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Mohs Micrographic Surgery (MMS) for treatment of melanoma offers several advantages over wide local excision (WLE), including complete histologic margin evaluation, same-day resection and closure, and sparing of healthy tissue in critical anatomic sites. Recently, a large volume of clinical data demonstrating efficacy in MMS treatment of melanoma was published, leading to emerging patient safety considerations of incurred treatment costs, risk of tumor upstaging, and failure of care coordination for sentinel lymph node biopsy (SLNB). MMS offers a safe, effective, and value-based treatment for both melanoma in situ (MIS) and invasive melanoma (IM), particularly with immunohistochemistry use on frozen sections. Compared to wide local excision, MMS treatment demonstrates similar or improved outcomes for local tumor recurrence, melanoma-specific survival, and overall survival at long-term follow-up. Tumor upstaging risk is low, and if present, alteration to clinical management is minimal. Discussion of SLNB for eligible head and neck IM cases should be done prior to MMS. Though challenging, successful multidisciplinary coordination of SLNB with MMS has been demonstrated. Herein, we provide a detailed clinical review of evidence for MMS treatment of cutaneous melanoma and offer recommendations to address current controversies surrounding the evolving paradigm of surgical management for both MIS and invasive melanoma (IM)., Competing Interests: Conflicts of interest None disclosed, (Copyright © 2024 American Academy of Dermatology, Inc. All rights reserved.)

Competing Interests: The authors declare no conflicts of interest.

Competing Interests: The authors declare no conflicts of interest.

Melanoma's rare capacity to undergo heterologous differentiation can create significant diagnostic challenges. The molecular mechanisms underlying this phenomenon are not well understood. We present an unusual case of subungual melanoma exhibiting extensive cartilaginous differentiation and provide insights into its molecular and cytogenomic features. Histopathologically, the tumor was predominantly composed of nodules of malignant cartilage in association with a smaller population of nested epithelioid to rhabdoid cells. Immunohistochemically, the tumor cells in both components were positive for S100, SOX10, and PRAME, and were negative for Melan-A and HMB-45. Molecular analysis by whole exome DNA sequence did not detect any pathogenic variants in genes commonly implicated in melanoma. Additional analysis by SNP chromosomal microarray revealed a complex genome characterized by numerous chromosomal losses and gains, including a homozygous deletion of the CDKN2A locus and a heterozygous deletion of the locus containing EXT2, a tumor suppressor implicated in hereditary multiple osteochondromas and secondary chondrosarcomas. This case underscores the importance of recognizing cartilaginous differentiation as a rare manifestation of melanoma, particularly at subungual sites, and suggests that at least some of these melanomas may be driven by non-canonical molecular pathways., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Racial and ethnic disparities are evident in the accessibility of treatment for opioid use disorder (OUD). Even when medications for OUD (MOUD) are accessible, racially and ethnically minoritized groups have higher attrition rates from treatment. Existing literature has primarily identified the specific racial and ethnic groups affected by these disparities, but has not thoroughly examined interventions to address this gap. Recovery peer navigators (RPNs) have been shown to improve access and overall retention on MOUD., Patients and Methods: In this retrospective cohort study, we evaluate the role of RPNs on patient retention in clinical care at an outpatient program in a racially and ethnically diverse urban community. Charts were reviewed of new patients seen from January 1, 2019 through December 31, 2019. Sociodemographic and clinical visit data, including which providers and services were utilized, were collected, and the primary outcome of interest was continuous retention in care. Bivariate analysis was done to test for statistically significant associations between variables by racial/ethnic group and continuous retention in care using Student's t-test or Pearson's chi-square test. Variables with p value ≤0.10 were included in a multivariable regression model., Results: A total of 131 new patients were included in the study. RPNs improved continuous retention in all-group analysis (27.6% pre-RPN compared to 80.2% post-RPN). Improvements in continuous retention were observed in all racial/ethnic subgroups but were statistically significant in the non-Hispanic Black (NHB) group ( p  < 0.001). Among NHB, increases in continuous retention were observed post-RPN in patients with male sex ( p  < 0.001), public health insurance ( p  < 0.001), additional substance use ( p  < 0.001), medical comorbidities ( p  < 0.001), psychiatric comorbidities ( p  = 0.001), and unstable housing ( p  = 0.005). Multivariate logistic regression demonstrated that patients who lacked insurance had lower odds of continuous retention compared to patients with public insurance (aOR = 0.17, 95% CI 0.039-0.70, p  = 0.015)., Conclusions: RPNs can improve clinical retention for patients with OUD, particularly for individuals experiencing several sociodemographic and clinical factors that are typically correlated with discontinuation of care.

Introduction: The development of paediatric medical devices continues to lag adult medical devices and contributes to issues of inequity, safety, quality and patient outcomes. New legislation and funding mechanisms have been introduced over the past two decades, but the gap remains. Clinical trials have been identified as a pain point, but components of effective clinical research infrastructure are poorly understood. As part of a multimodal research strategy, the Pediatric Device Consortia (PDC) will conduct a scoping review to better understand infrastructural barriers to and facilitators of paediatric medical device clinical research identified in the health sciences literature., Methods and Analysis: The following databases will be included for this review: Medline, Embase, Cochrane CENTRAL, Web of Science and IEEE Xplore. Additional grey literature will be sought out through Google Scholar and reviewing the citations of included studies. Included studies will discuss medical devices according to the U.S. Food and Drug Administration classification, focus on the paediatric population (ages 0-21 years) and involve human premarket or postmarket research. All study types that were published in 2007-present in English, Spanish, French or Italian will be included. Using Covidence web-based software, two independent reviewers will screen the resulting titles, abstracts and the full text of potential studies. Conflicts will be resolved by the primary investigator during both phases. REDCap will be used for quantitative and qualitative data charting, generating data tables and narrative synthesis., Ethics and Dissemination: This research did not require research ethics board consideration as it does not involve human participants and all data will be collected from published literature. We will share our findings through peer-reviewed manuscripts, clinical and research conference presentations and professional networks available to the PDC., Study Registration: Open Science Framework (https://osf.io/k72bn)., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Germline pathogenic variants (PVs) in the BRCA1 and BRCA2 genes confer elevated risks of breast, ovarian, and other cancers. Lynch syndrome (LS) is associated with increased risks of multiple cancer types including colorectal and uterine cancers. Current cancer risk mitigation strategies have focused on pharmacologic risk reduction, enhanced surveillance, and preventive surgeries. While these approaches can be effective, they stand to be improved on because of either limited efficacy or undesirable impact on quality of life. The current review summarizes ongoing investigational efforts in cancer risk prevention strategies for patients with germline PVs in BRCA1 , BRCA2 , or LS-associated genes. These efforts span radiation, surgery, and pharmacology including vaccine strategies. Understanding the molecular events involved in the premalignant to malignant transformation in high-risk individuals may ultimately contribute significantly to novel prevention strategies.

Competing Interests: Competing interests: None declared.

Background: Germline heterozygous TP53 pathogenic variants (PVs) cause Li Fraumeni Syndrome (LFS, OMIM#151623). TP53 PVs at lower-than-expected variant allele frequencies (VAF) may reflect postzygotic mosaicism (PZM) or clonal hematopoiesis (CH); however, no guidelines exist for workup and clinical management., Patients and Methods: Retrospective analysis of probands who presented to an academic cancer genetics program with a TP53 PV result on germline genetic testing., Results: Twenty-one of 125 unrelated probands (17 %) were found to harbor a TP53 PV with VAF<30 % or a designation of "mosaic". A diagnosis of PZM was made in nine (43 %) due to a clinical phenotype consistent with LFS with (n = 8) or without (n = 1) positive ancillary tissue testing. Twelve patients (57 %) were diagnosed with presumed CH (pCH) due to a diagnosis of a myeloproliferative neoplasm, negative ancillary tissue testing, clinical phenotype not meeting LFS criteria, no cancer, and/or no first cancer age<50. Of the 19 patients with biological offspring, nine had either partial or complete offspring testing, all negative., Conclusions: Determining the etiology of low VAF TP53 PVs requires ancillary tissue testing and incorporation of clinical phenotype. Discerning PZM versus CH is important to provide optimal care and follow-up., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Combinations of immune checkpoint inhibitors (ICI, including anti-PD-1/PD-L1) and chemotherapy have been FDA approved for metastatic and early-stage triple-negative breast cancer (TNBC), but most patients do not benefit. B7-H4 is a B7 family ligand with proposed immunosuppressive functions being explored as a cancer immunotherapy target and may be associated with anti-PD-L1 resistance. However, little is known about its regulation and effect on immune cell function in breast cancers. We assessed murine and human breast cancer cells to identify regulation mechanisms of B7-H4 in vitro. We used an immunocompetent anti-PD-L1-sensitive orthotopic mammary cancer model and induced ectopic expression of B7-H4. We assessed therapy response and transcriptional changes at baseline and under treatment with anti-PD-L1. We observed B7-H4 was highly associated with epithelial cell status and transcription factors and found to be regulated by PI3K activity. EMT6 tumors with cell-surface B7-H4 expression were more resistant to immunotherapy. In addition, tumor-infiltrating immune cells had reduced immune activation signaling based on transcriptomic analysis. Paradoxically, in human breast cancer, B7-H4 expression was associated with survival benefit for patients with metastatic TNBC treated with carboplatin plus anti-PD-L1 and was associated with no change in response or survival for patients with early breast cancer receiving chemotherapy plus anti-PD-1. While B7-H4 induces tumor resistance to anti-PD-L1 in murine models, there are alternative mechanisms of signaling and function in human cancers. In addition, the strong correlation of B7-H4 to epithelial cell markers suggests a potential regulatory mechanism of B7-H4 independent of PD-L1., Significance: This translational study confirms the association of B7-H4 expression with a cold immune microenvironment in breast cancer and offers preclinical studies demonstrating a potential role for B7-H4 in suppressing response to checkpoint therapy. However, analysis of two clinical trials with checkpoint inhibitors in the early and metastatic settings argue against B7-H4 as being a mechanism of clinical resistance to checkpoints, with clear implications for its candidacy as a therapeutic target., (© 2024 The Authors; Published by the American Association for Cancer Research.)

Competing Interests: We all contributed to the Criminalized Care: How Louisiana's Abortion Bans Endanger Patients and Clinicians(7) report and MH and PKS contributed to In Clinicians' Own Words: How Abortion Bans Impede Emergency Medical Treatment for Pregnant Patients in Idaho(10) brief. We declare no other competing interests.

Purpose: The purpose of this study was to assess the current use and reliability of artificial intelligence (AI)-based algorithms for analyzing cataract surgery videos., Methods: A systematic review of the literature about intra-operative analysis of cataract surgery videos with machine learning techniques was performed. Cataract diagnosis and detection algorithms were excluded. Resulting algorithms were compared, descriptively analyzed, and metrics summarized or visually reported. The reproducibility and reliability of the methods and results were assessed using a modified version of the Medical Image Computing and Computer-Assisted (MICCAI) checklist., Results: Thirty-eight of the 550 screened studies were included, 20 addressed the challenge of instrument detection or tracking, 9 focused on phase discrimination, and 8 predicted skill and complications. Instrument detection achieves an area under the receiver operator characteristic curve (ROC AUC) between 0.976 and 0.998, instrument tracking an mAP between 0.685 and 0.929, phase recognition an ROC AUC between 0.773 and 0.990, and complications or surgical skill performs with an ROC AUC between 0.570 and 0.970., Conclusions: The studies showed a wide variation in quality and pose a challenge regarding replication due to a small number of public datasets (none for manual small incision cataract surgery) and seldom published source code. There is no standard for reported outcome metrics and validation of the models on external datasets is rare making comparisons difficult. The data suggests that tracking of instruments and phase detection work well but surgical skill and complication recognition remains a challenge for deep learning., Translational Relevance: This overview of cataract surgery analysis with AI models provides translational value for improving training of the clinician by identifying successes and challenges.

Germline genetic evaluation is indicated for all patients with epithelial ovarian cancer (EOC). For testing to have clinical utility, results must be documented within the electronic medical record (EMR) and accessible to providers at the point of care, which can be challenging in the context of current EMR limitations and genetic testing processes. We examined the receipt of genetics services and EMR capture of genetic testing results in patients with EOC. We conducted a retrospective chart review to examine germline genetic evaluations among patients with EOC seen by a gynecologic or medical oncologist at the University of Pennsylvania in 2016. EMRs were reviewed to determine: (1) if patients were referred for genetic evaluation; (2) if genetic testing was performed; (3) if results were documented in office notes, scanned third-party test reports, and/or the EMR problem list; (4) if provider notes correctly listed the variant classification. Overall, 413 (62%) of patients had documented genetic testing. Genetic testing was documented in almost all provider notes (96%) and the majority of scanned EMR reports (64%). Pathogenic variants were found in 119 (29%) individuals; the majority (70%) had genetic testing documented within EMR problem lists. Provider notes were highly accurate in describing variant classification. In this study, genetic testing was performed and documented in the EMR for most EOC patients. Approximately one-third of those tested did not have scanned test reports specifying variant found, limiting the utility of test results for cascade testing and therapeutic decisions., (© 2023 National Society of Genetic Counselors.)

Purpose: To develop recommendations for germline mutation testing for patients with breast cancer., Methods: An ASCO-Society of Surgical Oncology (SSO) panel convened to develop recommendations based on a systematic review and formal consensus process., Results: Forty-seven articles met eligibility criteria for the germline mutation testing recommendations; 18 for the genetic counseling recommendations., Recommendations: BRCA1 / 2 mutation testing should be offered to all newly diagnosed patients with breast cancer ≤65 years and select patients >65 years based on personal history, family history, ancestry, or eligibility for poly(ADP-ribose) polymerase (PARP) inhibitor therapy. All patients with recurrent breast cancer who are candidates for PARP inhibitor therapy should be offered BRCA1 / 2 testing, regardless of family history. BRCA1 / 2 testing should be offered to women who develop a second primary cancer in the ipsilateral or contralateral breast. For patients with prior history of breast cancer and without active disease, testing should be offered to patients diagnosed ≤65 years and selectively in patients diagnosed after 65 years, if it will inform personal and family risk. Testing for high-penetrance cancer susceptibility genes beyond BRCA1 / 2 should be offered to those with supportive family histories; testing for moderate-penetrance genes may be offered if necessary to inform personal and family cancer risk. Patients should be provided enough pretest information for informed consent; those with pathogenic variants should receive individualized post-test counseling. Variants of uncertain significance should not impact management, and patients with such variants should be followed for reclassification. Referral to providers experienced in clinical cancer genetics may help facilitate patient selection and interpretation of expanded testing, and provide counseling of individuals without pathogenic germline variants but with significant family history.Additional information is available at www.asco.org/breast-cancer-guidelines.

Despite the success of immune checkpoint inhibition (ICI) in treating cancer, patients with triple-negative breast cancer (TNBC) often develop resistance to therapy, and the underlying mechanisms are unclear. MHC-I expression is essential for antigen presentation and T-cell-directed immunotherapy responses. This study demonstrates that TNBC patients display intratumor heterogeneity in regional MHC-I expression. In murine models, loss of MHC-I negates antitumor immunity and ICI response, whereas intratumor MHC-I heterogeneity leads to increased infiltration of natural killer (NK) cells in an IFNγ-dependent manner. Using spatial technologies, MHC-I heterogeneity is associated with clinical resistance to anti-programmed death (PD) L1 therapy and increased NK:T-cell ratios in human breast tumors. MHC-I heterogeneous tumors require NKG2A to suppress NK-cell function. Combining anti-NKG2A and anti-PD-L1 therapies restores complete response in heterogeneous MHC-I murine models, dependent on the presence of activated, tumor-infiltrating NK and CD8+ T cells. These results suggest that similar strategies may enhance patient benefit in clinical trials., Significance: Clinical resistance to immunotherapy is common in breast cancer, and many patients will likely require combination therapy to maximize immunotherapeutic benefit. This study demonstrates that heterogeneous MHC-I expression drives resistance to anti-PD-L1 therapy and exposes NKG2A on NK cells as a target to overcome resistance. This article is featured in Selected Articles from This Issue, p. 201., (©2023 The Authors; Published by the American Association for Cancer Research.)

Importance: Agents targeting programmed death ligand 1 (PD-L1) have demonstrated efficacy in triple-negative breast cancer (TNBC) when combined with chemotherapy and are now the standard of care in patients with PD-L1-positive metastatic disease. In contrast to microtubule-targeting agents, the effect of combining platinum compounds with programmed cell death 1 (PD-1)/PD-L1 immunotherapy has not been extensively determined., Objective: To evaluate the efficacy of atezolizumab with carboplatin in patients with metastatic TNBC., Design, Setting, and Participants: This phase 2 randomized clinical trial was conducted in 6 centers from August 2017 to June 2021., Interventions: Patients with metastatic TNBC were randomized to receive carboplatin area under the curve (AUC) 6 alone or with atezolizumab, 1200 mg, every 3 weeks until disease progression or unacceptable toxic effects with a 3-year duration of follow-up., Main Outcome and Measures: The primary end point was investigator-assessed progression-free survival (PFS). Secondary end points included overall response rate (ORR), clinical benefit rate (CBR), and overall survival (OS). Other objectives included correlation of response with tumor PD-L1 levels, tumor-infiltrating lymphocytes (TILs), tumor DNA- and RNA-sequenced biomarkers, TNBC subtyping, and multiplex analyses of immune markers., Results: All 106 patients with metastatic TNBC who were enrolled were female with a mean (range) age of 55 (27-79) years, of which 12 (19%) identified as African American/Black, 1 (1%) as Asian, 73 (69%) as White, and 11 (10%) as unknown. Patients were randomized and received either carboplatin (n = 50) or carboplatin and atezolizumab (n = 56). The combination improved PFS (hazard ratio [HR], 0.66; 95% CI, 0.44-1.01; P = .05) from a median of 2.2 to 4.1 months, increased ORR from 8.0% (95% CI, 3.2%-18.8%) to 30.4% (95% CI, 19.9%-43.3%), increased CBR at 6 months from 18.0% (95% CI, 9.8%-30.1%) to 37.5% (95% CI, 26.0%-50.6%), and improved OS (HR, 0.60; 95% CI, 0.37-0.96; P = .03) from a median of 8.6 to 12.6 months. Subgroup analysis showed PD-L1-positive tumors did not benefit more from adding atezolizumab (HR, 0.62; 95% CI, 0.23-1.65; P = .35). Patients with high TILs (HR, 0.12; 95% CI, 0.30-0.50), high mutation burden (HR, 0.50; 95% CI, 0.23-1.06), and prior chemotherapy (HR, 0.59; 95% CI, 0.36-0.95) received greater benefit on the combination. Patients with obesity and patients with more than 125 mg/dL on-treatment blood glucose levels were associated with better PFS (HR, 0.35; 95% CI, 0.10-1.80) on the combination. TNBC subtypes benefited from adding atezolizumab, except the luminal androgen receptor subtype., Conclusions and Relevance: In this randomized clinical trial, the addition of atezolizumab to carboplatin significantly improved survival of patients with metastatic TNBC regardless of PD-L1 status. Further, lower risk of disease progression was associated with increased TILs, higher mutation burden, obesity, and uncontrolled blood glucose levels., Trial Registration: ClinicalTrials.gov Identifier: NCT03206203.

Background: The burden of pulmonary disease in children with CHD remains under-recognised. Studies have examined children with single ventricle and two ventricle heart disease and documented a decreased forced vital capacity. Our study sought to further explore the pulmonary function of children with CHD., Methods: A retrospective review was performed of spirometry in CHD patients over a 3-year period. Spirometry data were corrected for size, age, and gender and analysed using z-scores., Results: The spirometry of 260 patients was analysed. About 31% had single ventricle (n = 80, 13.6 years (interquartile range 11.5-16.8)) and 69% had two ventricle circulation (n = 180, 14.4 years (interquartile range 12.0-17.3)). Single ventricle patients were found to have a lower median forced vital capacity z-score compared to two ventricle patients (p = 0.0133). The prevalence of an abnormal forced vital capacity was 41% in single ventricle patients and 29% in two ventricle patients. Two ventricle patients with tetralogy of Fallot and truncus arteriosus had similar low forced vital capacity comparable to single ventricle patients. The number of cardiac surgeries predicted an abnormal forced vital capacity in two ventricle patients except tetralogy of Fallot patients., Conclusion: Pulmonary morbidity in patients with CHD is common with a decreased forced vital capacity noted in single ventricle and two ventricle patients. Forced vital capacity is lower in patients with single ventricle circulation; however, two ventricle patients with tetralogy of Fallot or truncus arteriosus have similar lung function in comparison to the single ventricle group. The number of surgical interventions was predictive of forced vital capacity z-score in some but not all two ventricle patients and not predictive in single ventricle patients suggesting a multifactorial to pulmonary disease in children with CHD.

Nonmedical descriptors, adjectives that are not related to a medical condition, such as "cute," are often used in presentations in pediatrics. We hypothesize that patterns of their use may reflect obesity bias. Descriptors used by pediatric residents presenting cases of children <9 years in an outpatient clinic during the 2018-2019 and 2019-2020 academic years were recorded. The primary outcome was the association of the use of positive nonmedical descriptors with children's obesity status using logistic regression. Positive descriptors were used in 14% of 994 presentations. Most addressed the appearance of the child with variations of "cute" and "adorable." There was no variation in use of positive descriptors by obesity status. On multivariate logistic regression, the odds of using positive descriptors were higher among female residents, and positive descriptor use declined with patient age. Negative descriptors were rare and often focused on weight.

Purpose: We developed a web-based education intervention as an alternative to predisclosure education with a genetic counselor (GC) to reduce participant burden and provider costs with return of genetic research results., Methods: Women at three sites who participated in 11 gene discovery research studies were contacted to consider receiving cancer genetic research results. Participants could complete predisclosure education through web education or with a GC. Outcomes included uptake of research results, factors associated with uptake, and patient-reported outcomes., Results: Of 819 participants, 178 actively (21.7%) and 167 passively (20.4%) declined return of results; 474 (57.9%) were enrolled. Most (60.3%) received results although this was lower than the 70% uptake we hypothesized. Passive and active decliners were more likely to be Black, to have less education, and to have not received phone follow-up after the invitation letter. Most participants selected web education (88.5%) as an alternative to speaking with a GC, but some did not complete or receive results. Knowledge increased significantly from baseline to other time points with no significant differences between those who received web versus GC education. There were no significant increases in distress between web and GC education., Conclusion: Interest in web-based predisclosure education for return of genetic research results was high although it did not increase uptake of results. We found no negative patient-reported outcomes with web education, suggesting that it is a viable alternative delivery model for reducing burdens and costs of returning genetic research results. Attention to attrition and lower uptake of results among Black participants and those with less formal education are important areas for future research.

Significance: Sickle cell disease (SCD), characterized by painful vaso-occlusive crises, is associated with cognitive decline. However, objective quantification of cognitive decline in SCD remains a challenge, and the associated hemodynamics are unknown., Aim: To address this, we utilized functional near-infrared spectroscopy (fNIRS) to measure prefrontal cortex (PFC) oxygenation responses to N -back working memory tasks in SCD patients and compared them with healthy controls., Approach: We quantified the PFC oxygenation rate as an index of cognitive activity in each group and compared them. In half of the participants, a Stroop test was administered before they started N -back to elevate their baseline stress level., Results: In SCD compared to healthy controls, we found that (1) under a high baseline stress level, there were significantly greater oxygenation responses during the 2-back task, further elevated with histories of stroke; (2) there was a marginally slower N -back response time, and it was even slower with a history of stroke; and (3) the task accuracy was not different., Conclusions: Additional requirements for processing time, PFC resources, and PFC oxygenation in SCD patients offer an important basis for understanding their cognitive decline and highlight the potential of fNIRS for evaluating cognitive functions., (© 2023 The Authors.)

Introduction: The incidence of post vitrectomy endophthalmitis (PVE) is reported to be between 0.02 and 0.84%. Resterilization of single use instruments is a common practice amidst developing countries to make it more affordable to the patients by reducing the cost of the surgery and also reduce the environmental hazard. The aim of our study is to evaluate the incidence of PVE amidst existing sterilization practices of reused instruments in multiple vitreoretinal centres in India., Methodology: Centres with an endophthalmitis tracking system were invited to participate in a survey. Twenty-five centres were sent a questionnaire via email. The questionnaire included details about the institution, number of vitrectomies performed in a year, sterilization practices followed pre-operatively, intraoperatively and postoperatively, incidence of endophthalmitis and instrument reuse policies., Results: A total of 29 cases of endophthalmitis were reported out of the 47,612 vitrectomies performed across various centres. The mean incidence of endophthalmitis was 0.06%. There was no difference in the rates of endophthalmitis based on various pre-operative, intraoperative or postoperative prophylactic measures. Nearly 80% of the centres change most of the instruments after every case, while the rest reused. The mean number of times a cutter was being reused until discarded was 4.7. Nearly 76% followed a performance-based protocol, and the remaining 24% had a fixed protocol for the number of times an instrument can be reused before discarding it., Conclusion: PVE rates are not significantly different in India despite the multiuse of single use instruments. The purpose of this paper is not to suggest an alternate protocol but to creating one in the future with these results in mind, to rationalise the use of single use instruments, make VR surgery more affordable and also have a positive impact on the carbon footprint of consumables in surgery., (© 2023. The Author(s), under exclusive licence to The Royal College of Ophthalmologists.)

Background: The pediatric medical device development (PMDD) process is highly complex, beset by a variety of financial, technical, medical, and regulatory barriers. Startup company innovators and academic investigators often struggle with accessing specialized knowledge relating to regulatory requirements, product development, research, and marketing strategies., Objectives: The West Coast Consortium for Technology & Innovation in Pediatrics (CTIP) conducted an educational needs assessment to understand knowledge gaps and inform our educational strategy., Methods: We surveyed a total of 49 medical device startups and 52 academic investigators. Electronic surveys were developed for each group on Qualtrics and focused on manufacturing, regulatory, research, commercialization, and funding. Descriptive statistics were used., Results: A larger proportion of academic investigator respondents had a clinical background compared to the startup respondents (45% vs. 22%). The biggest barriers for academic investigators were understanding regulatory and safety requirements testing (52%) and finding and obtaining non-dilutive funding was the most difficult (54%). Among startups, understanding clinical research methods and requirements was the biggest barrier (79%)., Conclusion: Startup companies and academic investigators have similar, but not identical, educational needs to better understand the PMD development process. Investigators need more support in identifying funding sources, while startup companies identified an increased need for education on research regulatory topics. These findings can help guide curriculum development as well as opportunities for partnerships between academia and startups., Competing Interests: None., (© The Author(s) 2023.)

Competing Interests: We all contributed to the PHR analysis, Broken Promises,(7) that is discussed in this Comment. The initial development of this research project was supported through an organisational grant to Physicians for Human Rights, the donor for this grant must remain unnamed at the time of publication. We declare no other competing interests.

Objective: Patient-reported outcome measures (PROMs) are critical to drive patient-centered care and to understanding patients' perspectives on their health status, quality of life, and the overall effectiveness of the care they receive. PROMs are increasingly being used in clinical and research settings, but the mechanisms to aggregate data from different systems can be cumbersome., Materials and Methods: As part of an FDA Real-World Evidence demonstration project, we enriched routine care clinical data from our Cerner electronic health record (EHR) with PROMs collected using REDCap. We used SSIS, sFTP, and the REDCap Application Programming Interface to aggregate both data sources into the Cerner HealtheIntent Population Health Platform., Results: We successfully built dashboards, reports, and datasets containing both REDCap and EHR data collected prospectively., Discussion: This technically straightforward approach using commonly available clinical and research tools can be readily adopted and adapted by others to better integrate PROMs with clinical data sources., Competing Interests: None declared., (© The Author(s) 2023. Published by Oxford University Press on behalf of the American Medical Informatics Association.)

Purpose: Addition of ataxia telangiectasia and Rad3-related kinase inhibitors (ATRi) to PARP inhibitors (PARPi) overcomes PARPi resistance in high-grade serous ovarian cancer (HGSOC) cell and mouse models. We present the results of an investigator-initiated study of combination PARPi (olaparib) and ATRi (ceralasertib) in patients with acquired PARPi-resistant HGSOC., Patients and Methods: Eligible patients had recurrent, platinum-sensitive BRCA1/2 mutated or homologous recombination (HR)-deficient (HRD) HGSOC and clinically benefited from PARPi (response by imaging/CA-125 or duration of maintenance therapy; > 12 months first-line or > 6 months ≥ second-line) before progression. No intervening chemotherapy was permitted. Patients received olaparib 300 mg twice daily and ceralasertib 160 mg daily on days 1 to 7 of a 28-day cycle. Primary objectives were safety and objective response rate (ORR)., Results: Thirteen patients enrolled were evaluable for safety and 12 for efficacy; 62% (n = 8) had germline BRCA1/2 mutations, 23% (n = 3) somatic BRCA1/2 mutations, and 15% (n = 2) tumors with positive HRD assay. Prior PARPi indication was treatment for recurrence (54%, n = 7), second-line maintenance (38%, n = 5) and first-line treatment with carboplatin/paclitaxel (8%, n = 1). There were 6 partial responses yielding an ORR of 50% (95% confidence interval, 0.15-0.72). Median treatment duration was 8 cycles (range 4-23+). Grade (G) 3/4 toxicities were 38% (n = 5); 15% (n = 2) G3 anemia, 23% (n = 3) G3 thrombocytopenia, 8% (n = 1) G4 neutropenia. Four patients required dose reductions. No patient discontinued treatment due to toxicity., Conclusions: Combination olaparib and ceralasertib is tolerable and shows activity in HR-deficient platinum-sensitive recurrent HGSOC that benefited and then progressed with PARPi as the penultimate regimen. These data suggest that ceralasertib resensitizes PARPi-resistant HGSOCs to olaparib, warranting further investigation., (©2023 American Association for Cancer Research.)

Purpose: To assess inter-rater reliability in the detection of proliferative diabetic retinopathy (PDR) changes using wide-field optical coherence tomography angiography (WF-OCTA) versus fluorescein angiography (FA)., Methods: This retrospective, cross-sectional study included patients with severe nonproliferative and PDR. Images were acquired with 12 × 12 mm WF-OCTA and FA with a 55° lens. Images were cropped to represent the exact same field of view. Qualitative (detection of neovascularization at the disc [NVD] and elsewhere [NVE], enlarged foveal avascular zone [FAZ], vitreous hemorrhage [VH]) and quantitative analyses (FAZ area, horizontal, vertical, and maximum FAZ diameter) were performed by 2 masked graders using ImageJ. Inter-rater reliability was calculated using unweighted Cohen's kappa coefficient (κ) for qualitative analyses and intraclass correlation coefficients (ICC) for quantitative analyses., Results: Twenty-three eyes of 17 patients were included. Inter-rater reliability was higher for FA than for WF-OCTA in qualitative analyses: κ values were 0.65 and 0.78 for detection of extended FAZ, 0.83 and 1.0 for NVD, 0.78 and 1.0 for NVE, and 0.19 and 1 for VH for WF-OCTA and FA, respectively. In contrast, inter-rater reliability was higher for WF-OCTA than for FA in the quantitative analyses: ICC values were 0.94 and 0.76 for FAZ size, 0.92 and 0.79 for horizontal FAZ diameter, 0.82 and 0.72 for vertical FAZ diameter, and 0.88 and 0.82 for maximum FAZ diameter on WF-OCTA and FA, respectively., Conclusions: Inter-rater reliability of FA is superior to WF-OCTA for qualitative analyses whereas inter-rater reliability of WF-OCTA is superior to FA for quantitative analyses., Translational Relevance: The study highlights the specific merits of both imaging modalities in terms of reliability. FA should be preferred for qualitative parameters, whereas WF-OCTA should be preferred for quantitative parameters.

In April 2023, the World Health Organization (WHO) issued new estimates affirming that one in six individuals experience infertility globally. Yet, many states are unclear on their responsibility to prevent infertility, ensure access to treatment, and to end the harm suffered by individuals who are considered infertile. Responding to this uncertainty, in June 2023, the United Nations Office of the High Commissioner on Human Rights (OHCHR) issued a new research paper explaining states' legal obligations regarding infertility. Importantly, OHCHR underscores that states must take steps to prevent infertility by addressing its root causes and ensure access to treatment. Further, states must address the negative consequences of infertility, including stigma and violence, as well as the discriminatory stereotypes that lead to certain groups facing disproportionate harm from infertility. This article provides an overview of the OHCHR report and explains what this means for healthcare providers, who have a critical role to play in providing care and advocating for legal and policy reform necessary to prevent, diagnose, and treat infertility., (© 2023 International Federation of Gynecology and Obstetrics.)

Purpose: Journals are increasingly using social media to increase article engagement. We aim to determine the impact of Instagram promotion on, and identify social media tools that effectively enhance, plastic surgery article engagement and impact., Methods: Instagram accounts for Plastic and Reconstructive Surgery , Annals of Plastic Surgery , Aesthetic Surgery Journal , and Aesthetic Plastic Surgery were reviewed for posts published by February 8, 2022. Open access journal articles were excluded. Post caption word count and number of likes, tagged accounts, and hashtags were recorded. Inclusion of videos, article links, or author introductions was noted. All articles from journal issues published between the dates of the first and last posts promoting articles were reviewed. Altmetric data approximated article engagement. Citation numbers from the National Institutes of Health iCite tool approximated impact. Differences in engagement and impact of articles with and without Instagram promotion were compared by Mann-Whitney U tests. Univariate and multivariable regressions identified factors predictive of more engagement (Altmetric Attention Score, ≥5) and citations (≥7)., Results: A total of 5037 articles were included, with 675 (13.4%) promoted on Instagram. Of posts featuring articles, 274 (40.6%) included videos, 469 (69.5%) included article links, and 123 included (18.2%) author introductions. Promoted articles had higher median Altmetric Attention Scores and citations ( P < 0.001). On multivariable analysis, using more hashtags predicted higher article Altmetric Attention Scores (odds ratio [OR], 1.85; P = 0.002) and more citations (OR, 1.90; P < 0.001). Including article links (OR, 3.52; P < 0.001) and tagging more accounts (OR, 1.64; P = 0.022) predicted higher Altmetric Attention Scores. Including author introductions negatively predicted Altmetric Attention Scores (OR, 0.46; P < 0.001) and citations (OR, 0.65; P = 0.047). Caption word count had no significant impact on article engagement or impact., Conclusions: Instagram promotion increases plastic surgery article engagement and impact. Journals should use more hashtags, tag more accounts, and include manuscript links to increase article metrics. We recommend that authors promote on journal social media to maximize article reach, engagement, and citations, which positively impacts research productivity with minimal additional effort in designing Instagram content., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: Treatments are limited for metastatic melanoma and metastatic triple-negative breast cancer (mTNBC). This pilot phase I trial (NCT03060356) examined the safety and feasibility of intravenous RNA-electroporated chimeric antigen receptor (CAR) T cells targeting the cell-surface antigen cMET., Experimental Design: Metastatic melanoma or mTNBC subjects had at least 30% tumor expression of cMET, measurable disease and progression on prior therapy. Patients received up to six infusions (1 × 10e8 T cells/dose) of CAR T cells without lymphodepleting chemotherapy. Forty-eight percent of prescreened subjects met the cMET expression threshold. Seven (3 metastatic melanoma, 4 mTNBC) were treated., Results: Mean age was 50 years (35-64); median Eastern Cooperative Oncology Group 0 (0-1); median prior lines of chemotherapy/immunotherapy were 4/0 for TNBC and 1/3 for melanoma subjects. Six patients experienced grade 1 or 2 toxicity. Toxicities in at least 1 patient included anemia, fatigue, and malaise. One subject had grade 1 cytokine release syndrome. No grade 3 or higher toxicity, neurotoxicity, or treatment discontinuation occurred. Best response was stable disease in 4 and disease progression in 3 subjects. mRNA signals corresponding to CAR T cells were detected by RT-PCR in all patients' blood including in 3 subjects on day +1 (no infusion administered on this day). Five subjects underwent postinfusion biopsy with no CAR T-cell signals seen in tumor. Three subjects had paired tumor tissue; IHC showed increases in CD8 and CD3 and decreases in pS6 and Ki67., Conclusions: Intravenous administration of RNA-electroporated cMET-directed CAR T cells is safe and feasible., Significance: Data evaluating CAR T therapy in patients with solid tumors are limited. This pilot clinical trial demonstrates that intravenous cMET-directed CAR T-cell therapy is safe and feasible in patients with metastatic melanoma and metastatic breast cancer, supporting the continued evaluation of cellular therapy for patients with these malignancies., (© 2023 The Authors; Published by the American Association for Cancer Research.)

The analytical validation is reported for a targeted methylation-based cell-free DNA multi-cancer early detection test designed to detect cancer and predict the cancer signal origin (tissue of origin). A machine-learning classifier was used to analyze the methylation patterns of >105 genomic targets covering >1 million methylation sites. Analytical sensitivity (limit of detection [95% probability]) was characterized with respect to tumor content by expected variant allele frequency and was determined to be 0.07%-0.17% across five tumor cases and 0.51% for the lymphoid neoplasm case. Test specificity was 99.3% (95% confidence interval, 98.6-99.7%). In the reproducibility and repeatability study, results were consistent in 31/34 (91.2%) pairs with cancer and 17/17 (100%) pairs without cancer; between runs, results were concordant for 129/133 (97.0%) cancer and 37/37 (100%) non-cancer sample pairs. Across 3- to 100-ng input levels of cell-free DNA, cancer was detected in 157/182 (86.3%) cancer samples but not in any of the 62 non-cancer samples. In input titration tests, cancer signal origin was correctly predicted in all tumor samples detected as cancer. No cross-contamination events were observed. No potential interferent (hemoglobin, bilirubin, triglycerides, genomic DNA) affected performance. The results of this analytical validation study support continued clinical development of a targeted methylation cell-free DNA multi-cancer early detection test., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: GA, WL, FEO, MR, PS, JRB, LE, GN, AM, PWM and NH are former employees of GRAIL, LLC and may have equity in the company. MHM is a consultant to Delfi Diagnostics and to Fellow Health and a former employee of GRAIL, LLC, with equity in all three companies. AMA is an advisor to Foresite Labs, San Francisco, California and Boston, Massachusetts, and a former employee of GRAIL, LLC, and holds equity in both companies. All other authors are employees of GRAIL, LLC, with equity in the company. GRAIL, LLC is a subsidiary of Illumina, Inc. currently held separate from Illumina Inc. under the terms of the Interim Measures Order of the European Commission dated 29 October 2021., (Copyright: © 2023 Alexander 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.)

Introduction: Cyclin-dependent-kinase 4/6(CDK4/6) inhibitors are widely used as a first-line systemic treatment for patients with hormone receptor-positive, human epidermal growth factor receptor-2 negative metastatic breast cancer. Although many patients with metastatic breast cancer require palliative radiotherapy (RT), there are limited data on the safety of combining a CDK4/6 inhibitor with palliative RT., Case Report: Presented is a case of acute high-grade radiation dermatitis with low-dose palliative RT following administration of palbociclib. A 49-year-old woman with newly diagnosed hormone receptor-positive invasive ductal carcinoma of the left breast presented with lytic bone lesions in the left femur and lumbar spine. The patient initiated treatment with goserelin, tamoxifen, and palbociclib. She underwent prophylactic surgical fixation of the left femur and received post-operative RT encompassing the entire surgical nail (30 Gy/10 fractions) and palliative RT to the lumbar spine for pain relief (20 Gy/5 fractions). During cycle 4, palbociclib was stopped 3 days prior to the start of RT to reduce the risk of toxicity risk. However, 16 days after starting RT, she developed painful erythematous papules and bullae with moist desquamation on the left groin and lumbar spine., Management & Outcome: Her symptoms were managed with topical Aquaphor-lidocaine, silver sulfadiazine, and aluminum acetate soaks. Dermatitis subsided to dry desquamation within 2 weeks. The patient denied late toxicity at 11 months follow-up., Discussion: Larger retrospective or prospective studies are needed to further elucidate the safety of combined CDK4/6 inhibitors and RT. In the meantime, special precautions are warranted in patients receiving combined therapy.

Cerebral blood flow (CBF) supports brain metabolism. Diseases impair CBF, and pharmacological agents modulate CBF. Many techniques measure CBF, but phase contrast (PC) MR imaging through the four arteries supplying the brain is rapid and robust. However, technician error, patient motion, or tortuous vessels degrade quality of the measurements of the internal carotid (ICA) or vertebral (VA) arteries. We hypothesized that total CBF could be imputed from measurements in subsets of these 4 feeding vessels without excessive penalties in accuracy. We analyzed PC MR imaging from 129 patients, artificially excluded 1 or more vessels to simulate degraded imaging quality, and developed models of imputation for the missing data. Our models performed well when at least one ICA was measured, and resulted in R 2 values of 0.998-0.990, normalized root mean squared error values of 0.044-0.105, and intra-class correlation coefficient of 0.982-0.935. Thus, these models were comparable or superior to the test-retest variability in CBF measured by PC MR imaging. Our imputation models allow retrospective correction for corrupted blood vessel measurements when measuring CBF and guide prospective CBF acquisitions., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Shah, Doyle, Wood and Borzage.)

Trastuzumab emtansine (T-DM1) is a novel therapeutic for HER2+ breast cancer patients with residual disease after neoadjuvant chemotherapy. Concurrent radiotherapy (RT) is offered to a subset of patients based on results from the KATHERINE trial which showed a favorable safety profile. With emerging therapies that necessitate concurrent RT, we must closely follow rates of skin toxicity. Our first 35 patients who underwent concurrent T-DM1 treatment with breast/chest wall (CW) ± nodal irradiation are reported. Most patients (22/35) had grade 2+ toxicity and 3 patients had grade 3 toxicities. We add our experience with radiation dermatitis and concurrent T-DM1 to contribute to existing reports., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Purpose: To assess and analyze the visual outcomes of patients with retinal vein occlusions in a real-world setting with a long-term follow-up of more than 5 years., Methods: Retrospective analysis of 56 patients having retinal vein occlusions from a tertiary eye center, with a mean follow-up of 7 years was performed. Primary outcome measures were mean change in best-corrected visual acuity (BCVA) from baseline at 6 months, 1 year, 2 years, 3 years, and final visit (≥5 years), proportion of patients having BCVA better than 20/40 and worse than 20/200, and mean number of injections. Secondary outcome measures were change in central macular thickness (CMT), development of subsequent retinal vein occlusion (RVO) in same eye or the other eye, and development of neovascular complications., Results: The mean change in letter score was + 11.84 in branch RVO (BRVO), +7.14 in non-ischemic central RVO (CRVO), and -9.5 in ischemic CRVO at 1 year, which changed to + 8.57, -5 and - 24, respectively, at the end of follow-up. CMT had improved from 506 ± 98.8 μm, 576.44 ± 149 μm, and 618 ± 178.27 μm, respectively, at baseline to 267 ± 94 μm, 345.20 ± 122.61 μm, and 265.50 ± 107.75 μm, respectively, in BRVO, non-ischemic, and ischemic hemi RVO (HRVO)/CRVO groups. The total mean number of injections given in BRVO, non-ischemic CRVO, and ischemic CRVO groups were 4.6, 6.6, and 4.1, respectively. None of the patients with BRVO developed neovascular glaucoma (NVG). Non-ischemic to ischemic HRVO/CRVO conversion was noted in 4/11 eyes at a mean duration of 12.6 months. NVG was noted in 7/9 eyes (77.8%) in initial ischemic CRVO/HRVO group and 3/4 (75%) converted eyes., Conclusion: Patients with BRVO have good visual outcomes with anti-VEGF, while in CRVO results may vary considerably owing to patient compliance and treatment burden on long-term follow-up in a real-world setting., Competing Interests: None

Background: Type 1 diabetes (T1D) management is complex and associated with significant psychosocial burden. Continuous glucose monitors (CGM) can improve disease management and outcomes and introduce new or exacerbate existing psychosocial concerns. Patient-reported outcome measures (PROMs) can be used to capture this information, but there is no consensus on which PROMs should be used in pediatric CGM research., Objective: Here we describe the process to (1) identify PROMs that could be used to assess the impact of CGMs on pediatric patients with T1D, (2) implement a modified electronic Delphi (e-Delphi) methodology to arrive at an expert consensus on which PROMs are most suitable for clinical and research applications, and (3) establish a periodicity table for the administration of PROMs over time in a real-world evidence study., Methods: To identify appropriate PROMs for pediatric patients and families with T1D and CGMs, we conducted an asynchronous, e-Delphi process with a multidisciplinary group of experts from around the country. We identified candidate instruments through a literature review. The 3-round e-Delphi process was conducted via a study website, email, and web-based forms. Participants provided opinions on the usefulness of instruments, age validation, feasibility, time, and frequency of administration., Results: In total, 16 experts participated in the e-Delphi process; 4 of whom consistently participated in all 3 rounds. We identified 62 candidate instruments, which were narrowed down to 12 final PROMs across 5 domains: diabetes distress and burden (n=4), autonomy (n=2), quality of life (n=1), psychosocial (n=3), and technology acceptance (n=2). A quarterly administration schedule was developed to reduce burden on participants., Conclusions: PROMs can provide critical insights into the psychosocial well-being of patients. The specific measures identified in the paper are particularly well suited for pediatric patients with T1D using CGMs. Clinical implementation could help health care providers, patients, and families to engage in more comprehensive disease management., (©Payal Shah, Jennifer K Raymond, Juan Espinoza. Originally published in JMIR Diabetes (https://diabetes.jmir.org), 30.11.2022.)

Competing Interests: There are no conflicts of interest.

The contribution of germline copy number variants (CNVs) to risk of developing cancer in individuals with pathogenic BRCA1 or BRCA2 variants remains relatively unknown. We conducted the largest genome-wide analysis of CNVs in 15,342 BRCA1 and 10,740 BRCA2 pathogenic variant carriers. We used these results to prioritise a candidate breast cancer risk-modifier gene for laboratory analysis and biological validation. Notably, the HR for deletions in BRCA1 suggested an elevated breast cancer risk estimate (hazard ratio (HR) = 1.21), 95% confidence interval (95% CI = 1.09-1.35) compared with non-CNV pathogenic variants. In contrast, deletions overlapping SULT1A1 suggested a decreased breast cancer risk (HR = 0.73, 95% CI 0.59-0.91) in BRCA1 pathogenic variant carriers. Functional analyses of SULT1A1 showed that reduced mRNA expression in pathogenic BRCA1 variant cells was associated with reduced cellular proliferation and reduced DNA damage after treatment with DNA damaging agents. These data provide evidence that deleterious variants in BRCA1 plus SULT1A1 deletions contribute to variable breast cancer risk in BRCA1 carriers., (© 2022. The Author(s).)

Methotrexate is historically recognized as an effective treatment of pemphigus but its utility as a single or alternate steroid-sparing agent was not recognized in recent consensus recommendations in pemphigus management. We aimed to evaluate the efficacy and safety of a treatment course for pemphigus that involves methotrexate as a single or steroid-sparing agent. In a retrospective cohort study, we examined patients with pemphigus vulgaris or pemphigus foliaceus who were on ≥3 months of methotrexate therapy. Efficacy and safety were evaluated by established pemphigus disease endpoints. Of the 34 patients who met inclusion criteria, 25 (73.5%) were on glucocorticoids at time of methotrexate initiation (median follow-up: 5.4 years; median time on methotrexate: 3.7 years). An appreciable proportion achieved disease control (91.2%), with some achieving clinical remission off all systemic therapies (23.5%). For patients on glucocorticoids, median time to control was 42 days, median time to minimal steroid dose tapering (5 mg prednisone) was 161 days, and median time to complete steroid tapering was 308 days. For patients on methotrexate as a single agent, median time to control was 119 days. Among all patients, relapse commonly occurred (88.2%). At last follow-up, 26.5% were managed on topical therapies alone and 11.8% required systemic steroid therapy. Methotrexate was largely tolerated with a low incidence of adverse events leading to treatment discontinuation (2.9%). Methotrexate has the potential to be an effective and well-tolerated option for patients and may be considered for use as an alternate single or steroid-sparing agent for pemphigus., (© 2022 Wiley Periodicals LLC.)

Revesz syndrome is a rare telomeropathy characterized by bone marrow failure and exudative retinopathy. We report the case of a 2-year-old male child, initially treated with bilateral laser photocoagulation for retinopathy of prematurity. He developed exudative changes in the right eye, presumed to be Coats disease. Later, the left eye developed a total vitreous hemorrhage. Proliferative retinopathy was noted intraoperatively. Systemic features of bone marrow failure, growth retardation, and nail pigmentation were present. Genetic testing confirmed the diagnosis of Revesz syndrome. We describe our approach to diagnosis and surgical management of the case. [ Ophthalmic Surg Lasers Imaging Retina 2022;53(6): 346-348.] .

Diabetes is a uniquely quantifiable disease, and as technology and data have proliferated over the past two decades, so have the tools to manage diabetes. Patients and providers have at their disposal devices, applications, and data platforms that generate immense amounts of data, provide critical insights into a patient's disease, and allow for personalization of treatment plans. However, the proliferation of options also comes with new burdens for providers: selecting the right tool, getting buy-in from leadership, defining the business case, implementation, and maintenance of the new technology. The complexity of these steps can be overwhelming and sometimes lead to inaction, depriving providers and patients of the advantages of technology-assisted diabetes care. Conceptually, the adoption of digital health solutions can be thought of as occurring in five interconnected phases: Needs Assessment, Solution Identification, Integration, Implementation, and Evaluation. There are a number of existing frameworks to help guide much of this process, but relatively little attention has been focused on integration. Integration is a critical phase for a number of contractual, compliance, financial, and technical processes. Missing a step or doing them out of order can lead to significant delays and potentially wasted resources. To address this gap, we have developed a practical, simplified framework for integrating diabetes data and technology solutions that can guide clinicians and clinical leaders on the critical steps in adopting and implementing a new technology., Competing Interests: JE is a paid consultant for AI Health. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Espinoza, Chin, Shah, Tut and Raymond.)

Few medical devices are designed and marketed specifically for children. Instead, adult devices are often repurposed and used off-label in pediatrics. The innovation gap between pediatric and adult devices is complex and multifactorial. This review aims to summarize the medical device landscape, describe barriers to pediatric device development, and provide an update on current strategies to help overcome these limitations. Medical devices are regulated by the Food and Drug Administration. They are registered, cleared, or approved on the basis of a 3-tier risk classification system and a differentiated set of regulatory pathways. This includes some for products that receive special designations on the basis of specific aspects that warrant more rapid review and approval. Pediatric devices number only one-quarter of those developed for adults for multiple reasons. Clinically, innovators must adjust their products to address the smaller sizes, growth, and longer duration of use in children. Smaller sample sizes and population heterogeneity also challenge the ability to obtain sufficient safety data for regulatory submissions. Financial concerns stem from lower pediatric reimbursement rates coupled with a lack of nationally standardized coverage. There are a number of promising initiatives, including the Pediatric Device Consortia Program, Early Feasibility Studies, and the new System of Hospitals for Innovation in Pediatrics - Medical Devices. However, the gap will likely not be narrowed without broad cooperation across stakeholders from industry, academia, patient advocacy groups, health care providers, investors, payors, regulators, and Congress., (Copyright © 2022 by the American Academy of Pediatrics.)