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BACKGROUND: We present the results of a retrospective review of children undergoing implantation with bone-anchored hearing aids (BAHAs) at the Great Ormond Street Hospital for Children. METHODS: The case notes of 71 children undergoing BAHA placement at the Great Ormond Street Hospital for Children between December 1990 and August 2002 were reviewed. Outcome measures included hearing thresholds, incidence of fixture loss, skin reaction and need for revision. Quality of life outcomes were also measured. RESULTS: Eighty-five ears had been implanted. Fifty-four per cent of children had experienced no complications, 42 per cent had required revision surgery and 26 per cent had experienced fixture loss at some point. Young age at implantation was associated with an adverse outcome. Trauma and failure of osseointegration had been the commonest reasons for failure. A skin reaction around the abutment had occurred at some point in 37 per cent of children but had persisted for longer than six months in only 9 per cent; this had been associated with fixture loss. The use of fixture site split skin grafts had reduced problems with skin hypertrophy and hair overgrowth. Hearing thresholds when using BAHAs had been comparable to those when using bone conduction hearing aids. However, BAHAs had significant additional benefits in terms of sound quality, ease of use and overall quality of life. CONCLUSION: Bone-anchored hearing aids provide significant benefits over other types of hearing aid, both audiologically and in terms of quality of life. Careful selection of candidates and meticulous follow up are required in order to minimize complications. [ABSTRACT FROM AUTHOR]

Subglottic haemangioma is a potentially life-threatening condition for which various treatment modalities are available. The objective of this study was to evaluate our results for open excision of subglottic haemangioma. The study assessed 18 patients who had been treated at a paediatric tertiary referral centre. Most of these patients (83.3 per cent) had undergone open surgical excision without post-operative tracheostomy and had been intubated for several days post-operatively (single-stage procedure). In most of these patients (66.7 per cent), an anterior cartilage graft had been used for reconstruction. The average follow up in this study was 25 months. All the patients in this series had achieved an adequate airway after the procedure. One patient had developed a recurrence of haemangioma in the trachea at a later date. The results of open surgical excision in this study were very encouraging. Seventeen out of 18 (94.4 per cent) patients had avoided tracheostomy or had been decannulated as a direct result of surgery. One of these 18 patients (5.6 per cent) had required a temporary post-operative tracheostomy for 13 months as the subglottis cleared; this was classed as a partial success. Our experience is that open excision is a highly successful 'one stop' treatment for subglottic haemangioma, which avoids prolonged use of steroids and multiple endoscopic procedures. No patient in this series developed subglottic stenosis, which can be a significant complication of laser application. [ABSTRACT FROM AUTHOR]

Background: Control of hyperglycemia delays or prevents complications of diabetes, but many persons with diabetes do not achieve optimal control.Objective: To compare diabetes control in patients receiving nurse case management and patients receiving usual care.Design: Randomized, controlled trial.Setting: Primary care clinics in a group-model health maintenance organization (HMO).Patients: 17 patients with type 1 diabetes mellitus and 121 patients with type 2 diabetes mellitus.Intervention: The nurse case manager followed written management algorithms under the direction of a family physician and an endocrinologist. Changes in therapy were communicated to primary care physicians. All patients received ongoing care through their primary care physicians.Measurements: The primary outcome, hemoglobin A1c (HbA1c) value, was measured at baseline and at 12 months. Fasting blood glucose levels, medication type and dose, body weight, blood pressure, lipid levels, patient-perceived health status, episodes of severe hypoglycemia, and emergency department and hospital admissions were also assessed.Results: 72% of patients completed follow-up. Patients in the nurse case management group had mean decreases of 1.7 percentage points in HbA1c values and 43 mg/dL (2.38 mmol/L) in fasting glucose levels; patients in the usual care group had decreases of 0.6 percentage points in HbA1c values and 15 mg/dL (0.83 mmol/L) in fasting glucose levels (P < 0.01). Self-reported health status improved in the nurse case management group (P = 0.02). The nurse case management intervention was not associated with statistically significant changes in medication type or dose, body weight, blood pressure, or lipids or with adverse events.Conclusions: A nurse case manager with considerable management responsibility can, in association with primary care physicians and an endocrinologist, help improve glycemic control in diabetic patients in a group-model HMO. [ABSTRACT FROM AUTHOR]

Titanium osseointegrated implants for bone-anchored hearing aids (BAHAs) have been in use since 1977. A series of 32 children who received implantation since 1990 is reported. The report focuses on the surgical aspects of BAHAs, predisposing factors, and prevention of complications in an unusual pediatric population. The records of 32 children who had undergone two-stage implantation of a BAHA were retrospectively reviewed. The majority of the patients had craniofacial abnormalities. Of the 32 implantees, 29 use their BAHA at present. Five children failed to achieve osseointegration, and eight patients have had revision surgery for lost abutments, trauma, or chronic skin problems. There were no differences between preimplantation and postimplantation bone or air conduction thresholds. The pediatric BAHA carries with it a unique set of challenges and problems but can be successfully implanted and maintained. [ABSTRACT FROM AUTHOR]

Research exploring the correlates of sexual victimization has found sexual victimization to be associated with both individual- and contextual-level factors, including age, gender, poverty, and size of the female population. However, to date, research has been limited in exploring how historical factors, such as slavery, may be associated with the contemporary prevalence of sexual victimization of women. Historical accounts have often suggested that enslaved women often experienced sexual victimization during their enslavement. Despite these accounts, research has been limited in empirically exploring the relationship between slavery and the sexual victimization of Black women. Using the 1860 U.S. Census and the 2019 National Incidence-Based Reporting System, multilevel logistic regression analyses are employed to explore whether slavery is consequential for contemporary instances of Black female sexual victimization. In line with the "legacy effect" framework, the findings from the current study suggest that Black women are significantly more likely to be sexually victimized in counties characterized by larger enslaved populations in 1860. These findings illuminate how historical institutions, despite being outlawed, have contemporary consequences, particularly for Black women. These findings, discussions, avenues for future research, and policy implications are discussed below., Competing Interests: Declaration of Conflicting InterestsThe author declared no potential conflicts of interests with respect to the authorship and/or publication of this article.

Acute myeloid leukemia (AML) with fms-like tyrosine kinase 3 internal tandem duplication (FLT3-ITD) has poor outcomes. FLT3-ITD drives constitutive and aberrant FLT3 signaling, activating STAT5 and upregulating the downstream oncogenic serine/threonine kinase Pim-1. FLT3 inhibitors are in clinical use, but with limited and transient efficacy. We previously showed that concurrent treatment with Pim and FLT3 inhibitors increases apoptosis induction in FLT3-ITD-expressing cells through posttranslational downregulation of Mcl-1. Here we further elucidate the mechanism of action of this dual targeting strategy. Cytotoxicity, apoptosis and protein expression and turnover were measured in FLT3-ITD-expressing cell lines and AML patient blasts treated with the FLT3 inhibitor gilteritinib and/or the Pim inhibitors AZD1208 or TP-3654. Pim inhibitor and gilteritinib cotreatment increased apoptosis induction, produced synergistic cytotoxicity, downregulated c-Myc protein expression, earlier than Mcl-1, increased turnover of both proteins, which was rescued by proteasome inhibition, and increased efficacy and prolonged survival in an in vivo model. Gilteritinib and Pim inhibitor cotreatment of Ba/F3-ITD cells infected with T58A c-Myc or S159A Mcl-1 plasmids, preventing phosphorylation at these sites, did not downregulate these proteins, increase their turnover or increase apoptosis induction. Moreover, concurrent treatment with gilteritinib and Pim inhibitors dephosphorylated (activated) the serine/threonine kinase glycogen synthase kinase-3β (GSK-3β), and GSK-3β inhibition prevented c-Myc and Mcl-1 downregulation and decreased apoptosis induction. The data are consistent with c-Myc T58 and Mcl-1 S159 phosphorylation by activated GSK-3β as the mechanism of action of gilteritinib and Pim inhibitor combination treatment, further supporting GSK-3β activation as a therapeutic strategy in FLT3-ITD AML., Significance: FLT3-ITD is present in 25% of in AML, with continued poor outcomes. Combining Pim kinase inhibitors with the FDA-approved FLT3 inhibitor gilteritinib increases cytotoxicity in vitro and in vivo through activation of GSK-3β, which phosphorylates and posttranslationally downregulates c-Myc and Mcl-1. The data support efficacy of GSK-3β activation in FLT3-ITD AML, and also support development of a clinical trial combining the Pim inhibitor TP-3654 with gilteritinib., (© 2024 The Authors; Published by the American Association for Cancer Research.)

Objective: This study sought to (1) collate the experiences of university students with concussion history and academic stakeholders through interviews and (2) develop concussion management recommendations for institutions of higher learning using a multidisciplinary Delphi procedure., Setting: Remote semistructured interviews and online surveys., Participants: The first aim of this study included undergraduate university students with concussion history who did not participate in varsity athletics ( n = 21; 57.1% female), as well as academic faculty/staff with experience assisting university students with their postconcussion academic needs ( n = 7; 71.4% female). The second aim enrolled 22 participants (54.5% female) to serve on the Delphi panel including 9 clinicians, 8 researchers, and 5 academic faculty/staff., Design: An exploratory-sequential mixed-methods approach., Main Measures: Semistructured interviews were conducted to unveil barriers regarding the return-to-learn (RTL) process after concussion, with emergent themes serving as a general framework for the Delphi procedure. Panelists participated in 3 stages of a modified Delphi process beginning with a series of open-ended questions regarding postconcussion management in higher education. The second stage included anonymous ratings of the recommendations, followed by an opportunity to review and/or modify responses based on the group's consensus., Results: The results from the semistructured interviews indicated students felt supported by their instructors; however, academic faculty/staff lacked information on appropriate academic supports and/or pathways to facilitate the RTL process. Of the original 67 statements, 39 achieved consensus (58.2%) upon cessation of the Delphi procedure across 3 main categories: recommendations for discharge documentation (21 statements), guidelines to facilitate a multidisciplinary RTL approach (10 statements), and processes to obtain academic supports for students who require them after concussion (8 statements)., Conclusions: These findings serve as a basis for future policy in higher education to standardize RTL processes for students who may need academic supports following concussion., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: To systematically review the scientific literature regarding the acute assessment of sport-related concussion (SRC) and provide recommendations for improving the Sport Concussion Assessment Tool (SCAT6)., Data Sources: Systematic searches of seven databases from 2001 to 2022 using key words and controlled vocabulary relevant to concussion, sports, SCAT, and acute evaluation., Eligibility Criteria: (1) Original research articles, cohort studies, case-control studies, and case series with a sample of >10; (2) ≥80% SRC; and (3) studies using a screening tool/technology to assess SRC acutely (<7 days), and/or studies containing psychometric/normative data for common tools used to assess SRC., Data Extraction: Separate reviews were conducted involving six subdomains: Cognition, Balance/Postural Stability, Oculomotor/Cervical/Vestibular, Emerging Technologies, and Neurological Examination/Autonomic Dysfunction. Paediatric/Child studies were included in each subdomain. Risk of Bias and study quality were rated by coauthors using a modified SIGN (Scottish Intercollegiate Guidelines Network) tool., Results: Out of 12 192 articles screened, 612 were included (189 normative data and 423 SRC assessment studies). Of these, 183 focused on cognition, 126 balance/postural stability, 76 oculomotor/cervical/vestibular, 142 emerging technologies, 13 neurological examination/autonomic dysfunction, and 23 paediatric/child SCAT. The SCAT discriminates between concussed and non-concussed athletes within 72 hours of injury with diminishing utility up to 7 days post injury. Ceiling effects were apparent on the 5-word list learning and concentration subtests. More challenging tests, including the 10-word list, were recommended. Test-retest data revealed limitations in temporal stability. Studies primarily originated in North America with scant data on children., Conclusion: Support exists for using the SCAT within the acute phase of injury. Maximal utility occurs within the first 72 hours and then diminishes up to 7 days after injury. The SCAT has limited utility as a return to play tool beyond 7 days. Empirical data are limited in pre-adolescents, women, sport type, geographical and culturally diverse populations and para athletes., Prospero Registration Number: CRD42020154787., Competing Interests: Competing interests: CMB reports affiliations with the Cleveland Browns (National Football League) and Cleveland Monsters (American Hockey League), a board position in the Sports Neuropsychology Society, and occasional expert consulting fees. AMB reports receiving an honorarium for administrative aspects of the concussion consensus reviews and grant funding from Social Sciences and Humanities Research Council. She is also a Sport Information Resource Centre board member and Canadian Athletic Therapists Association committee member. BLB reports grants from the National Institute on Aging and National Institute of Neurological Disorders and Stroke and travel support for professional conferences. JMB reports is a part-time employee of the National Hockey League and a member of the NHL/NHLPA Concussion subcommittee. He is the neuropsychology consultant to Major League Soccer's Sporting KC and has served as a consultant to EyeGuide. JSB is supported by the University of Calgary, the Natural Sciences and Engineering Research Council (CGSD3-559333-2021), and an honorarium for the methods author work associated with Reviews two and four. GAD is a member of the Scientific Committee of the 6th International Consensus Conference on Concussion in Sport; an honorary member of the AFL Concussion Scientific Committee; Section Editor, Sport and Rehabilitation, NEUROSURGERY; and has attended meetings organised by sporting organisations including the NFL, NRL, IIHF, IOC and FIFA; however has not received any payment, research funding or other monies from these groups other than for travel costs. RJE is a paid consultant for the National Hockey League and co-chair of the National Hockey League/National Hockey League Players' Association Concussion Subcommittee, Major League Soccer’s Concussion Committee and the US Soccer Federation. He provides expert testimony in matters related to mild traumatic brain injury and reports a grant from Boston Children’s Hospital (subaward from the National Football League) and travel support for the CIS conference and other professional conferences, an unpaid board member of CISG and a member of the Scientific Committee of the 6th International Consensus Conference on Concussion in Sport. He has served in leadership roles (unpaid) in professional organisations. CCG discloses the following: Grants/Research Support: Hit-IQ (2022-2023); NIH NINDS (R01 NS110757 2019-2024); NINDS (U54 NS121688 2021-2026); UCLA Brain Injury Research Center, UCLA Steve Tisch BrainSPORT program, Easton Clinic for Brain Health Clinical Consultant (provide clinical care to athletes): NBA, NFL-Neurological Care Program, NHL/NHLPA, Los Angeles Lakers Advisory Board (non-compensated): Major League Soccer, National Basketball Association, US Soccer Federation. Advisory Board (compensated): Highmark Interactive; Medicolegal: One or two cases annually. Stock Shareholder: Highmark Interactive stock options (2018). Book royalties – Blackwell/Wiley Publishing: Prioritized Neurological Differential Diagnosis. GG Reports grant funding from CDC TEAM and OnTRACK grants, NIMH APNA grant, royalties from PAR, consulting fees from NFL Baltimore Ravens, Zogenix International and Global Pharma Consultancy, and travel support for professional meetings. He is a member of USA Football Medical Advisory Panel. KMG reports compensation from National Collegiate Athletic Association for other services and grants from Boston Children’s Hospital (subaward from the National Football League). SH is co-founder and senior advisor, The Sports Institute at UW Medicine (unpaid), Centers for Disease Control and Prevention and National Center for Injury Prevention and Control Board Pediatric Mild Traumatic Brain Injury Guideline Workgroup (unpaid), CISG (travel support), NCAA Concussion Safety Advisory Group (unpaid), Team Physician, Seattle Mariners, Former Team Physician, Seattle Seahawks, occasional payment for expert testimony, travel support for professional meetings. DH reports research support from the Eunice Kennedy Shriver National Institute of Child Health & Human Development, the National Institute of Neurological Disorders And Stroke, the National Institute of Arthritis and Musculoskeletal and Skin Diseases, 59th Medical Wing Department of the Air Force, MINDSOURCE Brain Injury Network, the Tai Foundation and the Colorado Clinical and Translational Sciences Institute (UL1 TR002535‐05) and he serves on the Scientific/Medical Advisory Board of Synaptek. Concussion research grant support from Football Research. MM reports grants/contracts from Florey Institute of Neuroscience and Mental Health, consulting fees from AFL, Olympic Park Sports Medicine Centre, Cabrini and Epworth Health, World Rugby, Hawthorn Football Club and AFL Doctors Association. He has received travel support for attending professional conferences, has/had leadership roles in CISG, International Consensus Conference in Sport meeting and Australian Rugby Union, a shareholder in Olympic Park Sports Medicine Centre, and honorary research associations with several university groups. SK reports that he is Medical Services Director, Rugby Football Union. CLM reports no financial COI. She holds leadership positions with several organisations: American College of Sports Medicine, American Medical Society for Sports Medicine, Pediatric Research in Sports Medicine, Council on Sports Medicine and Fitness, American Academy of Pediatrics, Untold Foundation, Pink Concussions, Headway Foundation and the editorial boards of Journal of Adolescent Health, Frontiers in Neuroergonomics, Exercise, Sport and Movement. WPM receives royalties from ABC-Clio publishing, Springer International and Wolters Kluwer. His research is funded by philanthropic support from the National Hockey League Alumni Association through the Corey C. Griffin Pro-Am Tournament and a grant from the National Football League. DN receives consulting fees from the CFL and travel support for professional conferences. He is a team physician for the NHL and CFL. He is CMO for the CFL and a member of NHL and CFL committees. JP Editor BJSM (honorarium). Member of World Rugby Concussion Advisory Group (unpaid). Independent Concussion Consultant for World Rugby (fee per consultation) Medical consultant to South African Rugby (unpaid). Co-chair of the Scientific Committee, 6th International Conference on Concussion in Sport (unpaid). Board member of the Concussion in Sport Group (unpaid). Scientific Board member, EyeGuideTM (unpaid). MP reports receiving a travel stipend for attending CIS meeting and other professional conferences, grant funds from NCAA-CARE 2.0, royalties from Netters’ Sports Medicine, consulting fees from Major League Soccer as CMO and occasional expert testimony. She is a member of several professional boards and advisory panels. KJS has received grant funding from the Canadian Institutes of Health Research, National Football League Scientific Advisory Board, International Olympic Committee Medical and Scientific Research Fund, World Rugby, Mitacs Accelerate, University of Calgary with funds paid to her institution and not to her personally. She is an Associate Editor of BJSM (unpaid) and has received travel and accommodation support for meetings where she has presented. She is coordinating the writing of the systematic reviews that will inform the 6th International Consensus on Concussion in Sport, for which she has received an educational grant to assist with the administrative costs associated with the writing of the reviews. She is a member of the AFL Concussion Scientific Committee (unpaid position) and Brain Canada (unpaid positions). She works as a physiotherapy consultant and treats athletes of all levels of sport from grass roots to professional. JvI reports CIHR Postdoctoral Fellowship Award, UOMBRI Grant, travel stipend from CTRC and Founder of R2P Concussion Management. TCVM is a paid member of the NFL Head, Neck and Spine Committee and an unpaid member of the USA Swimming Concussion Task Force. SRW reports honoraria and travel support for professional meetings and leadership positions in World Federation of Athletic Training and Therapy and Outcomes, International Traumatic Brain Injury Research Initiative. DS reports grants from World Rugby, New Zealand Rugby Foundation and Otago Science into Action. JK, NB, JCA-L, ZP: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Sport-related concussions (SRCs) affect millions of adolescents and young adults annually in the USA; however, current SRC consensus statements provide limited guidance on academic support for students within higher education., Objective: To generate consensus on appropriate academic recommendations for clinicians, students, and academic stakeholders to support university students during their recovery., Methods: Panelists participated in three stages of a modified Delphi procedure: the first stage included a series of open-ended questions after reviewing a literature review on post-SRC return-to-learn (RTL) in higher education; the second stage asked panelists to anonymously rate the recommendations developed through the first Delphi stage using a 9-point scale; and the final stage offered panelists the opportunity to change their responses and/or provide feedback based on the group's overall ratings., Results: Twenty-two panelists including clinicians, concussion researchers, and academic stakeholders (54.5% female) from 15 institutions and/or healthcare systems participated in a modified Delphi procedure. A total of 42 statements were developed after round one. Following the next two rounds, 27 statements achieved consensus amongst the panel resulting in the four-stage Post-Concussion Collegiate RTL Protocol., Conclusion: There are several unique challenges when assisting university students back to the classroom after SRC. Explicit guidelines on when to seek additional medical care (e.g., if they are experiencing worsening or persistent symptoms) and how to approach their instructor(s) regarding academic support may help the student self-advocate. Findings from the present study address barriers and provide a framework for universities to facilitate a multidisciplinary approach amongst medical and academic stakeholders., (© 2022. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Background: Lower extremity salvage in the setting of severe trauma requires the consideration of multiple surgical specialties and treatment algorithms. We hypothesized that time to first ambulation, ambulation without an assistive device, chronic osteomyelitis, and delayed amputation were not affected by the time to soft tissue coverage in Gustilo IIIB and IIIC fractures at our institution., Methods: We evaluated all patients treated for open tibia fractures at our institution from 2007 to 2017. Patients requiring any form of soft tissue coverage to the lower extremity during their initial hospitalization and who had at least 30 days of follow-up from time of hospital discharge were included. Univariable and multivariable analysis was performed for all variables and outcomes of interest., Results: Of 575 patients included, 89 required soft tissue coverage. On multivariable analysis, the time to soft tissue coverage, length of negative pressure wound therapy treatment, and number of wound washouts were not found to be associated with development of chronic osteomyelitis, decreased 90-day return to any ambulation, decreased 180-day return to ambulation without assistive device, or delayed amputation., Conclusions: Time to soft tissue coverage in open tibia fractures did not affect time to first ambulation, ambulation without an assistive device, chronic osteomyelitis, or delayed amputation in this cohort. It remains difficult to definitively prove that time to soft tissue coverage meaningfully impacts lower extremity outcomes., Competing Interests: Disclosures: The authors disclosed no conflicts of interest., (© 2022, HMP Global. All rights reserved. Reproduction in whole or in part prohibited. Content may not be reproduced in any form without written permission. Rights, Permission, Reprint, and Translation information is available at www.hmpglobal.com.)

BACKGROUNDCOVID-19 remains a global health emergency with limited treatment options, lagging vaccine rates, and inadequate healthcare resources in the face of an ongoing calamity. The disease is characterized by immune dysregulation and cytokine storm. Cyclosporine A (CSA) is a calcineurin inhibitor that modulates cytokine production and may have direct antiviral properties against coronaviruses.METHODSTo test whether a short course of CSA was safe in patients with COVID-19, we treated 10 hospitalized, oxygen-requiring, noncritically ill patients with CSA (starting at a dose of 9 mg/kg/d). We evaluated patients for clinical response and adverse events, measured serum cytokines and chemokines associated with COVID-19 hyperinflammation, and conducted gene-expression analyses.RESULTSFive participants experienced adverse events, none of which were serious; transaminitis was most common. No participant required intensive care unit-level care, and all patients were discharged alive. CSA treatment was associated with significant reductions in serum cytokines and chemokines important in COVID-19 hyperinflammation, including CXCL10. Following CSA administration, we also observed a significant reduction in type I IFN gene expression signatures and other transcriptional profiles associated with exacerbated hyperinflammation in the peripheral blood cells of these patients.CONCLUSIONShort courses of CSA appear safe and feasible in patients with COVID-19 who require oxygen and may be a useful adjunct in resource-limited health care settings.TRIAL REGISTRATIONThis trial was registered on ClinicalTrials.gov (Investigational New Drug Application no. 149997; ClinicalTrials.gov NCT04412785).FUNDINGThis study was internally funded by the Center for Cellular Immunotherapies.

A combination of anti-CTLA-4 plus anti-PD-1/PD-L1 is the most effective cancer immunotherapy but causes high incidence of immune-related adverse events (irAEs). Here we report that targeting of HIF-1α suppressed PD-L1 expression on tumor cells and tumor-infiltrating myeloid cells, but unexpectedly induced PD-L1 in normal tissues by an IFN-γ-dependent mechanism. Targeting the HIF-1α/PD-L1 axis in tumor cells reactivated tumor-infiltrating lymphocytes and caused tumor rejection. The HIF-1α inhibitor echinomycin potentiated the cancer immunotherapeutic effects of anti-CTLA-4 therapy, with efficacy comparable to that of anti-CTLA-4 plus anti-PD-1 antibodies. However, while anti-PD-1 exacerbated irAEs triggered by ipilimumab, echinomycin protected mice against irAEs by increasing PD-L1 levels in normal tissues. Our data suggest that targeting HIF-1α fortifies the immune tolerance function of the PD-1/PD-L1 checkpoint in normal tissues but abrogates its immune evasion function in the tumor microenvironment to achieve safer and more effective immunotherapy.

Background: The impact of breast reconstruction on financial toxicity remains poorly understood despite growing awareness. The authors sought to illustrate the relationship between breast reconstruction subtypes and the risk of financial toxicity., Methods: The authors conducted a single-institution cross-sectional survey of all female breast cancer patients undergoing any form of breast reconstruction between January of 2018 and June of 2019. Financial toxicity was measured by means of the validated Comprehensive Score for Financial Toxicity instrument. Demographics, clinical course, and coping strategies were abstracted from a purpose-built survey and electronic medical records. Multivariable linear regression was performed to identify associations with financial toxicity., Results: The authors' analytical sample was 350 patients. One hundred eighty-four (52.6 percent) underwent oncoplastic reconstruction, 126 (36 percent) underwent implant-based reconstruction, and 40 (11.4 percent) underwent autologous reconstruction. Oncoplastic reconstruction recipients were older, had a higher body mass index, and were more likely to have supplemental insurance and receive adjuvant hormonal therapy. No significant differences in the risk of financial toxicity were uncovered across breast reconstruction subtypes (p = 0.53). Protective factors against financial toxicity were use of supplemental insurance (p = 0.0003) and escalating annual household income greater than $40,000 (p < 0.0001). Receipt of radiation therapy was positively associated with worsening financial toxicity (-2.69; 95 CI percent, -5.22 to -0.15). Financial coping strategies were prevalent across breast reconstruction subtypes., Conclusions: Breast reconstruction subtype does not differentially impact the risk of financial toxicity. Increasing income and supplemental insurance were found to be protective, whereas receipt of radiation therapy was positively associated with financial toxicity. Prospective, multicenter studies are needed to identify the main drivers of out-of-pocket costs and financial toxicity in breast cancer care., (Copyright © 2021 by the American Society of Plastic Surgeons.)

Overweight and obesity present health risks for mothers and their children. Reaching women during the key life stages of preconception and pregnancy in community settings, such as workplaces, is an ideal opportunity to enable health behavior change. We conducted five focus groups with 25 women aged between 25 and 62 years in order to investigate the determinants of healthy lifestyle behaviors, weight management, and wellbeing needs during the preconception and pregnancy periods in an Australian university workplace. Discussions explored women's health and wellbeing needs with specific reference to workplace impact. An abductive analytical approach incorporated the capability, opportunity, and motivation of behavior (COM-B) model, and four themes were identified: hierarchy of needs and values, social interactions, a support scaffold, and control. Findings highlight the requirement for greater organization-level support, including top-down coordination of wellbeing opportunities and facilitation of education and support for preconception healthy lifestyle behaviors in the workplace. Interventionists and organizational policy makers could incorporate these higher-level changes into workplace processes and intervention development, which may increase intervention capacity for success.

Fms -like tyrosine-like kinase 3 internal tandem duplication (FLT3-ITD) is present in acute myeloid leukemia (AML) in 30% of patients and is associated with short disease-free survival. FLT3 inhibitor efficacy is limited and transient but may be enhanced by multitargeting of FLT3-ITD signaling pathways. FLT3-ITD drives both STAT5-dependent transcription of oncogenic Pim-1 kinase and inactivation of the tumor-suppressor protein phosphatase 2A (PP2A), and FLT3-ITD, Pim-1, and PP2A all regulate the c-Myc oncogene. We studied mechanisms of action of cotreatment of FLT3-ITD-expressing cells with FLT3 inhibitors and PP2A-activating drugs (PADs), which are in development. PADs, including FTY720 and DT-061, enhanced FLT3 inhibitor growth suppression and apoptosis induction in FLT3-ITD-expressing cell lines and primary AML cells in vitro and MV4-11 growth suppression in vivo PAD and FLT3 inhibitor cotreatment independently downregulated c-Myc and Pim-1 protein through enhanced proteasomal degradation. c-Myc and Pim-1 downregulation was preceded by AKT inactivation, did not occur in cells expressing myristoylated (constitutively active) AKT1, and could be induced by AKT inhibition. AKT inactivation resulted in activation of GSK-3β, and GSK-3β inhibition blocked downregulation of both c-Myc and Pim-1 by PAD and FLT3 inhibitor cotreatment. GSK-3β activation increased c-Myc proteasomal degradation through c-Myc phosphorylation on T58; infection with c-Myc with T58A substitution, preventing phosphorylation, blocked downregulation of c-Myc by PAD and FLT3 inhibitor cotreatment. GSK-3β also phosphorylated Pim-1L/Pim-1S on S95/S4. Thus, PADs enhance efficacy of FLT3 inhibitors in FLT3-ITD-expressing cells through a novel mechanism involving AKT inhibition-dependent GSK-3β-mediated increased c-Myc and Pim-1 proteasomal degradation., (©2021 American Association for Cancer Research.)

Background: Rising out-of-pocket costs (OOCs) are a major concern for breast cancer survivors. However, information on how plastic surgeons performing breast reconstruction (BR) perceive and communicate cost information is limited., Methods: An electronic, anonymous survey eliciting plastic surgeons' attitudes and behaviors regarding BR cost communication was distributed to active American Society of Plastic Surgery members. Questions were derived from previously published studies and entailed a 5-point Likert scale. Cost communication was identified based on dichotomized responses to the prompt, "I discuss the costs of breast reconstruction with my patients," and analyzed for associated factors., Results: Of the 5112 surgeons surveyed, 396 plastic surgeons responded (7.21%). Most of the surgeons reported having a sense of a patient's financial well-being (65%) and an awareness of treatment costs (66.9%). Most felt a responsibility to consider the impact of BR costs (69%). Although most of the surgeons expressed that they were comfortable having OOC discussions (58.9%), only a minority reported doing so routinely (24.2%). The fewest respondents (8.6%) cited OOC as an important variable for BR decision-making. Lack of supportive tools was the most cited barrier to having cost communication with patients (64.8%). Cost communication was identified in a minority (20.2%) of surgeon-patient encounters and had no significant relationship to surgeon demographics or practice setting., Conclusions: Plastic surgeons rarely discuss costs of BR with patients despite having a high awareness of the topic and feeling comfortable with it. Prevailing attitudes about the importance of OOC and the lack of administrative support or cost information are likely the drivers of this mismatch and warrant further study.

Background and Objectives: Sarcopenia is an objective measure of patient frailty and is a predictor of adverse surgical outcomes. We hypothesized that sarcopenia is associated with increased surgical site occurrence (SSO) and hernia occurrences in patients undergoing oncologic abdominal wall reconstruction., Methods: Consecutive patients who underwent abdominal wall reconstruction (AWR) for an abdominal wall ablative defect at a single center from 2005 to 2015 were evaluated. The total psoas index (TPI) was used to define sarcopenia. The primary endpoint of the study was hernia occurrence; (SSO) was a secondary outcome measure., Results: Eighty-six patients met the inclusion criteria. Multivariate analysis demonstrated that sarcopenia increased the risk of hernia more than threefold, trending toward significance (OR = 3.3; 95% CI: 0.69-15.4; P = .13). Multivariate logistic regression demonstrated that preoperative radiotherapy (OR = 4.8, 95% CI: 1.4-16; P = .01) and obesity (OR = 4.9, 95% CI: 1.5-16.3; P =.009) were independent predictors of developing an SSO., Conclusions: Sarcopenia, as defined by TPI, is correlated with hernia occurrence, but not SSO. These findings emphasize the importance of preoperative fitness and nutritional optimization and provide useful information for preoperative counseling and risk stratification., (© 2020 Wiley Periodicals LLC.)

Introduction: Compression is integral to the management of edema and the prevention of venous leg ulcers (VLUs)., Objective: The aim of this study is to assess the sub-bandage pressure distribution under 3 compression applications as well as to assess the impact of an innovative primary wound dressing, applied under the compression products, on pressure distribution., Materials and Methods: A series of controlled tests were performed using a simulated leg model (SLM). A pressure mapping sensor and system software was used to measure the interface pressure (IP) and pressure distribution created by the application of 3 different compression systems with and without the addition of an elastic longitudinal stockinette (fuzzy wale compression; FWC). These included: (1) 2-layer cohesive wrap; (2) 3-layer compression application; and (3) 4-layer compression application. The IP was pressure between the SLM and the innovative dressing over which the compression applications were applied. Seven different configurations were tested, including the compression applications alone and in combination with the FWC. In addition to the IP measurements, pressure mapping visualizations were captured with the pressure mapping sensor and system software. A custom MATLAB program was written for data analysis, differentiations in discrete high- and low-pressure locations across the compressed area, and graphing of the pressure readings., Results: The overall average pressure for each testing setup without FWC ranged from 34.65 ± 4.84 mm Hg for the 2L configuration to 63.92 ± 7.08 mm Hg for the 4L configuration. The addition of the FWC resulted in a 19% increase for the 2L, 9% increase for the 3L, and 7% increase for the 4L compression systems. Additionally, it was noted that the inclusion of FWC resulted in a significant change in pressures vertically oriented under the 2-, 3-, and 4-layer compression applications of 34.52 ± 9.06 mm Hg, 99.21 ± 29.81 mm Hg, and 128.96 ± 22.97 mm Hg, respectively. The pressure distribution under the compression alone was observed to be largely uniform except for areas of overlap that produce horizontal bands of elevated pressures. The presence of the primary wound dressing did not have a significant impact on the IP measurements. The addition of FWC to all compression applications demonstrated a vertical distribution of compression along the sensor with alternating areas of little or no compression., Conclusions: The unique alternating pressure distribution observed in the in vitro pressure testing with the use of FWC in a clinical setting has been observed to produce better edema management and wound edge migration that mirrors the vertical pressure distribution observed in the study. Additional in vitro and in vivo research to evaluate the biophysical impact of IP created by the use of a combination of primary wound dressings and compression applications with focus on the total pressure and the distribution across the surface of intact tissue and open wound bed is warranted.

Background: Surgical specialists in plastic, head and neck, hand, trauma surgery, and emergency medicine physicians bear the burden of treating the most serious injuries caused by animals. Most of these incidents result from an attack by a known dog, and breed has been proposed, but not proven, to be a controllable factor. The authors summarize the peer-reviewed literature on dog bites in the United States, specifically as related to the breeds implicated., Methods: A systematic review of all peer-reviewed publications reporting on dog bites in the United States was performed. MEDLINE, Embase, Scopus, Google Scholar, and Cochrane Library searches were conducted through May 8, 2018, for studies from the United States implicating a specific dog breed as responsible., Results: Forty-one articles met inclusion criteria, the majority of which were single-institution retrospective reviews. Main outcomes were any dog bite reported in the peer-reviewed literature where a specific breed was implicated. Secondary measures included dog bites reported in areas where breed-specific legislation was enacted. The most common pure breed identified was German Shepherd, followed by Pit Bull-type breeds (i.e., American Staffordshire Terrier, American Pit Bull Terrier, Staffordshire Bull Terrier, American Bully), Labrador, Collie, and Rottweiler, respectively. Pit bull-type and German Shepherd breeds are consistently implicated for causing the most serious injuries to patients in the United States across heterogeneous populations, and this remained consistent across multiple decades., Conclusions: The authors' results indicate that German Shepherd and Pit Bull-type breeds account for the largest subset of pure breeds implicated in severe dog bites inflicted on humans in the medical literature. The role and complexity of mentioning breed in relation to human injuries are also discussed.

American schools have become increasingly punitive and characterized by racial and ethnic disparities in punishment outcomes. Scholarship on the causes and consequences of this shift has highlighted the potential salience of school context. The current study extends this work by exploring the potential effect of an underexplored factor, teacher diversity, on suspension disparities. To date, explorations of the role of teacher diversity have been limited to its impact on academic outcomes, teacher perceptions, and behavioral outcomes. The current study fills a void in the existing literature by examining (1) whether greater teacher diversity is associated with reductions in racial and ethnic suspension disparities and (2) whether greater teacher diversity interacts with the size of the racial and ethnic student population to influence suspension disparities. This study contributes to the existing literature by extending the "value in diversity" perspective to the school setting. Additionally, the findings suggest that racial and ethnic diversity in positions of authority in the school setting fosters a more equitable approach to the administration of student punishment., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective : Children with asthma have ongoing health care needs and health insurance is a vital part of their health care access. Health care coverage may be associated with various cost barriers to asthma care. We examined cost barriers to receiving asthma care by health insurance type and coverage continuity among children with asthma using the 2012-2014 Child Asthma Call-back Survey (ACBS). Methods : The study sample included 3788 children under age 18 years with current asthma who had responses to the ACBS by adult proxy. Associations between cost barriers to asthma care and treatment were analyzed by demographic, health insurance coverage, and urban residence variables using multivariable logistic regression models. Results : Among insured children, more blacks reported a cost barrier to seeing a doctor (10.6% [5.9, 18.3]) compared with whites (2.9% [2.1, 4.0]) ( p  = 0.03). Adjusting for demographic factors (sex, age, and race), uninsured and having partial year coverage were associated with cost barrier to seeing a doctor (adjusted prevalence ratio aPR = 8.07 [4.78, 13.61] and aPR = 6.58 [3.78, 11.45], respectively) and affording medication (aPR = 8.35 [5.23, 13.34] and aPR = 4.93 [2.96, 8.19], respectively), compared with children who had full year coverage. Public insurance was associated with cost barrier to seeing a doctor (aPR = 4.43 [2.57, 7.62]), compared with private insurance. Conclusions : Having no health insurance, partial year coverage, and public insurance were associated with cost barriers to asthma care. Improving health insurance coverage may help strengthen access to and reduce cost barriers to asthma care.

Hypoxia-inducible factor 1α (HIF-1α) is recognized as a prime molecular target for metastatic cancer. However, no specific HIF-1α inhibitor has been approved for clinical use. Here, we demonstrated that in vivo efficacy of echinomycin in solid tumors with HIF-1α overexpression is formulation-dependent. Compared to previously-used Cremophor-formulated echinomycin, which was toxic and ineffective in clinical trials, liposomal-echinomycin provides significantly more inhibition of primary tumor growth and only liposome-formulated echinomycin can eliminate established triple-negative breast cancer (TNBC) metastases, which are the leading cause of death from breast cancer, as available therapies remain minimally effective at this stage. Pharmacodynamic analyses reveal liposomal-echinomycin more potently inhibits HIF-1α transcriptional activity in primary and metastasized TNBC cells in vivo, the latter of which are HIF-1α enriched. The data suggest that nanoliposomal-echinomycin can provide safe and effective therapeutic HIF-1α inhibition and could represent the most potent HIF-1α inhibitor in prospective trials for metastatic cancer., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objectives: The literature on fluid biomarkers for concussion has primarily focused on comparing athletes with and without a diagnosis of concussion and on examining the relationship between fluid biomarkers and exposure to head trauma. This systematic literature review aims to examine the strength of evidence for fluid biomarkers to be associated with clinically relevant outcomes in sports-related concussion., Methods: A systematic literature review was conducted using EmBASE, PubMed, and CINAHL. English-language articles that included athletes participating in organized sports and reported the relationship between at least one fluid biomarker and at least one clinical outcome measure, or provided data that could be used to analyze this relationship, were included., Results: Studies of the relationship between fluid biomarkers and clinical outcomes of concussion have yielded small or variable effects. There were significant inconsistencies in methodology including duration of time post-injury of biomarker collection, use of control groups, the number of time points post-injury that biomarkers were collected, and what clinical outcomes were utilized., Conclusion: There is currently insufficient evidence to support a relationship between any of the included fluid biomarkers and clinical outcome measures of concussion. Future research including clinical outcome measures and using standardized study design and methodology is necessary.

Background: Visual estimation of blood loss following delivery often under-reports actual bleed volume. To improve accuracy, quantitative blood loss measurement was introduced for all births in the 12 hospitals providing maternity care in Wales. This intervention was incorporated into a quality improvement programme (Obstetric Bleeding Strategy for Wales, OBS Cymru). We report the incidence of postpartum haemorrhage in Wales over a 1-year period using quantitative measurement., Methods: This prospective, consecutive cohort included all 31,341 women giving birth in Wales in 2017. Standardised training was cascaded to maternity staff in all 12 hospitals in Wales. The training comprised mock-scenarios, a video and team drills. Uptake of quantitative blood loss measurement was audited at each centre. Data on postpartum haemorrhage of > 1000 mL were collected and analysed according to mode of delivery. Data on blood loss for all maternities was from the NHS Wales Informatics Service., Results: Biannual audit data demonstrated an increase in quantitative measurement from 52.1 to 87.8% (P < 0.001). The incidence (95% confidence intervals, CI) of postpartum haemorrhage of > 1000 mL, > 1500 mL and > 2000 mL was 8.6% (8.3 to 8.9), 3.3% (3.1 to 3.5) and 1.3% (1.2 to 1.4), respectively compared to 5%, 2% and 0.8% in the year before OBS Cymru. The incidence (95% CI) of bleeds of > 1000 mL was similar across the 12 hospitals despite widely varied size, staffing levels and case mix, median (25th to 75th centile) 8.6% (7.8-9.6). The incidence of PPH varied with mode of delivery and was mean (95% CI) 4.9% (4.6-5.2) for unassisted vaginal deliveries, 18.4 (17.1-19.8) for instrumental vaginal deliveries, 8.5 (7.7-9.4) for elective caesarean section and 19.8 (18.6-21.0) for non-elective caesarean sections., Conclusions: Quantitative measurement of blood loss is feasible in all hospitals providing maternity care and is associated with detection of higher rates of postpartum haemorrhage. These results have implications for the definition of abnormal blood loss after childbirth and for management and research of postpartum haemorrhage.

Objective: This study assessed health-related quality of life (HRQoL) and related risk factors among adults with asthma in the United States. Using the 2015 Behavioral Risk Factor Surveillance System (BRFSS), we examined the association between four domains of impaired HRQoL and selected explanatory factors., Methods: A BRFSS sample of 39,321 adults with asthma was used in this study. We examined the association between fair/poor health, ≥ 14 mentally unhealthy days, ≥ 14 physically unhealthy days, and ≥ 14 days of activity limitation and selected explanatory variables (sex, race/ethnicity, age, annual household income, healthcare coverage, physical activity, smoking status, body mass index (BMI), having a coexisting disease, and being diagnosed with depression) using multivariable logistic regression models., Results: Income, physical activity status, smoking status, coexisting diseases, and depression were strongly associated with all HRQoL domains. Blacks had significantly less ≥ 14 physically unhealthy days (23.4%; aPR = 0.82 [95% confidence interval (CI): 0.72, 0.92]) and ≥ 14 days of activity limitation (18.3%; aPR = 0.81 [0.70, 0.94]) and Hispanics had significantly more fair/poor health (38.4%; aPR = 1.31 [1.18, 1.45]) than whites. Underweight and obese had significantly more fair/poor health, and underweight significantly more ≥ 14 physically unhealthy days, compared with normal weight. Adults aged 55 years or older had significantly less ≥ 14 mentally unhealthy days than adults 18-24 years., Conclusions: Multiple factors were associated with impaired HRQoL. Providing strategies to address potential risk factors such as low income, physically inactive, smoker, and obese or underweight should be considered to improve HRQoL among adults with asthma.

Background: Childbearing women commonly access maternity services via the telephone. A midwife receiving these calls listens to the woman's concerns and then triages women according to their assessment. This may result in the provision of advice and instruction over the telephone or inviting the woman into the health service for further assessment. Midwives are responsible for all care and advice given to women, including via the telephone., Objectives: The purpose of this study was to explore the experiences and practices of midwives regarding their management of telephone triage., Design: A cross-sectional survey., Setting and Participants: Purposive non-probabilistic sampling of currently practising midwife members of professional organisations was used to recruit participants. From this, 242 midwives responded and 230 returned valid surveys were used in data analysis., Methods: Participant demographics, telephone triage processes, skills, educational preparation, confidence and anxiety levels, and external factors that influence midwives' management of telephone triage were collected via an on-line survey. Descriptive statistics and further analyses were conducted to explore relationships between variables., Results: Eighty-three percent of midwives respond to 2-5 telephone calls per shift, with only 11.7% (n = 24) of midwives reporting that this is included in their workloads. Telephone triage is frequently managed in environments with distractions. Most midwives (84%; n = 177) report receiving no training in this skill. Confidence in performing telephone triage was reported, with higher confidence levels related to midwives' increased years of experience (p < 0.05) and age (p <  0.01). Anxiety related to managing telephone triage has been experienced by 73% (n = 151) of midwives, with this being greater in midwives with less years of experience. Anxiety is reported less by midwives in rural or remote settings compared to metropolitan or regional (p <  0.05) settings in this study. A variety of standards and aids to guide practice, and document calls are utilised in a range of ways., Conclusion: To the authors' knowledge, this is the first study conducted to explore midwives' practises in telephone triage. The findings suggest the need for appropriate environments to conduct telephone calls and the inclusion of telephone triage in midwifery workloads. In addition, consistent education and processes are required to reduce anxiety and support midwives provision of this service to women., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Objective: Asthma affects six million children in the United States. Most people can control their asthma symptoms with effective care, management, and appropriate medical treatment. Information on the relationship between asthma control and quality of life indicators and health care use among school-age children is limited., Methods: Using the 2006-2010 combined Behavior Risk Factor Surveillance System Asthma Call-back Survey child data, we examined asthma control and asthma attack status among school-age (aged 5-17 years) children with asthma from 35 states and the District of Columbia. Multivariable logistic regression models were used to assess if having uncontrolled asthma and having ≥1 asthma attacks affect quality of life (activity limitation and missed school days) and healthcare use (emergency department [ED] visits and hospitalizations)., Results: About one-third (36.5%) of the 8,484 respondents with current asthma had uncontrolled asthma and 56.8% reported ≥1 asthma attack in the past year. Having uncontrolled asthma and having ≥1 asthma attack were significantly associated with activity limitation (aPR = 1.43 and 1.74, respectively), missed school (1.45 and 1.68), ED visits (2.05 and 4.78), and hospitalizations (2.38 and 3.64). Long-term control (LTC) medication use was higher among respondents with uncontrolled asthma (61.3%) than respondents with well-controlled asthma (33.5%)., Conclusions: Having uncontrolled asthma is associated with reduced quality of life and increased health care use. However, only 61.3% of respondents with uncontrolled asthma use LTC medications. Increasing use of LTC medications among children with uncontrolled asthma could help improve quality of life and reduce health care use.

The Asthma Call-back Survey (ACBS) is conducted after the Behavioral Risk Factor Surveillance System (BRFSS) survey by calling BRFSS respondents who reported ever being diagnosed with asthma. To find response patterns and increase ACBS response rates, we first examined whether obtaining consents during the BRFSS survey could increase call back response rates by reducing the refusal and break-off. Then, we assessed how the lag days between BRFSS and ACBS interviews affected response rates. BRFSS cell phone respondents agreed more often to being called back than did landline respondents (75.5 vs. 70.9 percent). However, when respondents were contacted for ACBS, the cell phone response rate was lower than landline response rate (43.4 vs. 47.0 percent), except among males aged 25-34 years, for which the cell phone response rate was 2.1 percent higher than the landline response rate. ACBS response rate for landline and cell phone response were highest if the callback was within 2 days of BRFSS interviews (92.3 vs. 88.8 percent). As lag days increased, the response rate decreased. The cell phone response rate showed a sharper drop; after 2 weeks, the response rate gap between landline and cell phone samples reached 17.3 percent.