Automated analysis of scattering-based light sheet microscopy images of anal squamous intraepithelial lesions.

We developed an algorithm for automatically analyzing scattering-based light sheet microscopy (sLSM) images of anal squamous intraepithelial lesions. We developed a method for automatically segmenting sLSM images for nuclei and calculating seven features: nuclear intensity, intensity slope as a function of depth, nuclear-to-nuclear distance, nuclear-to-cytoplasm ratio, cell density, nuclear area, and proportion of pixels corresponding to nuclei. 187 images from 80 anal biopsies were used for feature analysis and classifier development. The automated nuclear segmentation method provided reliable performance with the precision of 0.97 and recall of 0.91 when compared with the manual segmentation. Among the seven features, six showed statistically significant differences between high-grade squamous intraepithelial lesion (HSIL) and non-HSIL (non-dysplastic or low-grade squamous intraepithelial lesion, LSIL). A classifier using linear support vector machine (SVM) achieved promising performance in diagnosing HSIL versus non-HSIL: sensitivity of 90%, specificity of 70%, and area under the curve (AUC) of 0.89 for per-image diagnosis, and sensitivity of 90%, specificity of 80%, and AUC of 0.92 for per-biopsy diagnosis.

Effects of implant precoating and fat contamination on the stability of the tibial baseplate.

BACKGROUND: Approximately 5% of primary total knee arthroplasty patients require revision within 10 years, often due to distal component loosening. Application of a thin layer of PMMA cement as precoating on the tibial component aims to prevent aseptic loosening. This study investigates the impact of precoating and fat contamination on tibial baseplate stability. METHODS: Two groups of NexGen® stemmed tibial implants (size 4) were studied: Option implants (N = 12) and PMMA Precoat implants (N = 12). Each implant design was divided into two subgroups, (N = 6), with one subgroup featuring bone marrow fat at the implant-cement interface and the other without contamination. In a mechanical testing machine, the implants underwent uniaxial loading for 20,000 cycles, while recording vertical micromotion and migration of the tibial baseplates. Subsequently, a push-out test assessed fixation strength at the cement interfaces. Results were compared using non-parametric statistics and presented as median and min-to-max ranges. RESULTS: Option implants exhibited higher micromotion in dry conditions compared to precoated implants (p = 0.03). Under contamination, both designs demonstrated similar micromotion values. Fixation strength did not significantly differ between designs under dry, uncontaminated conditions (p > 0.99). However, under contaminated conditions, the failure load for the non-coated Option implant was nearly half that of the uncontaminated counterparts (3517 N, 2603-4367 N vs 7531 N, 5163-9000 N; p = 0.002). Precoat implants displayed less susceptibility to fat contamination (p = 0.30). CONCLUSION: NexGen® implant PMMA precoating might reduce the risk of aseptic loosening and revision surgery in case of eventual bone-marrow fat contamination.

Scattering-Based Light-Sheet Microscopy Imaging of Human Papillomavirus-Associated Squamous Lesions of the Anal Canal: A Proof-of-Principle Study.

Demand for anal cancer screening is expected to rise following the recent publication of the Anal Cancer-HSIL Outcomes Research trial, which showed that treatment of high-grade squamous intraepithelial lesions significantly reduces the rate of progression to anal cancer. While screening for human papillomavirus-associated squamous lesions in the cervix is well established and effective, this is less true for other sites in the lower anogenital tract. Current anal cancer screening and prevention rely on high-resolution anoscopy with biopsies. This procedure has a steep learning curve for providers and may cause patient discomfort. Scattering-based light-sheet microscopy (sLSM) is a novel imaging modality with the potential to mitigate these challenges through real-time, microscopic visualization of disease-susceptible tissue. Here, we report a proof-of-principle study that establishes feasibility of dysplasia detection using an sLSM device. We imaged 110 anal biopsy specimens collected prospectively at our institution's dysplasia clinic (including 30 nondysplastic, 40 low-grade squamous intraepithelial lesion, and 40 high-grade squamous intraepithelial lesion specimens) and found that these optical images are highly interpretable and accurately recapitulate histopathologic features traditionally used for the diagnosis of human papillomavirus-associated squamous dysplasia. A reader study to assess diagnostic accuracy suggests that sLSM images are noninferior to hematoxylin and eosin images for the detection of anal dysplasia (sLSM accuracy = 0.87; hematoxylin and eosin accuracy = 0.80; P = .066). Given these results, we believe that sLSM technology holds great potential to enhance the efficacy of anal cancer screening by allowing accurate sampling of diagnostic tissue at the time of anoscopy. While the current imaging study was performed on ex vivo biopsy specimens, we are currently developing a handheld device for in vivo imaging that will provide immediate microscopic guidance to high-resolution anoscopy providers.

Cementing techniques for total knee arthroplasty in Norwegian hospitals; a questionnaire-based study.

BACKGROUND: Cementing technique in total knee arthroplasty (TKA) may influence implant survival. There is limited knowledge about the results with clinically used techniques. The aim of this study was to investigate cementing techniques for TKA in Norwegian hospitals, to compare widely used techniques to recommendations from the literature, and to investigate variation within hospitals. METHODS: A questionnaire requesting information about cementing techniques were distributed to all Norwegian orthopedic surgeons performing TKAs regularly in 2020. Data was analyzed using descriptive statistical methods. RESULTS: We acquired 121 responses out of 257 surgeons. They were from 45 out of 56 hospitals, and at least half of the TKA surgeons from 20 hospitals, constituting 79 surgeons. All responders used pulsatile lavage. Cement application to both the tibial plateau and stem (full cementation) was practiced by 61%. Application of cement to both implant and bone was done by 70% of surgeons. Techniques to improve cement penetration were used by 86%. Only 35% of surgeons aimed to get a cement mantle thickness between 3-5 mm. Flexing the knee joint to remove excess cement was done by 82%. We found that in 55% of 20 hospitals the surgeons did not agree on the use of common guidelines in their ward. CONCLUSIONS: The majority of the responders used recommended techniques from the literature when cementing TKA. At more than half of the eligible hospitals, surgeons disagreed about their hospitals' use of common guidelines. Focusing on developing evidence-based guidelines would be beneficial for TKA-quality.

Understanding Sexual and Gender Minority Populations and Organ-Based Screening Recommendations for Human Papillomavirus-Related Cancers.

OBJECTIVES: Sexual gender minority (SGM) populations are at risk for human papillomavirus (HPV)-related cancers of the anogenital tract and oropharynx and often face barriers to health care. The goals of this document are to clarify language to provide inclusive care for SGM populations and to provide recommendations for screening and prevention of HPV-related cancers in SGM populations. MATERIALS AND METHODS: An expert committee convened by the American Society for Colposcopy and Cervical Pathology performed a narrative review of the literature through February 2023. A comprehensive MEDLINE database search was performed for relevant studies. The literature review was divided into categories by organ/topic and by SGM population. Given the variability in available data for several of the categories, recommendations were made based on national guidelines where appropriate or expert opinion where there were less data to support risk-based guidelines. RESULTS: Definitions and terminology relevant to SGM populations are presented. The authors advocate the adoption of sexual orientation gender identity data collection and an organ-based screening approach, which is possible with knowledge of patient anatomy, sexual behaviors, and clinical history. This includes screening for cervical cancer per national recommendations, as well as screening for anal, vulvar, vaginal, penile, and oral cancers based on risk factors and shared clinical decision making. The authors recommend consideration of HPV vaccination in all SGM individuals up to age 45 years old who are at risk. CONCLUSIONS: An organ-based screening approach is part of a global strategy to create an inclusive care environment and mitigate barriers to screening and prevention of HPV-mediated cancers in SGM populations.

Executive Summary of the Lower Anogenital Tract Cancer Evidence Review Conference.

The Centers for Disease Control and Prevention sponsored a project conducted by the American College of Obstetricians and Gynecologists to develop educational materials for clinicians on the prevention and early diagnosis of gynecologic cancers. For this final module, focusing on the cancers of the lower anogenital tract (vulva, vagina, and anus), a panel of experts in evidence assessment from the Society for Academic Specialists in General Obstetrics and Gynecology, ASCCP, and the Society of Gynecologic Oncology reviewed relevant literature and current guidelines. Panel members conducted structured literature reviews, which were then reviewed by other panel members. Representatives from stakeholder professional and patient advocacy organizations met virtually in September 2022 to review and provide comment. This article is the executive summary of the review. It covers prevention, early diagnosis, and special considerations of lower anogenital tract cancer. Knowledge gaps are summarized to provide guidance for future research.

Truth or DARE (Digital Anal Rectal Examination): Gynecologist Viewpoints on Anal Cancer Screening.

METHODS: The authors conducted a survey for practicing gynecologists recruited through academic institutions, professional societies, and professional groups on social media resulting in 196 respondents. The survey, fielded between January and June 2022, included questions on knowledge, attitudes, training, and practices regarding anal cancer prevention (ACP). Descriptive statistics and χ 2 analysis were completed. RESULTS: In terms of knowledge regarding ACP, over 80% of respondents identified certain clinical indications for anal cancer screening. However, only 36% respondents selected the 3 correct ACP screening tools. Twenty-seven (13.9%) respondents reported receiving training on ACP in medical school, whereas 50 (25.9%) reported receiving training during residency. Only 21% of respondents reported that they perform anal cytology, and 32% reported that they perform digital anal rectal examinations. One hundred thirty-six respondents (75.56%) affirmed that they needed additional training on ACP to be able to provide this service to their patients, and 95 (53.1%) stated they were extremely likely to participate in ACP training if given the opportunity. CONCLUSION: Although a limited proportion of practicing gynecologists are trained in ACP, there is willingness to participate in training if it were made available and to incorporate ACP into their practices.

Cervical Cancer Screening: Evolution of National Guidelines and Current Recommendations.

Cancer of the cervix is preventable through vaccination against human papillomavirus and by screening and treatment of cervical precancers. Cervical cancer screening has evolved since the Pap smear was first discovered in the 1920s. Current guidelines from the US Preventive Services Task Force and the American Cancer Society incorporate the use of cervical cytology and high-risk human papillomavirus tests performed every 3 to 5 years for screening in average-risk asymptomatic patients. Testing should begin at age 21 to 25 years old and stop at 65 years old if sufficient cessation criteria has been met.

Retrospective Screening of Clinical Samples for Monkeypox Virus DNA, California, USA, 2022.

We retrospectively screened oropharyngeal and rectal swab samples originally collected in California, USA, for Chlamydia trachomatis and Neisseria gonorrhoeae testing for the presence of monkeypox virus DNA. Among 206 patients screened, 17 (8%) had samples with detectable viral DNA. Monkeypox virus testing from mucosal sites should be considered for at-risk patients.

Investigation of different wavelengths for scattering-based light sheet microscopy.

Scattering-based light sheet microscopy (sLSM) is a microscopy technique that can visualize cellular morphologic details based on the scattering signal. While sLSM was previously shown to image animal tissues ex vivo at a cellular resolution, the wavelength used was chosen based on other in vivo microscopy technologies rather than through a comparison of the sLSM imaging performance between different wavelengths. In this paper, we report the development of a multi-wavelength sLSM setup that facilitates the investigation of different wavelengths for sLSM imaging. Preliminary results of imaging human anal tissues ex vivo showed that the sLSM setup allowed for comparisons of the cellular imaging performance at the same tissue location between different wavelengths. Both the quantitative analysis of the image contrast and the visual assessment by a pathologist showed that the imaging depth increased with wavelength, and the imaging depth increase was most notable around 600 nm. The preliminary results showed that the multi-wavelength sLSM setup could be useful in identifying the optimal wavelength for the specific tissue type.

Challenges Associated With Cervical Cancer Screening and Management in Obese Women: A Provider Perspective.

OBJECTIVES: Obese women are at increased risk of cervical cancer, partly due to missed detection of cervical precancers during routine cervical cancer screening. We administered a clinician survey to better understand specific challenges and identify potential solutions to performing cervical cancer screening and management in obese women. MATERIALS AND METHODS: We administered a web-based survey to 2,319 members of the American Society of Colposcopy and Cervical Pathology including questions related to challenges associated with cervical sampling and visualization in obese compared with normal weight women and potential strategies for improvement. We summarized providers' responses using descriptive statistics and used Fisher exact tests to evaluate associations between provider characteristics and challenges with cervical sampling, visualization, and biopsy. RESULTS: Of the 240 providers that completed the survey, 89% and 93% reported that cervical sampling and visualization are more challenging in obese women, respectively, whereas 80% reported that taking a biopsy was more challenging. Commonly reported barriers included vaginal prolapse, difficulty visualizing and accessing the cervix, and lack of long enough sampling devices and large enough speculums. Frequently used techniques to improve sampling and visualization included use of a condom or examination glove finger to sheath a speculum and using a tenaculum. Most providers identified training for cervical sampling and colposcopy in obese women as a learning gap, and only 8% reported receiving such training. CONCLUSIONS: Cervical cancer screening and management are more challenging in obese compared with normal weight women. Major barriers to cervical sampling and visualization included lack of adequately sized equipment and lack of education and training.

HIV Status and Other Risk Factors for Prevalent and Incident Sexually Transmitted Infection during Pregnancy (2000-2014).

Background: Sexually transmitted infections (STIs) are associated with adverse birth outcomes. Current prenatal STI screening guidelines define "risk" without explicit consideration of HIV status. Our objective was to test the hypothesis that HIV status is associated with bacterial STI in pregnant women. Methods: We designed a retrospective cohort study to identify pregnant women with HIV who delivered at our facility during 2000-2014. HIV+ women were compared to HIV- women with matching by year of delivery. Logistic regression was used to model adjusted odds of prevalent and incident STI. Prevalent STI was defined as chlamydia (CT), gonorrhea (GC), syphilis, or trichomoniasis detected on an initial prenatal screening test and incident STI as a newly positive result following a negative prenatal test. Results: The cohort included 432 women, 210 HIV+ and 222 HIV-. Most pregnant women were screened for STI (92% of HIV+ women and 74% of HIV- women). STI rates were high and particularly elevated in HIV+ women: 29% vs 18% (p=0.02), for prevalent STI and 11% vs 2% (p<0.001) for incident STI. Risk factors for prevalent STI were as follows: HIV status (aOR 3.0, CI: 1.4-6.4), Black race (aOR 2.7, 95% CI: 1.1-6.6), and more recent delivery (2007-2014 compared to 2000-2006) (aOR 2.3, CI: 1.1-4.7). HIV status was an independent risk factor for incident STI (aOR 7.2, CI: 2.1-25.0). Conclusion: Pregnant women who delivered in our center had high STI rates. Since HIV infection was independently associated with prevalent and incident STI, prenatal screening guidelines may need to incorporate HIV status as a high-risk group for repeat testing.

HIV Status and Contraceptive Utilization among Women in Cameroon.

OBJECTIVE: We examined patterns of contraceptive utilization by HIV status among women in Cameroon, hypothesizing that women living with HIV would utilize contraception at higher rates than their HIV-negative peers. METHODS: Deidentified, clinical data from the Cameroon Baptist Convention Health Services (2007-2013) were analyzed (N = 8995). Frequencies compared outcomes between women living with HIV (15.1%) and uninfected women. Multivariate analyses examined associates of contraceptive utilization and desire to become pregnant. RESULTS: Contraceptive utilization was associated with higher education, living with HIV, monogamy, and higher parity ( P < .001). Women living with HIV had 66% higher odds of using contraceptives than their negative peers (odds ratio [OR]: 1.66, confidence interval [CI]: 1.45-1.91, P < .001). Polygamous women had 37% lower odds of using contraceptives compared to monogamous women (OR: 0.63, 95% CI: 0.52-0.75, P < .001). CONCLUSION: Increasing contraceptive utilization in resource-constrained settings should be a priority for clinicians and researchers. Doing so could improve population health by reducing HIV transmission between partners and from mother to child.

Risk of Cervical Intraepithelial Neoplasia 2 or Worse by Cytology, Human Papillomavirus 16/18, and Colposcopy Impression: A Systematic Review and Meta-analysis.

OBJECTIVE: To calculate pooled risk estimates for combinations of cytology result, human papillomavirus (HPV) 16/18 genotype and colposcopy impression to provide a basis for risk-stratified colposcopy and biopsy practice. DATA SOURCE: A PubMed search was conducted on June 1, 2016, and a ClinicalTrials.gov search was conducted on June 9, 2018, using key words such as "uterine cervical neoplasms," "cervical cancer," "mass screening," "early detection of cancer," and "colposcopy." METHODS OF STUDY SELECTION: Eligible studies must have included colposcopic impression and either cytology results or HPV 16/18 partial genotype results as well as a histologic biopsy diagnosis from adult women. Manuscripts were reviewed for the following: cytology, HPV status, and colposcopy impression as well as age, number of women, and number of cervical intraepithelial neoplasia (CIN) 2, CIN 3, and cancer cases. Strata were defined by the various combinations of cytology, genotype, and colposcopic impression. TABULATION, INTEGRATION, AND RESULTS: Of 340 abstracts identified, nine were eligible for inclusion. Data were also obtained from three unpublished studies, two of which have since been published. We calculated the risk of CIN 2 or worse and CIN 3 or worse based on cytology, colposcopy, and HPV 16/18 test results. We found similar risk patterns across studies in the lowest risk groups such that risk estimates were similar despite different referral populations and study designs. Women with a normal colposcopy impression (no acetowhitening), less than high-grade squamous intraepithelial lesion cytology, and HPV 16/18-negative were at low risk of prevalent precancer. Women with at least two of the following: high-grade squamous intraepithelial lesion cytology, HPV16- or HPV18-positive, and high-grade colposcopic impression were at highest risk of prevalent precancer. CONCLUSION: Our results support a risk-based approach to colposcopy and biopsy with modifications of practice at the lowest and highest risk levels.

Evidence-Based Consensus Recommendations for Colposcopy Practice for Cervical Cancer Prevention in the United States.

The American Society for Colposcopy and Cervical Pathology (ASCCP) Colposcopy Standards recommendations address the role of colposcopy and directed biopsy for cervical cancer prevention in the United States (US). The recommendations were developed by an expert working group appointed by ASCCP's Board of Directors. An extensive literature review was conducted and supplemented by a systematic review and meta-analysis of unpublished data. In addition, a survey of practicing colposcopists was conducted to assess current colposcopy practice in the US. Recommendations were approved by the working group members, and the final revisions were made based on comments received from the public. The recommendations cover terminology, risk-based colposcopy, colposcopy procedures, and colposcopy adjuncts. The ASCCP Colposcopy Standards recommendations are an important step toward raising the standard of colposcopy services delivered to women in the US. Because cervical cancer screening programs are currently undergoing important changes that may affect colposcopy performance, updates to some of the current recommendations may be necessary in the future.

ASCCP Colposcopy Standards: Risk-Based Colposcopy Practice.

OBJECTIVES: The American Society for Colposcopy and Cervical Pathology (ASCCP) Colposcopy Standards recommendations address the role of and approach to colposcopy for cervical cancer prevention in the United States. MATERIALS AND METHODS: The recommendations were developed by an expert working group appointed by ASCCP's Board of Directors. This article describes the rationale, evidence, and recommendations related to risk-based colposcopy practice. RESULTS: Women referred to colposcopy have a wide range of underlying precancer risk, which can be estimated by referral screening tests including cytology and human papillomavirus testing, in conjunction with the colposcopic impression. Multiple targeted biopsies, at least 2 and up to 4, are recommended to improve detection of prevalent precancers. At the lowest end of the risk spectrum, untargeted biopsies are not recommended, and women with a completely normal colposcopic impression can be observed. At the highest end of the risk spectrum, immediate treatment is an alternative to biopsy confirmation. CONCLUSIONS: Assessing the risk of cervical precancer at the colposcopy visit allows for modification of colposcopy procedures consistent with a woman's risk. Implementation of these recommendations is expected to lead to improved detection of cervical precancers at colposcopy, while providing more reassurance of negative colposcopy results.

ASCCP Colposcopy Standards: Role of Colposcopy, Benefits, Potential Harms, and Terminology for Colposcopic Practice.

OBJECTIVES: The American Society for Colposcopy and Cervical Pathology Colposcopy Standards address the role of and approach to colposcopy and biopsy for cervical cancer prevention in the United States. Working Group 1 was tasked with defining the role of colposcopy, describing benefits and potential harms, and developing an official terminology. METHODS: A systematic literature review was performed. A national survey of American Society for Colposcopy and Cervical Pathology members provided input on current terminology use. The 2011 International Federation for Cervical Pathology and Colposcopy terminology was used as a template and modified to fit colposcopic practice in the United States. For areas without data, expert consensus guided the recommendation. Draft recommendations were posted online for public comment and presented at an open session of the 2017 International Federation for Cervical Pathology and Colposcopy World Congress for further comment. All comments were considered for the final version. RESULTS: Colposcopy is used in the evaluation of abnormal or inconclusive cervical cancer screening tests. Colposcopy aids the identification of cervical precancers that can be treated, and it allows for conservative management of abnormalities unlikely to progress. The potential harms of colposcopy include pain, psychological distress, and adverse effects of the procedure. A comprehensive colposcopy examination should include documentation of cervix visibility, squamocolumnar junction visibility, presence of acetowhitening, presence of a lesion(s), lesion(s) visibility, size and location of lesions, vascular changes, other features of lesion(s), and colposcopic impression. Minimum criteria for reporting include squamocolumnar junction visibility, presence of acetowhitening, presence of a lesion(s), and colposcopic impression. CONCLUSIONS: A recommended terminology for use in US colposcopic practice was developed, with comprehensive and minimal criteria for reporting.

ASCCP Colposcopy Standards: Colposcopy Quality Improvement Recommendations for the United States.

OBJECTIVES: The American Society for Colposcopy and Cervical Pathology (ASCCP) Colposcopy Standards recommendations address the role of and approach to colposcopy and biopsy for cervical cancer prevention in the United States. The recommendations were developed by an expert working group appointed by ASCCP's Board of Directors. The ASCCP Quality Improvement Working Group developed evidence-based guidelines to promote best practices and reduce errors in colposcopy and recommended indicators to measure colposcopy quality. MATERIALS AND METHODS: The working group performed a systematic review of existing major society and national guidelines and quality indicators. An initial list of potential quality indicators was developed and refined through successive iterative discussions, and draft quality indicators were proposed. The draft recommendations were then reviewed and commented on by the entire Colposcopy Standards Committee, posted online for public comment, and presented at the International Federation for Cervical Pathology and Colposcopy 2017 World Congress for further comment. All comments were considered, additional adjustments made, and the final recommendations approved by the entire Task Force. RESULTS: Eleven quality indicators were selected spanning documentation, biopsy protocols, and time intervals between index screening tests and completion of diagnostic evaluation. CONCLUSIONS: The proposed quality indicators are intended to serve as a starting point for quality improvement in colposcopy at a time when colposcopy volume is decreasing and individual procedures are becoming technically more difficult to perform.

ASCCP Colposcopy Standards: How Do We Perform Colposcopy? Implications for Establishing Standards.

OBJECTIVES: The American Society for Colposcopy and Cervical Pathology (ASCCP) Colposcopy Standards recommendations address the role of and approach to colposcopy and biopsy for cervical cancer prevention in the United States. The recommendations were developed by an expert working group appointed by ASCCP's Board of Directors. Working group 3 defined colposcopy procedure guidelines for minimum and comprehensive colposcopy practice and evaluated the use of colposcopy adjuncts. MATERIALS AND METHODS: The working group performed a systematic literature review to identify best practices in colposcopy methodology and to evaluate the use of available colposcopy adjuncts. The literature provided little evidence to support specific elements of the procedure. The working group, therefore, implemented a national survey of current and recent ASCCP members to evaluate common elements of the colposcopy examination. The findings of this survey were modified by expert consensus from the ASCCP Colposcopy Standards Committee members to create guidelines for performing colposcopy. The draft recommendations were posted online for public comment and presented at an open session of the International Federation for Cervical Pathology and Colposcopy 2017 World Congress for further comment. All comments were considered in the development of final recommendations. RESULTS: Minimum and comprehensive colposcopy practice guidelines were developed. These guidelines represent recommended practice in all parts of the examination including the following: precolposcopy evaluation, performing the procedure, documentation of findings, biopsy practice, and postprocedure follow-up. CONCLUSIONS: These guidelines are intended to serve as a guide to standardize colposcopy across the United States.