (23). All EFHWTs with MA features contained at least a partial fibrous pseudocapsule; 7 of 12 (58%) had BRAF exon 15 mutation. No BRAF exon 15 mutations were identified in 23 EFHWTs lacking MA features. None of the 13 EFHWT patients with MA features have experienced relapse (median follow-up 5.9 years)., Conclusions.—: Pediatric epithelial neoplasms with features of MA that show partial encapsulation and/or modest mitotic activity may be classified as MAs. Although BRAF mutation supports the diagnosis of MA, it is not required for the diagnosis., Competing Interests: The authors have no relevant financial interest in the products or companies described in this article., (© 2023 College of American Pathologists.)

Motivation: Phecodes are widely used and easily adapted phenotypes based on International Classification of Diseases codes. The current version of phecodes (v1.2) was designed primarily to study common/complex diseases diagnosed in adults; however, there are numerous limitations in the codes and their structure., Results: Here, we present phecodeX, an expanded version of phecodes with a revised structure and 1,761 new codes. PhecodeX adds granularity to phenotypes in key disease domains that are under-represented in the current phecode structure-including infectious disease, pregnancy, congenital anomalies, and neonatology-and is a more robust representation of the medical phenome for global use in discovery research., Availability and Implementation: phecodeX is available at https://github.com/PheWAS/phecodeX., (© The Author(s) 2023. Published by Oxford University Press.)

Background: This study of radiation exposure (RE) to physicians performing structural heart procedures evaluated the efficacy of a novel comprehensive radiation shield compared to those of traditional shielding methods. A novel comprehensive shielding system (Protego, Image Diagnostics Inc) has been documented to provide superior RE protection during coronary procedures compared to that provided by a standard "drop down" shield. The purpose of this study was to assess the efficacy of this shield in transcatheter aortic valve replacement (TAVR) procedures, which are associated with disproportionate RE to operators., Methods: This single-center, 2-group cohort, observational analysis compared RE to the primary physician operator performing TAVR using the Protego shield (n = 25) with that using a standard drop-down shield with personal leaded apparel (n = 25). RE was measured at both thyroid and waist levels with a real-time dosimetry system (RaySafe i3, RaySafe) and was calculated on a mean per case basis. Data were collected on additional procedural parameters, including access site(s) for device implantation, per case fluoroscopy time, air kerma, and patient factors, including body mass index. Between-group comparisons were conducted to evaluate RE by group and measurement sites., Results: The Protego system reduced operator RE by 99% compared to that using standard protection. RE was significantly lower at both the thyroid level (0.08 ± 0.27 vs 79.2 ± 62.4 μSv; P < .001) and the waist level (0.70 ± 1.50 vs 162.0 ± 91.0 μSv, P < .001). "Zero" total RE was documented by RaySafe in 60% (n = 15) of TAVR cases using Protego. In contrast, standard protection did not achieve zero exposure in a single case., Conclusions: The Protego shield system provides superior operator RE protection during TAVR procedures. This shield allows operators to work without the need for personal lead aprons and has potential to reduce catheterization laboratory occupational health hazards., (© 2023 The Author(s).)

Background: The field of plastic surgery has experienced difficulty increasing diversity among trainees, despite significant efforts. Barriers to recruitment of underrepresented in medicine (URM) students are poorly understood. This study assesses URM students' exposure to plastic surgery, access to mentors and research opportunities, and the importance of diversity in the field., Methods: A survey was designed and distributed to members of the Student National Medical Association over 3 months. Survey data were collected using Qualtrics and descriptive statistics, and logistical regressions were performed using SAS., Results: Of the 136 respondents, 75.0% identified as Black (n = 102/136), and 57.4% (n = 66/115) reported a plastic surgery program at their home institution. Of the total respondents, 97.7% (n = 127/130) were concerned about racial representation in plastic surgery, and 44.9% (n = 53/114) would be more likely to apply if there were better URM representation. Most respondents disagreed that there was local (73.4%, n = 58/79) or national (79.2%, n = 57/72) interest in URM recruitment. Students whose plastic surgery programs had outreach initiatives were more likely to have attending (OR 11.7, P < 0.05) or resident mentors (OR 3.0 P < 0.05) and access to research opportunities (OR 4.3, P < 0.05)., Conclusions: URM students feel there is an evident lack of interest in recruiting URM applicants in plastic surgery. Programs with outreach initiatives are more likely to provide URM students access to mentorship and research opportunities, allowing students to make informed decisions about pursuing plastic surgery., Competing Interests: The authors have no financial interest to declare in relation to the content of this article. Disclosure statements are at the end of this article, following the correspondence information., (Copyright © 2023 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of The American Society of Plastic Surgeons.)

Objective: To explore how placental pathology is currently used by clinicians and what placental information would be most useful in the immediate hours after delivery., Study Design: We used a qualitative study design to conduct in-depth, semi-structured interviews with obstetric and neonatal clinicians who provide delivery or postpartum care at an academic medical center in the US (n = 19). Interviews were transcribed and analyzed using descriptive content analysis., Results: Clinicians valued placental pathology information yet cited multiple barriers that prevent the consistent use of pathology. Four main themes were identified. First, the placenta is sent to pathology for consistent reasons, however, the pathology report is accessed by clinicians inconsistently due to key barriers: difficult to find in the electronic medical record, understand, and get quickly. Second, clinicians value placental pathology for explanatory capability as well as for contributions to current and future care, particularly when there is fetal growth restriction, stillbirth, or antibiotic use. Third, a rapid placental exam (specifically including placental weight, infection, infarction, and overall assessment) would be helpful in providing clinical care. Fourth, placental pathology reports that connect clinically relevant findings (similar to radiology) and that are written with plain, standardized language and that non-pathologists can more readily understand are preferred., Conclusion: Placental pathology is important to clinicians that care for mothers and newborns (particularly those that are critically ill) after birth, yet many problems stand in the way of its usefulness. Hospital administrators, perinatal pathologists, and clinicians should work together to improve access to and contents of reports. Support for new methods to provide quick placenta information is warranted., Competing Interests: The details for competing interests for each author are as follows: KG: Co-I R01 (R01EB030130) Development of Software to Rapidly Assess Placenta Images at Birth. Patent application: Systems and Methods Incorporating One or More Modalities to Automatic Placental Analysis. PSU Ref 2022-5452. JA: The author has declared that no competing interests exist. CO-M: The author has declared that no competing interests exist. JP: Reports funding from Pfizer for an RSV vaccine study. WC: Funded by Penn State College of Medicine for research in fetal growth restriction and placental pathology. This work had no bearing on study design, collection, analysis, interpretation of data, and/or decision to submit current work for publication. JG: MPI R01 (R01EB030130) Development of Software to Rapidly Assess Placenta Images at Birth, K08EB030120, Walder Foundation Fund to Retain Clinician Scientists (unnumbered). Patent: Systems and Methods Utilizing Artificial Intelligence for Placental Assessment and Examination. Reference 2019-4905. Patent Application: Systems and Methods Incorporating One or More Modalities to Automatic Placental Analysis. PSU Ref 2022-5452. HS: The author has declared that no competing interests exist. AG: MPI R01 (R01EB030130) Development of Software to Rapidly Assess Placenta Images at Birth. Patent: Systems and Methods Utilizing Artificial Intelligence for Placental Assessment and Examination. Reference 2019-4905. Patent Application: Systems and Methods Incorporating One or More Modalities to Automatic Placental Analysis. PSU Ref 2022-5452., (Copyright: © 2023 Gallagher et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: In utero exposure to human immunodeficiency virus (HIV) and antiretroviral (ART) is associated with adverse birth outcomes, which are often attributed to alterations in placental morphology. This study used structural equation models (SEMs) to examine the impact of HIV and ART exposure on fetal growth outcomes and whether these associations are mediated by placental morphology in urban-dwelling Black South African women., Methods: This prospective cohort study included pregnant women living with HIV (WLWH, n = 122) and not living with HIV (WNLWH, n = 250) that underwent repeated ultrasonography during pregnancy, and at delivery, to determine fetal growth parameters in Soweto, South Africa. The size and the velocity of fetal growth measures (i.e., head and abdominal circumference, biparietal diameter, and femur length) were calculated using the Superimposition by Translation and Rotation. Placenta digital photographs taken at delivery were used to estimate morphometric parameters and trimmed placental weight was measured. All WLWH were receiving ART for the prevention of vertical transmission of HIV., Results: A trend towards a lower placental weight and significantly shorter umbilical cord length was reported in WLWH compared to their counterparts. After sex stratification, umbilical cord length was significantly shorter in males born to WLWH than in male fetuses born to WNLWH (27.3 (21.6-32.8) vs. 31.4 (25.0-37.0) cm, p = 0.015). In contrast, female fetuses born to WLWH had lower placental weight, birth weight (2.9 (2.3-3.1) vs. 3.0 (2.7-3.2) kg), and head circumference (33 (32-34) vs. 34 (33-35) cm) than their counterparts (all p ≤ 0.05). The SEM models showed an inverse association between HIV and head circumference size and velocity in female fetuses. In contrast, HIV and ART exposure was positively associated with femur length growth (both size and velocity) and abdominal circumference velocity in male fetuses. None of these associations appeared to be mediated via placental morphology., Conclusion: Our findings suggest that HIV and ART exposure directly affects head circumference growth in females and abdominal circumference velocity in male fetuses; but may improve femur length growth in male fetuses only., (© 2023. The Author(s).)

Context.—: Myriad forces are changing teaching and learning strategies throughout all stages and types of pathology education. Pathology educators and learners face the challenge of adapting to and adopting new methods and tools. The digital pathology transformation and the associated educational ecosystem are major factors in this setting of change., Objective.—: To identify and collect resources, tools, and examples of educational innovations involving digital pathology that are valuable to pathology learners and teachers at each phase of professional development., Data Sources.—: Sources were a literature review and the personal experience of authors and educators., Conclusions.—: High-quality digital pathology tools and resources have permeated all the major niches within anatomic pathology and are increasingly well applied to clinical pathology for learners at all levels. Coupled with other virtual tools, the training landscape in pathology is highly enriched and much more accessible than in the past. Digital pathology is well suited to the demands of peer-to-peer education, such as in the introduction of new testing, grading, or other standardized practices. We found that digital pathology was well adapted to apply our current understanding of optimal teaching strategies and was effective at the undergraduate, graduate, postgraduate, and peer-to-peer levels. We curated and tabulated many existing resources within some segments of pathology. We identified several best practices for each training or educational stage based on current materials and proposed high-priority areas for potential future development., (© 2023 College of American Pathologists.)

Background: The catheterization laboratory predisposes to occupational health hazards. Chronic radiation exposure (RE) direct injuries include a predilection to cataracts and concerns for cancers. Indirectly adverse effects underly the prevalence of orthopedic maladies in interventionists, linked to the burden of mandatory protective lead aprons. A novel comprehensive shielding system (Protego, Image Diagnostics Inc) has been validated in early studies to provide excellent radiation protection. The system is designed to reduce operator RE sufficient to eliminate the need for personal lead aprons. Recent system refinements offer potentially even greater degrees of protection. This clinical study evaluated the efficacy of this system., Methods: This single-center 2-group cohort study compared physician operator RE utilizing the latest iteration of the Protego shield (n = 25 cases) or standard protection (personal leaded apparel and drop-down shield, n = 25 cases) during routine cardiac catheterization procedures. RE at both thyroid and waist levels were measured with a real-time dosimetry system (Raysafe) and calculated on a mean per case basis at both thyroid and waist levels. Additional parameters collected included procedure type, access site, per case fluoroscopy time, and patient factors including body mass index. Between-group comparisons were conducted to evaluate RE by group and measurement sites., Results: Protection with Protego was superior to standard methods. Protego showed markedly lower RE at both the thyroid level (0.36 ± 0.86 vs 58.5 ± 50.2 μSv; P < .001) and the waist level (0.84 ± 2.99 vs 121.4 ± 171.2 μSv; P < .001. "Zero" total RE was documented in 68% (n = 17) of Protego cases; in contrast, standard protection did not achieve "zero" exposure in a single case., Conclusions: The Protego shield system provides excellent RE protection to the physician operator, achieving "zero" RE in two-thirds of cases. RE was superior to standard protection methods. The magnitude of protection achieves state regulatory standards sufficient to allow operators to perform procedures without orthopedically burdensome lead aprons. This shield system has the potential to reduce occupational health hazards., (© 2023 The Authors.)

Background: We aimed to examine maternal metabolic correlates of neonate body composition, and the potential mediating effect of the placenta., Methods: Data were collected throughout pregnancy and at delivery. An oral glucose tolerance test (OGTT) was conducted in order to diagnose or rule out gestational diabetes mellitus (GDM). Maternal weight and blood pressure were taken and hypertension and gestational weight gain (GWG) were defined. Gestational age, birth weight (BW) and weight to length ration (WLR) were recorded. Photographs were taken of the placenta, and the widths and lengths were measured digitally. Body composition was analysed via air displacement plethysmography or dual-energy x-ray absorptiometry. Mediation models were conducted to determine the mediation effect of the placental variables on the relationships between maternal health variables and neonate outcomes. Next, interaction terms were added to models to determine how maternal and placental variables interacted in their effect on neonate outcomes., Results: A total of n = 280 women were included in the analysis. Majority were overweight or obese. Fourteen percent of women developed GDM during pregnancy, 5% had hypertension during pregnancy, 32% were HIV positive, and 32% had anemia. For the birth weight outcome, coefficients of BMI were attenuated by the addition of placental variables (Model 1 β =18.66 vs Model 2 β =16.40). Similar patterns were evident for GWG and hypertension, and for the WLR outcome. In all cases the addition of the placental variables attenuated associations between maternal exposures and neonatal outcomes, yet the level of significance did not change. Inclusion of interaction terms reversed the direction of the relationships between hypertension and BW and WLR, and between GWG and WLR., Conclusion: The placenta buffers some harmful effects of obesity, GWG, and hypertension on neonate size, and placental efficiency interacted with most maternal risk factors to either counteract, or attenuate relationships with neonate size at birth. However the placenta was unable to completely counteract the negative effect of excess nutrient supply on in utero growth., Competing Interests: Declaration of Competing Interest I declare that I participated in the conception of manuscript, analysis of data, and drafting of the manuscript and that I have seen and approved the final version. I have the following conflicts of interests: None

Background: The pathogenesis of bronchopulmonary dysplasia (BPD) is multifactorial, and there are limited data about prenatal exposures and risk of BPD., Study Design: Our study performed parallel analyses using a logistic regression model in a cohort of 4527 infants with data from a curated registry and using a phenome wide association study (PheWAS) based on ICD9/10-based phecodes. We examined 20 prenatal exposures from a neonatal intensive care unit (NICU) curated registry database related to pregnancy and maternal health as well as 94 maternal diagnosis phecodes with a PheWAS analysis., Result: In both the curated registry and PheWAS analyses, polyhydramnios was associated with an increased risk of BPD (OR 5.70, 95% CI 2.78-11.44, p = 1.37 × 10 -6 )., Conclusion: Our data suggest that polyhydramnios may be a clinical indicator of premature infants at increased risk for bronchopulmonary dysplasia. Combining curated registry data with PheWAS analysis creates a valuable tool to generate hypotheses., Impact: Polyhydramnios was significantly associated with bronchopulmonary dysplasia in both a curated registry and by ICD coding analysis with a phenome wide association study (PheWAS). Preterm polyhydramnios may be a clinical indicator of infants at increased risk for developing bronchopulmonary dysplasia after preterm birth. Combining curated registry with PheWAS analysis creates a valuable tool to generate hypotheses about perinatal risk factors and morbidities associated with preterm birth., (© 2022. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)

Background: Systematic exclusion of pregnant people from interventional clinical trials has created a public health emergency for millions of patients through a dearth of robust safety data for common drugs., Methods: We harnessed an enterprise collection of 2.8 M electronic health records (EHRs) from routine care, leveraging data linkages between mothers and their babies to detect drug safety signals in this population at full scale. Our mixed-methods signal detection approach stimulates new hypotheses for post-marketing surveillance agnostically of both drugs and diseases-by identifying 1,054 drugs historically prescribed to pregnant patients; developing a quantitative, medication history-wide association study; and integrating a qualitative evidence synthesis platform using expert clinician review for integration of biomedical specificity-to test the effects of maternal exposure to diverse drugs on the incidence of neurodevelopmental defects in their children., Results: We replicated known teratogenic risks and existing knowledge on drug structure-related teratogenicity; we also highlight 5 common drug classes for which we believe this work warrants updated assessment of their safety., Conclusion: Here, we present roots of an agile framework to guide enhanced medication regulations, as well as the ontological and analytical limitations that currently restrict the integration of real-world data into drug safety management during pregnancy. This research is not a replacement for inclusion of pregnant people in prospective clinical studies, but it presents a tractable team science approach to evaluating the utility of EHRs for new regulatory review programs-towards improving the delicate equipoise of accuracy and ethics in assessing drug safety in pregnancy., Competing Interests: Competing interestsThe authors declare no competing interests., (© The Author(s) 2022.)

Objective  The endoscopic endonasal approach (EEA) is commonly employed in skull base surgery for neoplasm resection. While nasal deformity following EEA is described, this study aimed to perform a detailed qualitative and quantitative assessment of the associated saddle nose deformity (SND) in particular. Setting/Participants  This is a retrospective review of 20 adult patients with SND after EEA for resection of skull base tumors over a 5-year period at the University of Pittsburgh Medical Center. Main Outcome Measures  Fifteen measurements related to SND were obtained on pre- and postoperative imaging. Statistical analyses were performed to evaluate differences between pre- and postoperative anatomies. Results  The most common EEA was transsellar. Reconstruction techniques included nine free mucosal grafts alone, eight vascularized nasoseptal flaps (NSFs), one combined free mucosal graft/abdominal fat graft, and one combined NSF/fascia lata graft. Imaging analysis showed a trend toward loss of mean nasal height, nasal tip projection, and nasolabial angle postoperatively. Subgroup analysis showed that patients with NSF reconstruction had a significantly decreased nasal tip projection (1.2 mm, p  = 0.039) and increased alar base width (1.2 mm, p  = 0.046) postoperatively. Patients without functional pituitary microadenomas demonstrated significantly increased nasofrontal angle and decreased nasal tip projection on postoperative imaging, in contrast to those with functional adenomas who had no measurable significant changes. Conclusion  Clinically evident SND does not always lead to significant radiographic changes. This analysis suggests that patients who undergo surgery for indications other than functional pituitary microadenomas or who receive NSF reconstruction develop more marked SND on standard imaging tests., Competing Interests: Conflict of Interest None declared., (Thieme. All rights reserved.)

Objective: Adipose tissue is a central regulator of metabolic health and a contributor to systemic inflammation. Patterns of adiposity deposition are important to understand for optimizing health. This study aimed to asses relationships between adiposity deposition and metabolic and inflammatory biomarkers in South African women prior to conception., Methods: Non-pregnant, healthy women ( n  = 298) were recruited for this cross-sectional study via home visits. Body composition was measured by Dual X-ray Absorptiometry. Inflammation markers C-reactive protein (CRP), alpha1-acid glycoprotein (AGP), hemoglobin A1c (HbA1c), and blood pressure were scored according to risk. A summative metabolic health risk score was created for women with obesity. Generalized regression models assessed relationships between adiposity deposition and outcomes with adjustment for potential confounders., Results: Obesity was present in 22% of women (mean age = 20.93 years). Fat mass index was associated with inflammation and metabolic health risk ( β  = 0.58; p  < 0.01). Visceral fat, trunk:limb ratio, android:gynoid ratio, body mass index, weight, and waist circumference were positively associated with CRP, AGP, and metabolic health risk ( p  < 0.01). Weight was associated with Hba1c ( β  < 0.01; p  < 0.05). Participants with obesity and low metabolic health risk had lower fat mass index and visceral fat than participants with obesity and higher metabolic health risk., Conclusions: Black South African women accumulated excess adipose tissue in abdominal regions. While fat mass and body mass were associated with inflammation and metabolic health risk, women with obesity and with lower fat mass index and lower visceral adipose tissue were metabolically protected. Identification of women at risk for metabolic disease preconception could help ensure future healthy pregnancies and prevent transference of risk to offspring., Competing Interests: The authors declare no conflicts of interest., (© 2021 The Authors. Obesity Science & Practice published by World Obesity and The Obesity Society and John Wiley & Sons Ltd.)

The placenta is the first organ to form and performs the functions of the lung, gut, kidney, and endocrine systems. Abnormalities in the placenta cause or reflect most abnormalities in gestation and can have life-long consequences for the mother and infant. Placental villi undergo a complex but reproducible sequence of maturation across the third-trimester. Abnormalities of villous maturation are a feature of gestational diabetes and preeclampsia, among others, but there is significant interobserver variability in their diagnosis. Machine learning has emerged as a powerful tool for research in pathology. To capture the volume of data and manage heterogeneity within the placenta, we developed GestaltNet, which emulates human attention to high-yield areas and aggregation across regions. We used this network to estimate the gestational age (GA) of scanned placental slides and compared it to a baseline model lacking the attention and aggregation functions. In the test set, GestaltNet showed a higher r 2 (0.9444 vs. 0.9220) than the baseline model. The mean absolute error (MAE) between the estimated and actual GA was also better in the GestaltNet (1.0847 weeks vs. 1.4505 weeks). On whole-slide images, we found the attention sub-network discriminates areas of terminal villi from other placental structures. Using this behavior, we estimated GA for 36 whole slides not previously seen by the model. In this task, similar to that faced by human pathologists, the model showed an r 2 of 0.8859 with an MAE of 1.3671 weeks. We show that villous maturation is machine-recognizable. Machine-estimated GA could be useful when GA is unknown or to study abnormalities of villous maturation, including those in gestational diabetes or preeclampsia. GestaltNet points toward a future of genuinely whole-slide digital pathology by incorporating human-like behaviors of attention and aggregation.

Study Design: Retrospective clinical review., Objective: To assess the use of intraoperative computed tomography (CT) image-guided navigation (IGN) and robotic assistance in posterior lumbar surgery and their relationship with patient radiation exposure and perioperative outcomes., Methods: Patients ≥18 years old undergoing 1- to 2-level transforaminal lateral interbody fusion in 12-month period were included. Chart review was performed for pre- and intraoperative data on radiation dose and perioperative outcomes. All radiation doses are quantified in milliGrays (mGy). Univariate analysis and multivariate logistic regression analysis were utilized for categorical variables. One-way analysis of variance with post hoc Tukey test was used for continuous variables., Results: A total of 165 patients were assessed: 12 IGN, 62 robotic, 56 open, 35 fluoroscopically guided minimally invasive surgery (MIS). There was a lower proportion of women in open and MIS groups ( P = .010). There were more younger patients in the MIS group ( P < .001). MIS group had the lowest mean posterior levels fused ( P = .015). Total-procedure radiation, total-procedure radiation/level fused, and intraoperative radiation was the lowest in the open group and highest in the MIS group compared with IGN and robotic groups (all P < .001). Higher proportion of robotic and lower proportion of MIS patients had preoperative CT ( P < .001). Estimated blood loss ( P = .002) and hospital length of stay ( P = .039) were lowest in the MIS group. Highest operative time was observed for IGN patients ( P < .001). No differences were observed in body mass index, Charlson Comorbidity Index, and postoperative complications ( P = .313, .051, and .644, respectively)., Conclusion: IGN and robotic assistance in posterior lumbar fusion were associated with higher intraoperative and total-procedure radiation exposure than open cases without IGN/robotics, but significantly less than MIS without IGN/robotics, without differences in perioperative outcomes. Fluoro-MIS procedures reported highest radiation exposure to patient, and of equal concern is that the proportion of total radiation dose also applied to the surgeon and operating room staff in fluoro-MIS group is higher than in IGN/robotics and open groups.

Background: The COVID-19 pandemic had multiple effects on the provision of health care, including the suspension of elective and nonessential surgeries. The objective of this study was to determine the early effect of the COVID-19 pandemic on the surgical care of patients with cleft lip and/or palate at a high-volume cleft center., Methods: A retrospective comparative cohort study of patients with cleft lip and/or palate undergoing lip adhesion, cleft lip and nose repair, and palatoplasty before and during the pandemic was conducted. There were 50 patients in the prepandemic cohort and 53 in the pandemic cohort., Results: Mean age at lip adhesion was 3.1 ± 1.1 months prepandemic (n = 8) and 3.5 ± 2.5 months in the pandemic cohort (n = 8) ( P = 0.75). One lip adhesion was delayed by 1.6 months. Mean age at cleft lip and nose repair was 6.6 ± 1.9 months prepandemic (n = 23) and 8.0 ± 2.1 months in the pandemic cohort (n = 23) ( P = 0.03). Six pandemic cleft lip and nose repairs were delayed; the mean delay was 2.6 ± 1.8 months. The mean age at palatoplasty was 13.9 ± 2.2 months prepandemic (n = 26) and 14.1 ± 2.9 months in the pandemic cohort (n = 26) ( P = 0.79). Seven pandemic palatoplasties were delayed; the mean delay was 3.3 ± 1.4 months., Conclusions: The COVID-19 pandemic caused delays at each stage of repair for cleft lip and/or palate-related procedures; however, only cleft lip and nose repair were significantly affected. This study emphasizes the importance of remaining vigilant regarding the care of this vulnerable population during this challenging time., Competing Interests: Disclosure: All the authors have no financial interest in relation to the content of this article., (Copyright © 2021 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of The American Society of Plastic Surgeons.)

Objective: Sagittal synostosis is the most common form of isolated craniosynostosis. Although some centers have reported extensive experience with this condition, most reports have focused on a single center. In 2017, the Synostosis Research Group (SynRG), a multicenter collaborative network, was formed to study craniosynostosis. Here, the authors report their early experience with treating sagittal synostosis in the network. The goals were to describe practice patterns, identify variations, and generate hypotheses for future research., Methods: All patients with a clinical diagnosis of isolated sagittal synostosis who presented to a SynRG center between March 1, 2017, and October 31, 2019, were included. Follow-up information through October 31, 2020, was included. Data extracted from the prospectively maintained SynRG registry included baseline parameters, surgical adjuncts and techniques, complications prior to discharge, and indications for reoperation. Data analysis was descriptive, using frequencies for categorical variables and means and medians for continuous variables., Results: Two hundred five patients had treatment for sagittal synostosis at 5 different sites. One hundred twenty-six patients were treated with strip craniectomy and 79 patients with total cranial vault remodeling. The most common strip craniectomy was wide craniectomy with parietal wedge osteotomies (44%), and the most common cranial vault remodeling procedure was total vault remodeling without forehead remodeling (63%). Preoperative mean cephalic indices (CIs) were similar between treatment groups: 0.69 for strip craniectomy and 0.68 for cranial vault remodeling. Thirteen percent of patients had other health problems. In the cranial vault cohort, 81% of patients who received tranexamic acid required a transfusion compared with 94% of patients who did not receive tranexamic acid. The rates of complication were low in all treatment groups. Five patients (2%) had an unintended reoperation. The mean change in CI was 0.09 for strip craniectomy and 0.06 for cranial vault remodeling; wide craniectomy resulted in a greater change in CI in the strip craniectomy group., Conclusions: The baseline severity of scaphocephaly was similar across procedures and sites. Treatment methods varied, but cranial vault remodeling and strip craniectomy both resulted in satisfactory postoperative CIs. Use of tranexamic acid may reduce the need for transfusion in cranial vault cases. The wide craniectomy technique for strip craniectomy seemed to be associated with change in CI. Both findings seem amenable to testing in a randomized controlled trial.

Endoscopic suturectomy combined with supplementary techniques such as spring-assisted expansion and cranial molding helmets for the correction of craniosynostosis is growing in popularity due to the reduced scar burdened, decreased morbidity, and reduced overall cost. The authors present their technique for the correction of isolated coronal craniosynostosis. The use of dedicated endoscopic tools and lit endoscopes permits enhanced visualization and technical ability, particularly at the distal portions of the suturectomy, and may reduce operative time and cerebrospinal fluid leak risk. The video can be found here: https://vimeo.com/515401366., Competing Interests: Disclosures The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this publication., (© 2021, The Authors.)

Spectral imagers, the classic example being the color camera, are ubiquitous in everyday life. However, most such imagers rely on filter arrays that absorb light outside each spectral channel, yielding ∼1/N efficiency for an N-channel imager. This is especially undesirable in thermal infrared (IR) wavelengths, where sensor detectivities are low. We propose an efficient and compact thermal infrared spectral imager comprising a metasurface composed of sub-wavelength-spaced, differently-tuned slot antennas coupled to photosensitive elements. Here, we demonstrate this idea using graphene, which features a photoresponse up to thermal IR wavelengths. The combined antenna resonances yield broadband absorption in the graphene exceeding the 1/N efficiency limit. We establish a circuit model for the antennas' optical properties and demonstrate consistency with full-wave simulations. We also theoretically demonstrate ∼58% free space-to-graphene photodetector coupling efficiency, averaged over the 1050 cm -1 to 1700 cm -1 wavenumber range, for a four-spectral-channel gold metasurface with a 0.883 µm by 6.0 µm antenna pitch. This research paves the way towards compact CMOS-integrable thermal IR spectral imagers.

Events in fetal life impact long-term health outcomes. The placenta is the first organ to form and is the site of juxtaposition between the maternal and fetal circulations. Most diseases of pregnancy are caused by, impact, or are reflected in the placenta. The purpose of this review is to describe the main inflammatory processes in the placenta, discuss their immunology, and relate their short- and long-term disease associations. Acute placental inflammation (API), including maternal and fetal inflammatory responses corresponds to the clinical diagnosis of chorioamnionitis and is associated with respiratory and neurodevelopmental diseases. The chronic placental inflammatory pathologies (CPI), include chronic villitis of unknown etiology, chronic deciduitis, chronic chorionitis, eosinophilic T-cell vasculitis, and chronic histiocytic intervillositis. These diseases are less-well studied, but have complex immunology and show mechanistic impacts on the fetal immune system. Overall, much work remains to be done in describing the long-term impacts of placental inflammation on offspring health., (Copyright © 2020 Goldstein, Gallagher, Beck, Kumar and Gernand.)

Phenotypes extracted from Electronic Health Records (EHRs) are increasingly prevalent in genetic studies. EHRs contain hundreds of distinct clinical laboratory test results, providing a trove of health data beyond diagnoses. Such lab data is complex and lacks a ubiquitous coding scheme, making it more challenging than diagnosis data. Here we describe the first large-scale cross-health system genome-wide association study (GWAS) of EHR-based quantitative laboratory-derived phenotypes. We meta-analyzed 70 lab traits matched between the BioVU cohort from the Vanderbilt University Health System and the Michigan Genomics Initiative (MGI) cohort from Michigan Medicine. We show high replication of known association for these traits, validating EHR-based measurements as high-quality phenotypes for genetic analysis. Notably, our analysis provides the first replication for 699 previous GWAS associations across 46 different traits. We discovered 31 novel associations at genome-wide significance for 22 distinct traits, including the first reported associations for two lab-based traits. We replicated 22 of these novel associations in an independent tranche of BioVU samples. The summary statistics for all association tests are freely available to benefit other researchers. Finally, we performed mirrored analyses in BioVU and MGI to assess competing analytic practices for EHR lab traits. We find that using the mean of all available lab measurements provides a robust summary value, but alternate summarizations can improve power in certain circumstances. This study provides a proof-of-principle for cross health system GWAS and is a framework for future studies of quantitative EHR lab traits., Competing Interests: I have read the journal's policy and the authors of this manuscript have the following competing interests: G.R.A. is an employee of Regeneron Pharmaceuticals. He owns stock and stock options for Regeneron Pharmaceuticals. L.A.B and J.C.D receive royalty payments from Nashville Biosciences, a Vanderbilt University Medical Center owned entity.

Post-delivery analysis of the placenta is useful for evaluating health risks of both the mother and baby. In the U.S., however, only about 20% of placentas are assessed by pathology exams, and placental data is often missed in pregnancy research because of the additional time, cost, and expertise needed. A computer-based tool that can be used in any delivery setting at the time of birth to provide an immediate and comprehensive placental assessment would have the potential to not only to improve health care, but also to radically improve medical knowledge. In this paper, we tackle the problem of automatic placental assessment and examination using photos. More concretely, we first address morphological characterization, which includes the tasks of placental image segmentation, umbilical cord insertion point localization, and maternal/fetal side classification. We also tackle clinically meaningful feature analysis of placentas, which comprises detection of retained placenta (i.e., incomplete placenta), umbilical cord knot, meconium, abruption, chorioamnionitis, and hypercoiled cord, and categorization of umbilical cord insertion type. We curated a dataset consisting of approximately 1300 placenta images taken at Northwestern Memorial Hospital, with hand-labeled pixel-level segmentation map, cord insertion point and other information extracted from the associated pathology reports. We developed the AI-based Placental Assessment and Examination system (AI-PLAX), which is a novel two-stage photograph-based pipeline for fully automated analysis. In the first stage, we use three encoder-decoder convolutional neural networks with a shared encoder to address morphological characterization tasks by employing a transfer-learning training strategy. In the second stage, we employ distinct sub-models to solve different feature analysis tasks by using both the photograph and the output of the first stage. We evaluated the effectiveness of our pipeline by using the curated dataset as well as the pathology reports in the medical record. Through extensive experiments, we demonstrate our system is able to produce accurate morphological characterization and very promising performance on aforementioned feature analysis tasks, all of which may possess clinical impact and contribute to future pregnancy research. This work is the first for comprehensive, automated, computer-based placental analysis and will serve as a launchpad for potentially multiple future innovations., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Autopsy studies suggest that implanting stents in lipid-rich plaque (LRP) may be associated with adverse outcomes., Objectives: The purpose of this study was to evaluate the association between LRP detected by near-infrared spectroscopy (NIRS) and clinical outcomes in patients with coronary artery disease treated with contemporary drug-eluting stents., Methods: In this prospective, multicenter registry, NIRS was performed in patients undergoing coronary angiography and possible percutaneous coronary intervention (PCI). Lipid core burden index (LCBI) was calculated as the fraction of pixels with the probability of LRP >0.6 within a region of interest. MaxLCBI 4mm was defined as the maximum LCBI within any 4-mm-long segment. Major adverse cardiac events (MACE) included cardiac death, myocardial infarction, definite or probable stent thrombosis, or unplanned revascularization or rehospitalization for progressive angina or unstable angina. Events were subcategorized as culprit (treated) lesion-related, nonculprit (untreated) lesion-related, or indeterminate., Results: Among 1,999 patients who were enrolled in the COLOR (Chemometric Observations of Lipid Core Plaques of Interest in Native Coronary Arteries Registry), PCI was performed in 1,621 patients and MACE occurred in 18.0% of patients, of which 8.3% were culprit lesion-related, 10.7% were nonculprit lesion-related, and 3.1% were indeterminate during 2-year follow-up. Complications from NIRS imaging occurred in 9 patients (0.45%), which resulted in 1 peri-procedural myocardial infarction and 1 emergent coronary bypass. Pre-PCI NIRS imaging was obtained in 1,189 patients, and the 2-year rate of culprit lesion-related MACE was not significantly associated with maxLCBI 4mm (hazard ratio of maxLCBI 4mm per 100: 1.06; 95% confidence interval: 0.96 to 1.17; p = 0.28) after adjusting clinical and procedural factors., Conclusions: Following PCI with contemporary drug-eluting stents, stent implantation in NIRS-defined LRPs was not associated with increased periprocedural or late adverse outcomes compared with those without significant lipid., (Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objective: The Phenotype Risk Score (PheRS) is a method to detect Mendelian disease patterns using phenotypes from the electronic health record (EHR). We compared the performance of different approaches mapping EHR phenotypes to Mendelian disease features., Materials and Methods: PheRS utilizes Mendelian diseases descriptions annotated with Human Phenotype Ontology (HPO) terms. In previous work, we presented a map linking phecodes (based on International Classification of Diseases [ICD]-Ninth Revision) to HPO terms. For this study, we integrated ICD-Tenth Revision codes and lab data. We also created a new map between HPO terms using customized groupings of ICD codes. We compared the performance with cases and controls for 16 Mendelian diseases using 2.5 million de-identified medical records., Results: PheRS effectively distinguished cases from controls for all 15 positive controls and all approaches tested (P < 4 × 1016). Adding lab data led to a statistically significant improvement for 4 of 14 diseases. The custom ICD groupings improved specificity, leading to an average 8% increase for precision at 100 (-2% to 22%). Eight of 10 adults with cystic fibrosis tested had PheRS in the 95th percentile prio to diagnosis., Discussion: Both phecodes and custom ICD groupings were able to detect differences between affected cases and controls at the population level. The ICD map showed better precision for the highest scoring individuals. Adding lab data improved performance at detecting population-level differences., Conclusions: PheRS is a scalable method to study Mendelian disease at the population level using electronic health record data and can potentially be used to find patients with undiagnosed Mendelian disease., (© The Author(s) 2019. Published by Oxford University Press on behalf of the American Medical Informatics Association. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

This study aimed to evaluate the effect of craniofacial surgical intervention on the visual pathway's function by comparing pre- to post-operative patterned, visually-evoked potentials (pVEP). A retrospective review was conducted on craniosynostosis patients who had pre- and post-craniofacial surgery pVEP testing. The pVEP measured grade in terms of amplitude latency and morphology of the waveforms. The pre- and post-operative results were compared. The study identified 63 patients (mean age at preoperative pVEP of 16.9 months). Preoperatively, 33 patients (52.4%) had abnormal pVEP. Nine patients had evidence of intracranial hypertension, and of those, eight (88.9%) had abnormal pVEP. Within 6 months postoperatively, 24 of 33 patients (72.7%) with abnormal preoperative pVEP developed normal postoperative pVEP, while all 30 patients with normal preoperative VEP maintained their normal results postoperatively. Significant improvements in pVEP latency in patients with broad or delayed latency waveforms was evident for subjects with preoperative grades 2-4 (grade 2, p = 0.015; grade 3, p = 0.029; grade 4; p = 0.007), while significant postoperative increase in amplitude was significant for patients with abnormally low amplitude grade 3 and 5 waveforms (grade 3, p = 0.011; grade 5, p = 0.029). Serial pVEP testing represents a useful tool for the early detection of visual pathway dysfunction and follow up visual pathway function in craniosynostosis. Surgical intervention for craniosynostosis can result in the reversal of preoperative pVEP abnormalities seen in these patients, resulting in the normalization of the pVEP waveform, amplitude and latency, depending on the preoperative pVEP abnormality.

Ultrasound-accelerated thrombolysis (USAT) is advocated in pulmonary embolism (PE) based on the hypothesis that adjunctive ultrasound provides superior clinical efficacy compared to standard catheter-directed thrombolysis (CDT). This retrospective study was designed to compare outcomes between the two modalities. We analyzed patients with computed tomography-diagnosed PE at our institution treated with either USAT or standard CDT. Efficacy parameters assessed included invasive pulmonary artery systolic pressure (PASP; pre- and 24 hours post-treatment), non-invasive right-to-left ventricle (RV/LV) ratio (pre- and post-treatment), and general clinical outcomes (length-of-stay, significant bleeding, and mortality). We analyzed 98 cases (62 USAT and 36 CDT), in whom massive PE was diagnosed in 7%, intermediate/high risk in 81%, and intermediate/low risk in 12%. Overall, 92% had bilateral clot and 40% saddle embolus. At 24 hours, PASP decreased similarly in both groups (CDT Δ14.7 mmHg, USAT Δ10.8 mmHg; p = 0.14). Post-treatment, CDT showed similar improvement in the RV/LV ratio (CDT Δ0.58 vs USAT Δ0.45; p = 0.07), despite the baseline ratio being greater in the CDT group, indicating more severe RV strain (1.56 ± 0.36 vs 1.40 ± 0.29; p = 0.01). Intensive care unit and hospital length-of-stays were similar in both groups. A trend toward lesser significant bleeding rates in the CDT group (8.3% vs 12.9%, p = 0.74) as well as improved survival-to-discharge (97.2% vs 91.9%, p = 0.66) was observed. Compared to USAT, standard CDT achieves similar beneficial effects on hemodynamics, RV/LV ratios, and clinical outcomes. These observations suggest that salutary clinical results may be achieved without the need for very expensive devices.

RASopathy is caused by dysfunction in the MAPK pathway, and include syndromes like Noonan syndrome (NS), NS with multiple lentigines (formerly known as Leopard syndrome), cardiofaciocutaneous (CFC), Legius syndrome, capillary malformation-arteriovenous malformation, neurofibromatosis type 1, and Costello syndrome. When counted together, RASopathies affect 1/1000 live births, and are characterized by cardiovascular manifestations, short stature, developmental delay, renal, urogenital, skin/skeletal abnormalities, and dysmorphic appearance. NS-one of the most common RASopathies-occurs in 1/1000 to 1/2500 live births. On the other hand, the frequency of CFC is unknown, but it is one of the rarest RASopathies, with estimates of only a few hundred cases worldwide. However, its phenotype overlaps with that of NS. In this case series, we describe 5 patients with a clinical and genetic diagnosis of RASopathy-either NS or CFC-all of whom were also diagnosed with isolated sagittal synostosis (ISS). Medical records from ophthalmology, cardiology, plastic surgery, medical genetics, cleft craniofacial, and neurosurgery were used to determine patient history. In our cohort, late presentation of ISS was the predominant form of ISS presentation. We hope this report further characterizes the burgeoning relationship between RASopathy and ISS. Furthermore, these findings support including sagittal synostosis among the presenting features in the clinical phenotype of RASopathies. Ethical approval was obtained from the university's institutional review board., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

The Press Ganey survey is the most widely used instrument for measuring patient satisfaction. Understanding the factors that influence these surveys may permit better use of survey results and may direct interventions to increase patient satisfaction. Press Ganey Clinician and Group Consumer Assessment of Healthcare Providers and Systems surveys administered to ambulatory spine surgery clinic patients within a large tertiary care network from May 2016 to September 2017 were retrospectively reviewed. Mean comparison testing was performed to measure associations between patient demographics and responses to "overall provider rating" and "recommend this provider's office" survey questions. Mean difference to achieve significance was set at α<0.05. A multivariate analysis was performed to determine independent factors. A total of 1400 survey responses from the offices of 11 orthopedic spine surgeons were included. Patients 18 to 34 years old had significantly lower responses to the overall provider rating question than older patients (P<.001), and increasing patient age was correlated with improved ratings. Highest education level was inversely correlated with satisfaction scores, with patients who had attained graduate level education having the lowest satisfaction scores (P=.001). Those with commercial insurance had significantly lower ratings for recommend this provider's office (P=.042) and overall provider rating (P=.022) questions than those with other insurance types. Patients administered the survey on paper had significantly lower ratings than those administered the survey online (P=.006). Provider ratings were significantly higher when the sex and ethnicity of the patient were concordant with the provider (P=.021). This study showed that independent, nonmodifiable factors such as age, education level, and survey mode were significantly associated with the satisfaction of ambulatory spine surgery clinic patients. [Orthopedics. 2019; 42(3):143-148.]., (Copyright 2019, SLACK Incorporated.)

Background: We report the incidence of Chiari malformation I (CMI) in a cohort of 377 patients with isolated sagittal synostosis (ISS), which is to the best of our knowledge the largest such series reported to date., Methods: A retrospective review of patients seen at a single institution from 2007 to 2017 was completed. ISS, Chiari malformations (CMI and CMII) and hydrocephalus were diagnosed by a senior neuroradiologist (G.Z.). Patients who met the inclusion criteria were divided into early (group A) and late (group B) presenting groups, as well as operated (group I) and unoperated (group II) groups. The patients were further subdivided into group AI (early operated), group AII (early unoperated), group BI (late operated), and group BII (late unoperated). Once identified, patient notes were examined for the following data sets: date of birth, age of presentation, age at last follow-up, other systemic conditions as well as molecular testing results. Surgical interventions, ophthalmological, and other relevant data were recorded. Statistical analysis was run in the form of a chi-square test to identify a significant difference between each subgroup. A literature review of the incidence of Chiari malformations in patients with ISS was conducted., Results: Three hundred seventy-seven patients constitute the study's total cohort (272 were males and 105 females). This cohort was divided into patients who underwent surgical repair of ISS (group 1: n = 200), and patients who did not (group 2: n = 177). The entire cohort was also divided into early (group A: n = 161) and late (group B: n = 216) presenting craniosynostosis. In the total cohort, 22/377 (5.8%) patients with CMI were identified. CMI was found in 14/200 (7.0%) patients in group I, and 8/177 (4.5%) patients in group II. CMI was found in 2/161 (1%) patients in group A, and 20/216 (9.2%) patients in group B. The incidence of CMI in group AI (early operated) was 2/151 (1.3%), in group AII (early unoperated) was 0/10, in group BI (late operated) was 11/49 (21%), and in group BII (late unoperated) was 9/167 (5.4%). Chi-square analysis revealed a significant difference between the incidence of CMI in the early-presenting (group A) and late-presenting (group B) groups ( P = 0.001) and between the late-presenting operated (BI) and late-presenting unoperated (BII) groups ( P = 0.001). The incidence of hydrocephalus was 1.6% (6/377) in the total cohort. However, all patients diagnosed with hydrocephalus came from group II (no surgical ISS correction). The incidence of hydrocephalus in group II was 3.3% (6/177). The incidence of hydrocephalus in group BII (late unoperated ISS) was 3.0% (5/167). The incidence of hydrocephalus in group AII (early unoperated ISS) was 9.0% (1/11)., Conclusions: We noted the highest incidence of CMI-21%-in group BI (late-presenting operated). We noted hydrocephalus in group II (nonoperated), with the highest incidence of hydrocephalus found in the group BII (late-presenting unoperated) subgroup. We therefore recommend patients with ISS receive funduscopic examination to screen for raised intracranial pressure (ICP) associated with CMI and hydrocephalus, especially patients with late-presenting ISS.

Introduction: This study assessed the incidence and risk factors for pseudarthrosis among primary spine fusion patients., Methods: Retrospective review of ACS-NSQIP (2005-2013). Differences in comorbidities between spine fusion patients with and without pseudarthrosis (Pseud, N-Pseud) were assessed using chi-squared tests and Independent Samples t -tests. Binary logistic regression assessed patient-related and procedure-related predictors for pseudarthrosis., Results: 52,402 patients (57yrs, 53%F, 0.4% w/pseudarthrosis). Alcohol consumption (OR:2.6[1.2-5.7]) and prior history of surgical revision (OR:1.6[1.4-1.8]) were risk factors for pseudarthrosis operation. Pseud patients at higher risk for deep incisional SSI (at 30-days:OR:6.6[2.0-21.8]). Pseud patients had more perioperative complications (avg:0.24 ± 0.43v0.18 ± 0.39, p =0.026)., Conclusions: Alcoholism and surgical revision are major risk factors for pseudarthrosis in patients undergoing spine fusion.

Background: Patients with cleft lip and/or palate can undergo numerous procedures to improve appearance, speech, dentition and hearing. We developed a cleft-specific patient-reported outcome instrument to facilitate rigorous international measurement and benchmarking., Methods: Data were collected from patients aged 8-29 years with cleft lip and/or palate at 30 hospitals in 12 countries between October 2014 and November 2016. Rasch measurement theory analysis was used to refine the scales and to examine reliability and validity. Normative CLEFT-Q values were computed for age, sex and cleft type., Results: Analysis led to the refinement of an eating and drinking checklist and 12 scales measuring appearance (of the face, nose, nostrils, teeth, lips, jaws and cleft lip scar), health-related quality of life (psychological, social, school, speech distress) and speech function. All scales met the requirements of the Rasch model. Analysis to explore differential item functioning by age, sex and country provided evidence to support the use of a common scoring algorithm for each scale for international use. Lower (worse) scores on CLEFT-Q scales were associated with having a speech problem, being unhappy with facial appearance, and needing future cleft-related treatments, providing evidence of construct validity. Normative values for age, sex and cleft type showed poorer outcomes associated with older age, female sex and having a visible cleft., Interpretation: The CLEFT-Q represents a rigorously developed instrument that can be used internationally to collect and compare evidence-based outcomes data from patients aged 8-29 years of age with cleft lip and/or palate., Competing Interests: Competing interests: Anne Klassen and Karen Wong Riff are co-developers of the CLEFT-Q and, as such, could potentially receive a share of any licence revenues as royalties based on their institutions’ inventor sharing policy if the CLEFT-Q is used in a for profit study., (© 2018 Joule Inc. or its licensors.)

Background: Spine surgery has been transformed significantly by the growth of minimally invasive surgery (MIS) procedures. Easily marketable to patients as less invasive with smaller incisions, MIS is often perceived as superior to traditional open spine surgery. The highest quality evidence comparing MIS with open spine surgery was examined., Methods: A systematic review of randomized controlled trials (RCTs) involving MIS versus open spine surgery was performed using the Entrez gateway of the PubMed database for articles published in English up to December 28, 2015. RCTs and systematic reviews of RCTs of MIS versus open spine surgery were evaluated for three particular entities: Cervical disc herniation, lumbar disc herniation, and posterior lumbar fusion., Results: A total of 17 RCTs were identified, along with six systematic reviews. For cervical disc herniation, MIS provided no difference in overall function, arm pain relief, or long-term neck pain. In lumbar disc herniation, MIS was inferior in providing leg/low back pain relief, rehospitalization rates, quality of life improvement, and exposed the surgeon to >10 times more radiation in return for shorter hospital stay and less surgical site infection. In posterior lumbar fusion, MIS transforaminal lumbar interbody fusion (TLIF) had significantly reduced 2-year societal cost, fewer medical complications, reduced time to return to work, and improved short-term Oswestry Disability Index scores at the cost of higher revision rates, higher readmission rates, and more than twice the amount of intraoperative fluoroscopy., Conclusion: The highest levels of evidence do not support MIS over open surgery for cervical or lumbar disc herniation. However, MIS TLIF demonstrates advantages along with higher revision/readmission rates. Regardless of patient indication, MIS exposes the surgeon to significantly more radiation; it is unclear how this impacts patients. These results should optimize informed decision-making regarding MIS versus open spine surgery, particularly in the current advertising climate greatly favoring MIS., Competing Interests: There are no conflicts of interest.

Objectives: This systematic review aims to investigate the incidence and prevalence of type 2 diabetes mellitus (T2DM) in patients with HIV infection in African populations., Setting: Only studies reporting data from Africa were included., Participants: A systematic search was conducted using four databases for articles referring to HIV infection and antiretroviral therapy, and T2DM in Africa. Articles were excluded if they reported data on children, animals or type 1 diabetes exclusively., Main Outcome Measures: Incidence of T2DM and prevalence of T2DM. Risk ratios were generated for pooled data using random effects models. Bias was assessed using an adapted Cochrane Collaboration bias assessment tool., Results: Of 1056 references that were screened, only 20 were selected for inclusion. Seven reported the incidence of T2DM in patients with HIV infection, eight reported the prevalence of T2DM in HIV-infected versus uninfected individuals and five reported prevalence of T2DM in HIV-treated versus untreated patients. Incidence rates ranged from 4 to 59 per 1000 person years. Meta-analysis showed no significant differences between T2DM prevalence in HIV-infected individuals versus uninfected individuals (risk ratio (RR) =1.61, 95% CI 0.62 to 4.21, p=0.33), or between HIV-treated patients versus untreated patients (RR=1.38, 95% CI 0.66 to 2.87, p=0.39), and heterogeneity was high in both meta-analyses (I 2 =87% and 52%, respectively)., Conclusions: Meta-analysis showed no association between T2DM prevalence and HIV infection or antiretroviral therapy; however, these results are limited by the high heterogeneity of the included studies and moderate-to-high risk of bias, as well as, the small number of studies included. There is a need for well-designed prospective longitudinal studies with larger population sizes to better assess incidence and prevalence of T2DM in African patients with HIV. Furthermore, screening for T2DM using gold standard methods in this population is necessary., Trial Registration Number: PROSPERO42016038689., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Relict leopard frog ( Rana [ Lithobates ] onca ) tadpoles were obtained shortly after hatching at Gosner stage 25 and raised in aquaria maintained at 15, 20, 25, 30 and 35°C. Development was arrested in the 15°C group, and survivorship declined to 64% after 191 days. However, 80% of the surviving larvae remained alive after the temperature was increased to 25°C. Of these, 96% reached metamorphosis. Survivorship of the 20, 25 and 30°C acclimation groups was 82, 94 and 66%, respectively, whereas none survived at 35°C. Time to metamorphosis was significantly shorter for the 25°C group (67 ± 1 days), followed by the 30°C (98 ± 2 days) and 20°C (264 ± 7 days) groups. A linear 66 cm thermal gradient was used to identify temperature ranges selected by tadpoles in the different acclimation groups. Five 10°C gradients (10-20, 15-25, 20-30, 25-35 and 30-40°C) were used, and time spent in the cooler, middle and warmer thirds of the gradient was compared for 10 individuals from each acclimation group. In the coolest gradient, tadpoles from all acclimation groups selected the warmer third (>17°C) of the gradient. In the warmer gradients, tadpoles from the 20 and 25°C acclimation groups selected temperatures <29°C, while those from the 30°C acclimation group selected temperatures <33°C. Maximal burst speed for all groups was greater at experimental temperatures of 25 than 15°C. Efforts to reintroduce this species to its historical range should select habitats where water temperatures between 25 and 30°C are available during the post-hatching period.