Shining Light on Osteoarthritis: Spatially Offset Raman Spectroscopy as a Window into Cartilage Health.

Articular cartilage is a complex tissue, and early detection of osteoarthritis (OA) is crucial for effective treatment. However, current imaging modalities lack molecular specificity and primarily detect late-stage changes. In this study, we propose the use of spatially offset Raman spectroscopy (SORS) for noninvasive, depth-dependent, and molecular-specific diagnostics of articular cartilage. We demonstrate the potential of SORS to penetrate deep layers of cartilage, providing a comprehensive understanding of disease progression. Our SORS measurements were characterized and validated through mechanical and histological techniques, revealing strong correlations between spectroscopic measurements and both Young's modulus and depth of cartilage damage. By longitudinally monitoring enzymatically degraded condyles, we further developed a depth-dependent damage-tracking method. Our analysis revealed distinct components related to sample depth and glycosaminoglycan (GAG) changes, offering a comprehensive picture of cartilage health. Collectively, these findings highlight the potential of SORS as a valuable tool for enhancing OA management and improving patient outcomes.

Noninvasive measurement of tracer extraction efficiency in tissue, illustrated with Tc-99m-MAG3.

OBJECTIVE: The aim of this study is to develop a noninvasive technique for measuring tissue tracer extraction efficiency ( E ) and illustrate it for Tc-99m-mercaptoacetyltriglycine (MAG3) and kidney. METHODS: E was measured in 10 patients with normal MAG3 renography. E is the ratio of tissue clearance-to-blood flow ( Ki/F ). For single-photon tracers, attenuation constants are unknown, so Ki and F cannot be separately measured. However, by deriving attenuation-uncorrected Ki' and F' from the same regions of interests (ROIs), these constants cancel out, giving E . Using a lung ROI for blood activity, F was measured from first-pass and Ki' from Gjedde-Patlak-Rutland (GPR) analysis up to 130 s. Because of interference from right ventricle, a left ventricular ROI (LV) is unsuitable for F' but was used in GPR analysis, making an adjustment for the ratio of respective blood pool signals arising from lung and LV ROIs in early frames (60-90 s). RESULTS: A lung ROI underestimates F' by 4% at normal LV function. Chest wall interstitial activity ( I ), which does not affect F' , amounted to 53 and 30% of the lung and LV signals at 20 min, and 12 and 6% at 130 s, resulting in underestimations of Ki of 4 and 2%, respectively. Ignoring these opposing errors, E based on lung ROI for left and right kidneys was 43.5 (SD 8)% and 47.3 (9)%, and based on LV ROI for GPR analysis was 44.5 (10.9)% and 48.3 (10.6)%. CONCLUSION: E can be measured by combining blood flow from first-pass with clearance from GPR analysis, and has potential value both clinically and in clinical research.

CellSNAP: a fast, accurate algorithm for 3D cell segmentation in quantitative phase imaging.

Significance: Three-dimensional quantitative phase imaging (QPI) has rapidly emerged as a complementary tool to fluorescence imaging, as it provides an objective measure of cell morphology and dynamics, free of variability due to contrast agents. It has opened up new directions of investigation by providing systematic and correlative analysis of various cellular parameters without limitations of photobleaching and phototoxicity. While current QPI systems allow the rapid acquisition of tomographic images, the pipeline to analyze these raw three-dimensional (3D) tomograms is not well-developed. We focus on a critical, yet often underappreciated, step of the analysis pipeline that of 3D cell segmentation from the acquired tomograms. Aim: We report the CellSNAP (Cell Segmentation via Novel Algorithm for Phase Imaging) algorithm for the 3D segmentation of QPI images. Approach: The cell segmentation algorithm mimics the gemstone extraction process, initiating with a coarse 3D extrusion from a two-dimensional (2D) segmented mask to outline the cell structure. A 2D image is generated, and a segmentation algorithm identifies the boundary in the x-y plane. Leveraging cell continuity in consecutive z-stacks, a refined 3D segmentation, akin to fine chiseling in gemstone carving, completes the process. Results: The CellSNAP algorithm outstrips the current gold standard in terms of speed, robustness, and implementation, achieving cell segmentation under 2 s per cell on a single-core processor. The implementation of CellSNAP can easily be parallelized on a multi-core system for further speed improvements. For the cases where segmentation is possible with the existing standard method, our algorithm displays an average difference of 5% for dry mass and 8% for volume measurements. We also show that CellSNAP can handle challenging image datasets where cells are clumped and marred by interferogram drifts, which pose major difficulties for all QPI-focused AI-based segmentation tools. Conclusion: Our proposed method is less memory intensive and significantly faster than existing methods. The method can be easily implemented on a student laptop. Since the approach is rule-based, there is no need to collect a lot of imaging data and manually annotate them to perform machine learning based training of the model. We envision our work will lead to broader adoption of QPI imaging for high-throughput analysis, which has, in part, been stymied by a lack of suitable image segmentation tools.

Prospective Evaluation of the Clinical Benefits of a Novel Tattoo-less Workflow for Nonspine Bone Stereotactic Body Radiation Therapy: Integrating Surface-Guidance With Triggered Imaging Reduces Treatment Time and Eliminates the Need for Tattoos.

PURPOSE: Oligometastatic disease has expanded the indications for nonspine bone stereotactic body radiation therapy (NSB SBRT). We investigated whether optical surface monitoring systems (OSMS) could enable tattoo-less setup and substitute for 2-dimensional/3-dimensional or cone beam computed tomography (CBCT)-based mid-imaging in NSB SBRT. METHODS AND MATERIALS: OSMS was incorporated in parallel with an existing workflow using pretreatment CBCT and 2-dimensional/3-dimensional kV/kV mid-imaging beginning November 2019. The ability of OSMS to detect out-of-tolerance (>2 mm/>2°) and commanded couch shifts was analyzed. A workflow incorporating OSMS reference captures, CBCT for pretreatment verification, and OSMS/triggered imaging (TI) for intrafraction monitoring was developed for rib/sternum SBRT beginning November 2021 and all NSB SBRT beginning February 2022. Treatment time and CBCT-related radiation dose between the OSMS and the non-OSMS intrafraction monitoring group was analyzed pre- and post-OSMS/TI workflow adoption. All fractions were analyzed through statistical process control with use of an XmR chart of treatment time per quarter from February 2019 to February 2023. Special cause rules were based on Institute for Healthcare Improvement criteria. RESULTS: From February 2019 to February 2023, 1993 NSB SBRT fractions were delivered, including 234 rib, 109 sternum, 214 ilium, and 682 multisite. Over 20 commanded shifts, OSMS could detect 2-mm shifts to within 0.4 mm 67% of the time and 0.8 mm 95% of the time. All NSB SBRT sites showed significant reductions in treatment time, including the greatest improvement in rib total treatment (21.6-13.4 minutes; P = 1.16 × 10-17) and beam time (7.9-3.2 minutes; P = 7.32 × 10-27). Significant reductions in CBCT-related radiation were also observed for several NSB sites. These process improvements were associated with OSMS adoption. CONCLUSIONS: Adoption of a novel NSB SBRT workflow incorporating OSMS/TI for bone intrafraction motion monitoring reduced treatment time and CBCT-related radiation exposure while also allowing for more continuous intrafraction motion monitoring for NSB SBRT. OSMS/TI enabled the transition to a tattoo-less workflow.

Percutaneous Aortoiliac Thromboendarterectomy for Acute Limb Ischemia.

Aortoiliac occlusive disease (AIOD) can occur from either chronic, progressive atherosclerotic disease, acute on chronic thrombosis or acute arterial embolism, and can all result in limb ischemia. Bypass surgery had long been the gold standard for treatment for AIOD, however, with advances in endovascular techniques, minimally invasive treatment of aortoiliac lesions has become the first line choice of management in many cases. Herein, we describe a case of utilizing the Inari ClotTriever to perform aortoiliac mechanical thrombectomy and the ARTIX thrombectomy system to perform an embolectomy the superficial femoral artery, highlighting new therapies to treat AIOD.

Errors in measurement of glomerular filtration rate using the slope-intercept technique and their identification.

BACKGROUND: GFR measured from plasma sampling may be expressed as slope-intercept GFR (SI-GFR) and scaled to body surface area (mGFR/BSA) or as GFR per unit extracellular fluid volume (mGFR/ECV), which is based only on half-time. Measurement errors comprise 3 categories. Pre-injection error arises from error in administered marker and is suspected when mGFR/BSA and mGFR/ECV disagree. Injection errors include 'tissued' injections. Post-injection errors include inaccurate sample timing, inaccurate pipetting, sample haemolysis and sampling through long IV lines through which marker was administered. The aim of the study was to evaluate the impact of errors on mGFR. METHODS: We compared mGFR/BSA with mGFR/ECV in 898 patients undergoing routine investigation. To investigate post-injection error, we took two further patient datasets with r values (correlation coefficient of the 3-sample fit) of 1.0 and introduced errors, in isolation, into each of the 3 recorded sample values, as follows: pipetting (volume) errors of -20%, -10%, -5%, 5%, 10% and 20%, and timing errors of -15 min, -10 min, -5 min, 5 min, 10 min and 15 min. RESULTS: The correlation between mGFR/BSA and mGFR/ECV was close and independent of r. Post-injection error depended on the time of the sample in which it occurred. r correlated poorly with error magnitude for both volume and timing errors. When a 'rogue' sample is suspected its error needed to be substantial for it to be identified by single sample estimates applied to the other samples. CONCLUSION: SI-GFR is resistant to post-injection timing and volume errors but not to pre-injection error.

Shining Light on Osteoarthritis: Spatially Offset Raman Spectroscopy as a Window into Cartilage Health.

Articular cartilage is a complex tissue, and early detection of osteoarthritis (OA) is crucial for effective treatment. However, current imaging modalities lack molecular specificity and primarily detect late-stage changes. In this study, we propose the use of Spatially Offset Raman Spectroscopy (SORS) for non-invasive, depth-dependent, and molecular-specific diagnostics of articular cartilage. We demonstrate the potential of SORS to penetrate deep layers of cartilage, providing a comprehensive understanding of disease progression. Our SORS measurements were characterized and validated through mechanical and histological techniques, revealing strong correlations between spectroscopic measurements and both Young's modulus and depth of cartilage damage. By longitudinally monitoring enzymatically degraded condyles, we further developed a depth-dependent damage-tracking method. Our analysis revealed distinct components related to sample depth and glycosaminoglycan (GAG) changes, offering a comprehensive picture of cartilage health. Collectively, these findings highlight the potential of SORS as a valuable tool for enhancing OA management and improving patient outcomes.

CellSNAP: A fast, accurate algorithm for 3D cell segmentation in quantitative phase imaging.

Quantitative phase imaging (QPI) has rapidly emerged as a complementary tool to fluorescence imaging, as it provides an objective measure of cell morphology and dynamics, free of variability due to contrast agents. In particular, three-dimensional (3D) tomographic imaging of live cells has opened up new directions of investigation by providing systematic and correlative analysis of various cellular parameters without limitations of photobleaching and phototoxicity. While current QPI systems allow the rapid acquisition of tomographic images, the pipeline to analyze these raw 3D tomograms is not well-developed. This work focuses on a critical, yet often underappreciated, step of the analysis pipeline, that of 3D cell segmentation from the acquired tomograms. The current method employed for such tasks is the Otsu-based 3D watershed algorithm, which works well for isolated cells; however, it is very challenging to draw boundaries when the cells are clumped. This process is also memory intensive since the processing requires computation on a 3D stack of images. We report the CellSNAP (Cell Segmentation via Novel Algorithm for Phase Imaging) algorithm for the segmentation of QPI images, which outstrips the current gold standard in terms of speed, robustness, and implementation, achieving cell segmentation under 2 seconds per cell on a single-core processor. The implementation of CellSNAP can easily be parallelized on a multi-core system for further speed improvements. For the cases where segmentation is possible with the existing standard method, our algorithm displays an average difference of 5% for dry mass and 8% for volume measurements. We also show that CellSNAP can handle challenging image datasets where cells are clumped and marred by interferogram drifts, which pose major difficulties for all QPI-focused segmentation tools. We envision our work will lead to the broader adoption of QPI imaging for high-throughput analysis, which has, in part, been stymied by a lack of suitable image segmentation tools.

Trends and forecasted rates of adverse childhood experiences among adults in the United States: an analysis of the Behavioral Risk Factor Surveillance System.

CONTEXT: Many studies have shown increases in negative social aspects in the United States that may increase the likelihood of a child experiencing adversity. These rising trends include household dysfunction, poor mental health and substance use, crime rates, and incarceration. Additionally, the pathway of adverse childhood experiences (ACEs) may also perpetuate intergenerational trauma. OBJECTIVES: Given these increased trends, our objective was to determine the mean ACEs reported among adults by year of birth to assess trends of ACEs over time. METHODS: To assess ACEs trends in the United States, we utilized data from the 2020 Behavioral Risk Factor Surveillance System (BRFSS), a nationally representative survey. We summed individuals' reported ACEs and then calculated the mean ACE score within age cohorts (in 1-year increments) by year of birth. We utilized an auto-regressive integrated moving average (ARIMA) model to forecast mean ACEs through 2030. RESULTS: Respondents to the ACEs module (n=116,378) represented 63,076,717 adults in the United States, with an average age cohort of 1715 individuals. The mean reported ACEs among individuals 80 years or older (born in or before 1940) was 0.79, while the highest mean ACEs (2.74) were reported among the cohort born in 1998-an average increase of 0.022 ACEs per year. The ARIMA model forecasted that individuals born in 2018 will, on average, surpass a cumulative of three ACEs. CONCLUSIONS: Given the connection of ACEs to poor health outcomes and quality of life, this trend is alarming and provides evidence for the necessity of child maltreatment prevention. Multigenerational trauma-informed care and education are warranted for individuals with ACEs and may even prevent the cycle from recurring.

McGirt v Oklahoma and What Clinicians Should Know About Present-Day Child Abuse and Legacies of Forced Migration.

In 1997, Jimcy McGirt was convicted by the State of Oklahoma for sex crimes against a minor. McGirt appealed his conviction, citing that Oklahoma lacked jurisdiction over the case due to his tribal citizenship, since the crime took place on tribal territory. On July 9, 2020, the Supreme Court of the United States (SCOTUS) reversed the Oklahoma Court of Criminal Appeals' original decision for the case, citing that Congress had failed to disestablish reservations with regard to the Major Crimes Act, which gave the federal government jurisdiction over major felony crimes perpetrated by Native Americans on reservations.This ruling has already caused sweeping changes in the investigations and prosecutions of child maltreatment in eastern Oklahoma, as such cases may fall under the jurisdiction of federal agencies or tribal law enforcement. This article details the historic significance of the decision and the experiences of 3 child abuse pediatricians working as part of a multidisciplinary team while jurisdictional changes were implemented following the SCOTUS ruling.

Trends in public interest in child abuse in the United States: An infodemiology study of Google Trends from 2004 to 2022.

INTRODUCTION: More than 1 in 7 children in the United States experience abuse annually with rates remaining consistent over the past 2 decades. During this timeframe, several high-profile cases of child abuse and neglect were publicized in national media in addition to multiple investigations uncovering Indigenous children dying from abuse at Indian Boarding Schools. Increased media attention among other public health and medical topics has been linked to increased public interest, thus, our objective was to investigate trends in public interest from 2004 to 2022. METHODS: To assess trends in public interest, we extracted monthly relative search interest in child abuse from Google Trends. We constructed linear regression to determine the long-term trajectory of interest, and also compared the slope of the trend to other topics, such as domestic violence. Further, we compared mean relative search interest (RSI) from Child Abuse Awareness Month (April) to other months via t-test. Lastly, we assess by-state correlations of RSI and number of children abused. RESULTS: Since 2004, search interest in child abuse has significantly declined in the United States-more than other related search terms. Child Abuse Awareness Month showed spikes in RSI which were greater than other months. By-state correlations of RSI and abuse were moderate to weak. CONCLUSION: Despite heavy media attention covering stories of child abuse during the past 2 decades, search interest in child abuse has significantly declined. This trend may be related to aversion to secondary traumatic stress as news broadcasts often include stories of violence-of which child abuse stories may be most provoking. Following journalism guidance from the Centers for Disease Control and Prevention, reporting with focus on resiliency and prevention, rather than the individuals who perpetrated the crime, may provide more community support and increased public interest.

Asthma medications in schools: a cross-sectional analysis of the Asthma Call-back Survey 2017-2018.

CONTEXT: Asthma is the most common chronic disease affecting children in the United States. Goals for asthma management include symptom control, the ability to maintain a normal activity level, and minimizing adverse events. OBJECTIVES: The objective of this study is to analyze the number of children with asthma that are permitted to carry medications at school and without an asthma action plan. METHODS: In this study, we analyzed the Center for Disease Control and Prevention (CDC) Asthma Call-back Survey (ACBS) to assess the prevalence of children in school allowed to carry medication and with asthma action plans. Utilizing the sampling weights provided, we estimated population prevalence by age group and urbanicity. RESULTS: Results showed that, overall, 34.8% of students reported they were not allowed to carry asthma medications in school. Specifically, nearly 51% of children ages 5 to 9 and 33% of children ages 10 to 14 were reported not to be allowed to carry medications at school. Further, 58.2% of children did not have a written asthma action plan. Reported urbanicity was not significantly associated with access to medication at school (p=0.46) or having an asthma action plan (p=0.57). CONCLUSIONS: In our study, more than one-third of students were not permitted to carry asthma medications and nearly three-fifths did not have a written asthma action plan. Therefore, we recommend partnerships between schools, healthcare professionals, students, and osteopathic family physicians to increase access to asthma action plans and medication in schools.

Legal Outcomes of Suspected Maltreatment Cases Evaluated by a Child Abuse Pediatrician as Part of a Multidisciplinary Team Investigation.

Child abuse pediatricians often carry the stigma that their sole role is to diagnose maltreatment. In reality, child abuse pediatricians use their clinical experience and current evidence-based medicine to make the best medical diagnoses for the children they evaluate. To better understand the legal conclusion of suspected maltreatment cases with medical examinations, this study sought to: (i) evaluate the percentage of children seen for suspected maltreatment that led to a clinical diagnosis of maltreatment, (ii) determine the number and type of criminal charges associated, and (iii) analyze the legal outcomes of cases as they proceeded through the judicial system. This study retrospectively reviewed the legal outcomes of 1698 children medically evaluated in 2013-2014 as part of an investigation by a multidisciplinary team at a children's advocacy center in a mid-sized city in Oklahoma. Data were collected from electronic medical records, the district attorney's office, and a public court docket. Of the original cohort, 477 (28.09%) children yielded a medical diagnosis of at least one type of maltreatment. Further analysis yielded 115 unique court cases involving 138 defendants and 151 children. A total of 286 charges were filed resulting in 190 convictions. While maltreatment allegations yield a high number of children that must be evaluated, a comprehensive medical evaluation helps determine which cases do not have sufficient medical findings for a diagnosis of maltreatment. The findings in this study indicate that a majority of suspected maltreatment cases seen by child abuse pediatricians did not result in criminal court outcomes.

Prognostic Value of Doppler Ultrasound in Triplets Conceived by In Vitro Fertilization: A Case Report and Review of the Literature.

Umbilical artery Doppler ultrasound-which informs on maternal-fetal-placental blood flow-may be the most valuable surveillance tool in triplet pregnancies, crucial to diagnose early fetal growth restriction. To illustrate the prognostic value of Doppler ultrasound and launch a discussion of its role in multiple gestational, high-risk pregnancy, we present the case of a 42-year-old woman with trichorionic triamniotic triplet pregnancy conceived by in vitro fertilization, who showed early signs of poor outcome for one of the triplets via umbilical artery Doppler by the 23rd week and middle cerebral artery Doppler by the 29th week of gestation.