A review of the mesotheliogenic potency of cleavage fragments found in talc.

It has long been recognized that amphibole minerals, such as cleavage fragments of tremolite and anthophyllite, may exist in some talc deposits. We reviewed the current state of the science regarding the factors influencing mesotheliogenic potency of cleavage fragments, with emphasis on those that may co-occur in talc deposits, including dimensional and structural characteristics, animal toxicology, and the most well-studied cohort exposed to talc-associated cleavage fragments. Based on our review, multiple lines of scientific evidence demonstrate that inhaled cleavage fragments associated with talc do not pose a mesothelioma hazard.

Opioid Prescribing Patterns Following Lateral Skull Base Spontaneous Cerebrospinal Fluid Leak Repair.

OBJECTIVE: To characterize the opioid prescribing patterns for and requirements of patients undergoing repair of spontaneous cerebrospinal fluid (sCSF) leaks of the lateral skull base. STUDY DESIGN: Retrospective chart review. SETTING: Tertiary referral center. PATIENTS: Adults with lateral skull base sCSF leaks who underwent repairs between September 1, 2014, and December 31, 2020. MAIN OUTCOME MEASURE: Mean morphine milligram equivalents (MMEs) of opioids dispensed to inpatients and prescribed at discharge, additional pain control medications dispensed, and outpatient additional opioid requests were compared between groups. RESULTS: Of 78 patients included, 46 (59%) underwent repair via a transmastoid (TM), 6 (7.7%) via a middle cranial fossa (MCF), and 26 (33.3%) via a combined TM-MCF approach. Inpatients received a mean of 21.3, 31.4, and 37.6 MMEs per day during admission for the TM, MCF, and combined TM-MCF approaches, respectively ( p = 0.019, ηp 2 = 0.101). Upon discharge, nearly all patients (n = 74, 94.9%) received opioids; 27.3, 32.5, and 37.6 MMEs per day were prescribed after the TM, MCF, and TM-MCF approaches, respectively ( p = 0.015, ηp 2 = 0.093). Five (6.4%) patients requested additional outpatient pain medication, after which three were prescribed 36.7 MMEs per day. Patients with idiopathic intracranial hypertension required significantly more inpatient MMEs than those without (41.5 versus 25.2, p = 0.02, d = 0.689), as did patients with a history of headaches (39.6 versus 23.6, p = 0.042, d = 0.684). CONCLUSIONS: Patients undergoing sCSF leak repair via the MCF or TM-MCF approaches are prescribed more opioids postoperatively than patients undergoing the TM approach. Patients with a history of headaches or idiopathic intracranial hypertension might require more opioids postoperatively.

Not Dandy Walker variant: a review of prominent retrocerebellar CSF space in children.

The prominent retrocerebellar cerebrospinal fluid (CSF) space can be frequently encountered on paediatric neuroimaging studies. In cases involving abnormal vermian development where imaging does not align with the established criteria of Dandy-Walker malformation (DWM), the term "Dandy-Walker variant or continuum" has been historically employed to describe the aberrant posterior fossa development. Instead, the emphasis is on a more elaborate description of the findings in the posterior fossa. Moreover, combining the findings in the supratentorial brain can occasionally predict certain neurogenetic disorders that mimic Dandy-Walker phenotype. The present review demonstrates and differentiates the imaging features of various entities that result in an enlarged retrocerebellar CSF space, such as inferior vermian hypoplasia (IVH) and several neurogenetic conditions.

Assessment of worst-case potential airborne asbestos exposure associated with the use of cosmetic talc: application of an exponential decay model.

Talc is used in cosmetic products to confer desirable properties, such as moisture absorption and smooth texture, to the finished products. Concerns have been raised about the potential presence of asbestos in products containing cosmetic talc. Reconstruction of potential asbestos exposure from the use of cosmetic talc products (assuming a trace level of asbestos) requires consideration of consumer use patterns. Although application generally only lasts seconds, exposure theoretically may continue if the consumer remains in the immediate vicinity. Most published exposure measurements have not adequately characterized the potential for continued exposure. In this analysis, estimates and measurements of airborne asbestos fiber concentrations associated with cosmetic talc use from 10 published studies were used as inputs to an exponential decay model to estimate "worst-case" exposure during and following application. The resulting geometric mean 30-min time-weighted average (TWA) concentrations were 0.006 f/cc for both puff and shaker application, for diapering, 0.0001 f/cc (adult applying baby powder) and 0.0002 f/cc (infant), and for makeup application, 0.0005 f/cc. Application of an exponential decay model to measured or estimated asbestos concentrations associated with the use of cosmetic talc products yields a conservative means to comprehensively reconstruct such exposures. Moreover, our results support that, if a cosmetic talc powder product contained a trace level of asbestos fibers, the "worst-case" airborne asbestos exposure associated with its application is low.

Non-Positive Experiences Encountered by Pupils During Participation in a Mindfulness-Informed School-Based Intervention.

Mindfulness-informed school-based mental health curricula show much promise in cultivating a positive school climate which supports the well-being and mental health of pupils and staff. However, non-positive pupil outcomes and experiences of school-based mental health interventions are often under-recognised and under-reported. This study sought to capture non-positive pupil experiences of a popular mindfulness-informed curriculum. Some pupils across all schools in the study described non-positive experiences, including having troubling thoughts and emotions, and not finding the programme effective. Contexts surrounding these experiences are explored and linked to existing literature, and subsequent recommendations for improvements are made, including the importance of having clear programme structure, definitions and aims, acknowledging and accommodating fidelity issues as best as possible, and better highlighting the potential for non-positive experiences and how they may be reduced.

Secondary School Athletic Trainers' Clinical Management Decisions of Low Socioeconomic Status Patients.

CONTEXT: Evidence suggests that negative social determinants of health (SDOH) and lower socioeconomic status (SES) contribute to health care disparities. Due to their accessibility in the high school setting, secondary school athletic trainers (SSATs) may encounter patients that are historically underserved in health care such as low SES patients. However, there is a significant gap in knowledge regarding how SES and SDOH may influence SSATs' clinical management decisions. OBJECTIVE: The purpose of this study was to describe SSATs' perceptions of how patient SDOH and SES influence clinical management decisions and to identify barriers to athletic healthcare. DESIGN: Cross-sectional study. SETTING: Online survey. PARTICIPANTS: NATA SSATs (6.7% response rate). MAIN OUTCOME MEASURE(S): SSATs were asked about their perceptions of patient SES and the SDOH (CVI = 0.83 for relevancy). Questions were ranked on a 4-point Liker scale on level of relevance and agreement. Data were summarized by means and standard deviations (SD), frequencies and proportions (%), and median scores. RESULTS: A total of 380 SSATs participated (years of experience mean=14.9±11.7 years). When providing care, most (71.3%) SSATs believed that their patient's health/health care access SDOH to be the most relevant of the 5 SDOH whereas the other 4 SDOH were less than 60% relevant. Most SSATs agreed/strongly agreed that patient SES impacts referral (67.4%) and the reliance on conservative treatment before referral (71.2%). SSATs identified patient/guardian compliance (70.2%) and type of health insurance (61.5%) as barriers to providing care to low SES patients. CONCLUSIONS: SSATs perceived health/health care access as the most relevant SDOH when providing care to low SES patients. When SSATs further considered the SES of patients, they identified all SDOHs as barriers to providing health care they were ill equipped to navigate as they delivered care and engaged in patient referral.

Validation of a shortened MR imaging protocol for pediatric spinal pathology.

OBJECTIVE: Conventional pediatric spine MRI protocols have multiple sequences resulting in long acquisition times. Sedation is consequently required. This study evaluates the diagnostic capability of a limited MRI spine protocol for selected common pediatric indications. METHODS: Spine MRIs at CHEO between 2017 and 2020 were reviewed across pediatric patients younger than four years old. Two blinded neuroradiologists reviewed limited scan sequences, and results were independently compared to previously reported findings from the complete imaging series. T2 sagittal sequences from the craniocervical junction to sacrum and T1 axial sequence of the lumbar spine constitute the short protocol, with the outcomes of interest being cerebellar ectopia, syrinx, level of conus, filum < 2 mm, fatty filum, and spinal dysraphism. RESULTS: A total of 105 studies were evaluated in 54 male and 51 female patients (mean age 19.2 months). The average combined scan time of the limited sequences was 15 min compared to 35 min for conventional protocols (delta = 20 min). The average percent agreement between full and limited sequences was > 95% in all but identifying a filum < 2 mm, where the percent agreement was 87%. Using limited MR sequences had high sensitivity (> 0.91) and specificity (> 0.99) for the detection of cerebellar ectopia, syrinx, fatty filum, and spinal dysraphism. CONCLUSION: This study demonstrates that selected spinal imaging sequences allow for consistent and accurate diagnosis of specific clinical conditions. A limited spine imaging protocol has potential as a screening test to reduce the need for full-sequence MRI scans. Further work is needed to determine utility of selected imaging for other clinical indications.

Reduced-order modeling and analysis of dynamic cerebral autoregulation via diffusion maps.

Objective.A data-driven technique for parsimonious modeling and analysis of dynamic cerebral autoregulation (DCA) is developed based on the concept of diffusion maps. Specifically, first, a state-space description of DCA dynamics is considered based on arterial blood pressure, cerebral blood flow velocity, and their time derivatives. Next, an eigenvalue analysis of the Markov matrix of a random walk on a graph over the dataset domain yields a low-dimensional representation of the intrinsic dynamics. Further dimension reduction is made possible by accounting only for the two most significant eigenvalues. The value of their ratio indicates whether the underlying system is governed by active or hypoactive dynamics, indicating healthy or impaired DCA function, respectively. We assessed the reliability of the technique by considering healthy individuals and patients with unilateral internal carotid artery (ICA) stenosis or occlusion. We computed the sensitivity of the technique to detect the presumed side-to-side difference in the DCA function of the second group (assuming hypoactive dynamics on the occluded or stenotic side), using McNemar's chi square test. The results were compared with transfer function analysis (TFA). The performance of the two methods was also compared under the assumption of missing data.Main results.Both diffusion maps and TFA suggested a physiological side-to-side difference in the DCA of ICA stenosis or occlusion patients with a sensitivity of 81% and 71%, respectively. Further, both two methods suggested the difference between the occluded or stenotic side and any two sides of the healthy group. However, the diffusion maps captured additional difference between the unoccluded side and the healthy group, that TFA did not. Furthermore, compared to TFA, diffusion maps exhibited superior performance when subject to missing data.Significance.The eigenvalues ratio derived using the diffusion maps technique can be potentially used as a reliable and robust biomarker for assessing how active the intrinsic dynamics of the autoregulation is and for indicating healthy versus impaired DCA function.

Anaesthesia for vascular emergencies - a state of the art review.

In this state-of-the-art review, we discuss the presenting symptoms and management strategies for vascular emergencies. Although vascular emergencies are best treated at a vascular surgical centre, patients may present to any emergency department and may require both immediate management and safe transport to a vascular centre. We describe the surgical and anaesthetic considerations for management of aortic dissection, aortic rupture, carotid endarterectomy, acute limb ischaemia and mesenteric ischaemia. Important issues to consider in aortic dissection are extent of the dissection and surgical need for bypasses in addition to endovascular repair. From an anaesthetist's perspective, aortic dissection requires infrastructure for massive transfusion, smooth management should an endovascular procedure require conversion to an open procedure, haemodynamic manipulation during stent deployment and prevention of spinal cord ischaemia. Principles in management of aortic rupture, whether open or endovascular treatment is chosen, include immediate transfer to a vascular care centre; minimising haemodynamic changes to reduce aortic shear stress; permissive hypotension in the pre-operative period; and initiation of massive transfusion protocol. Carotid endarterectomy for carotid stenosis is managed with general or regional techniques, and anaesthetists must be prepared to manage haemodynamic, neurological and airway issues peri-operatively. Acute limb ischaemia is a result of embolism, thrombosis, dissection or trauma, and may be treated with open repair or embolectomy, under either general or local anaesthesia. Due to hypercoagulability, there may be higher numbers of acutely ischaemic limbs among patients with COVID-19, which is important to consider in the current pandemic. Mesenteric ischaemia is a rare vascular emergency, but it is challenging to diagnose and associated with high morbidity and mortality. Several peri-operative issues are common to all vascular emergencies: acute renal injury; management of transfusion; need for heparinisation and reversal; and challenging postoperative care. Finally, the important development of endovascular techniques for repair in many vascular emergencies has improved care, and the availability of transoesophageal echocardiography has improved monitoring as well as aids in surgical placement of endovascular grafts and for post-procedural evaluation.

Point-of-care ultrasound use in emergencies: what every anaesthetist should know.

Point-of-care ultrasound has been embraced by anaesthetists as an invaluable tool for rapid diagnosis of haemodynamic instability, to ensure procedural safety and monitor response to treatments. Increasingly available, affordable and portable, with emerging evidence of improved patient outcomes, point-of-care ultrasound has become a valuable tool in the emergency setting. This state-of-the-art review describes the feasibility of point-of-care ultrasound practice, training and maintenance of competence. It also describes the many uses of point-of-care ultrasound for the anaesthetist and describes the most salient point-of-care ultrasound views for anaesthetic emergencies including: undifferentiated shock; hypoxemia; and trauma. Procedural safety is also discussed in addition to relevant important governance aspects. Cardiac function should be assessed using the parasternal long axis, parasternal short basal/mid-papillary/apical, apical four chamber and subcostal four chamber views, and should include a visual estimation of global left ventricular ejection fraction. Other cardiovascular conditions that can be identified using point-of-care ultrasound include: pericardial effusion; cardiac tamponade; and pulmonary embolism. Pulmonary emergency conditions that can be diagnosed using point-of-care ultrasound include pneumothorax; pleural effusion; and interstitial syndrome. The extended focused assessment with sonography for trauma examination may of value in patients who are hypotensive in order to identify intra-abdominal haemorrhage, pneumothoraces and haemothoraces.

Impact of 10-Day Fulbright Specialist Program and Project Pink Blue Education Sessions on Medical Oncology Knowledge Among Physicians Who Treat Cancer in Nigeria.

Despite an estimated population of over 201 million and over 115,950 yearly diagnosed new cases of cancer, Nigeria does not have dedicated medical oncologists. Most oncology care is delivered through surgical and clinical oncologists, who are trained in both radiation and medical oncology and they number fewer than 50 in the country. With a limited number of oncology professionals, cancer patients in Nigeria experience poor health outcomes, with an estimated cancer mortality rate of 75,000 deaths per year. Participants from 15 Nigerian states were selected to attend the medical oncology training. Through the support of Fulbright Specialist Program and Project PINK BLUE, two of the authors delivered 10 days of lectures based on ASCO, ESMO, and NCCN guidelines. Mean scores of both the pre- and post-course tests as well as a 1-year follow-up test were compared using GraphPad Prism 7.0a by paired t-tests. Forty-four clinical oncologists were selected for participation. Twenty-five (57%) completed the pre- and post-course tests. Of the 25 that completed both tests, percentage of correct answers increased from 45 to 59% (2-sided p-value < 0.0001). Improvements were seen in attending doctors 45 to 59% (p = 0.0046) and resident doctors 45 to 59% (0.0007). Eleven doctors responded to the 1-year follow-up test. Although not statistically significant, a numerical pattern for the benefits was maintained 1 year after the program (45% pre-course versus 52% post-course correct answers, Fisher's exact, p = 0.4185). In the short term, the training improved medical oncology knowledge in Nigeria, regardless of the participant's carrier stage. Long-term benefits were not sustained in a small sample of participants, and continuing education strategies are necessary. Similar models may be employed across Africa.

Changing Parental Knowledge and Treatment Acceptance for ADHD: A Pilot Study.

This pilot study assessed the feasibility and potential effectiveness of a single-session workshop in modifying parental beliefs/knowledge about attention-deficit/hyperactivity disorder (ADHD) in children and impact on treatment acceptance/utilization. Concerns raised by school professionals about lack of treatment follow-through after ADHD diagnosis and parental misinformation about medication usage catalyzed this project. A single-group pre-post quasi-experimental design was used. Sixty-eight parents completed ADHD knowledge/belief scales and stress inventories, and pre-ADHD and post-ADHD information workshop. Follow-up calls were made after the workshop to assess treatment utilization. Parents/caregivers experienced significant knowledge and belief changes regarding medication efficacy, willingness to accept physician treatment recommendations, and rejection of non-empirically based treatments. Follow-up data showed that 41% of contacted participants met with physicians to discuss medication utilization and behavioral treatments. Brief, one-session psycho-educational workshops were feasible and impacted parental beliefs and behaviors regarding scientifically supported interventions for ADHD.

American Speech-Language-Hearing Association Clinical Practice Guideline: Cognitive Rehabilitation for the Management of Cognitive Dysfunction Associated With Acquired Brain Injury.

BACKGROUND: Cognitive-communication impairments following acquired brain injury (ABI) can have devastating effects on a person's ability to participate in community, social, vocational, and academic preinjury roles and responsibilities. Guidelines for evidence-based practices are needed to assist speech-language pathologists (SLPs) and other rehabilitation specialists in the delivery of cognitive rehabilitation for the adult population. PURPOSE: The American Speech-Language-Hearing Association, in conjunction with a multidisciplinary panel of subject matter experts, developed this guideline to identify best practice recommendations for the delivery of cognitive rehabilitation to adults with cognitive dysfunction associated with ABI. METHOD: A multidisciplinary panel identified 19 critical questions to be addressed in the guideline. Literature published between 1980 and 2020 was identified based on a set of a priori inclusion/exclusion criteria, and main findings were pooled and organized into summary of findings tables. Following the principles of the Grading of Recommendations Assessment, Development and Evaluation Evidence to Decision Framework, the panel drafted recommendations, when appropriate, based on the findings, overall quality of the evidence, balance of benefits and harms, patient preferences, resource implications, and the feasibility and acceptability of cognitive rehabilitation. RECOMMENDATIONS: This guideline includes one overarching evidence-based recommendation that addresses the management of cognitive dysfunction following ABI and 11 subsequent recommendations focusing on cognitive rehabilitation treatment approaches, methods, and manner of delivery. In addition, this guideline includes an overarching consensus-based recommendation and seven additional consensus recommendations highlighting the role of the SLP in the screening, assessment, and treatment of adults with cognitive dysfunction associated with ABI. Future research considerations are also discussed.

A Pt(IV)-conjugated brain penetrant macrocyclic peptide shows pre-clinical efficacy in glioblastoma.

Glioblastoma (GBM) is the most aggressive primary malignant brain tumor, with a median survival of approximately 15 months. Treatment is limited by the blood-brain barrier (BBB) which restricts the passage of most drugs to the brain. We previously reported the design and synthesis of a BBB-penetrant macrocyclic cell-penetrating peptide conjugate (M13) covalently linked at the axial position of a Pt(IV) cisplatin prodrug. Here we show the Pt(IV)-M13 conjugate releases active cisplatin upon intracellular reduction and effects potent in vitro GBM cell killing. Pt(IV)-M13 significantly increased platinum uptake in an in vitro BBB spheroid model and intravenous administration of Pt(IV)-M13 in GBM tumor-bearing mice led to higher platinum levels in brain tissue and intratumorally compared with cisplatin. Pt(IV)-M13 administration was tolerated in naïve nude mice at higher dosage regimes than cisplatin and significantly extended survival above controls in a murine GBM xenograft model (median survival 33 days for Pt(IV)-M13 vs 24 days for Pt(IV) prodrug, 22.5 days for cisplatin and 22 days for control). Increased numbers of γH2AX nuclear foci, biomarkers of DNA damage, were observed in tumors of Pt(IV)-M13-treated mice, consistent with elevated platinum levels. The present work provides the first demonstration that systemic injection of a Pt(IV) complex conjugated to a brain-penetrant macrocyclic peptide can lead to increased platinum levels in the brain and extend survival in mouse GBM models, supporting further development of this approach and the utility of brain-penetrating macrocyclic peptide conjugates for delivering non-BBB penetrant drugs to the central nervous system.

Evaluation of volatile organic compound (VOC) emissions from memory foam mattresses and potential implications for consumer health risk.

Chemical emissions from two new memory foam mattresses were evaluated in a simulated consumer use environment over the course of 32 days. Passive 12- and 24-h samples (n = 62) were collected for various VOCs. Airborne concentrations of chemicals associated with the mattresses (2-propanol, acetone, chloromethane, toluene, and ΣVOC) peaked during the first day after installation and progressively decayed over the course of the following 31 days. Emission rates were derived using a two-phase, double exponential source decay model paired with a one-compartment generalized indoor air quality model; short- and long-term emission half-lives for individual chemicals were on the order of hours (approximately 4 or 12 h) and days (approximately 24 days), respectively. Model-estimated average ΣVOC concentrations for the 32-day period of the study were approximately 20 and 33 µg/m3 for Mattress 1 and 2, respectively, while the modeled one-year average concentrations were 2.7 and 4.2 µg/m3, respectively. First-year trends for both mattresses were qualitatively similar, with the sum of 2-propanol, acetone, chloromethane, and toluene contributing to approximately 81% and 95% of the first-year ΣVOC concentration of Mattress 1 and 2, respectively. The airborne concentrations of individual chemicals and ΣVOC measured and modeled in this study were well below available health-based benchmarks for individual chemicals and within available indoor air quality recommendations for ΣVOC, suggesting that it is unlikely that the use of the models of mattresses evaluated in this study would pose a health risk to consumers.

OPTN/SRTR 2020 Annual Data Report: Lung.

For the first time in a decade, both the number of candidates added to the waiting list and the number of lung transplants performed decreased from the year prior; the number of lung donors also declined. This slowing of transplant activities in 2020 was associated with a modest increase in waitlist mortality. The year 2020 was notable for the global outbreak of the COVID-19 pandemic, which undoubtedly influenced all trends noted in lung transplantation. Time to transplant continued to decrease, with a median time to transplant of 1.4 months across all waitlist candidates. Posttransplant survival remained stable, with 89.4% of transplant recipients surviving to 1 year, 74.8% to 3 years, and 61.2% to 5 years.

Updated profiles of everyday executive function in youth with Down syndrome using the BRIEF-2.

BACKGROUND: Executive function difficulties in youth with Down syndrome (DS) are well recognised using informant-report measures. However, the profile of relative challenges and strengths has not yet been evaluated using the Behavior Rating Inventory of Executive Function, Second Edition (BRIEF-2), which includes a new internal factor structure. METHOD: Using the BRIEF-2, profiles of everyday parent-reported executive function (EF) were evaluated in youth with DS (n = 34) and compared with age-based and sex-based norms. EF profiles were also compared across raters (parent vs. teacher, n = 20) and relative to mental age-matched typically developing controls (ns = 19 in each group). RESULTS: Although within-group differences were not revealed on indexes, significant differences were found among BRIEF-2 scales. Across raters, teachers reported significantly more difficulties than parents. Compared with mental age-matched typically developing controls, the DS group was rated more poorly on some but not all BRIEF-2 scales. CONCLUSIONS: At the scale, but not the index level, the BRIEF-2 identifies a variegated EF profile in children with DS. For several of the scales, significant differences were noted relative to both chronological age expectations (using norms) and mental-age expectations (using a developmentally matched comparison group). At the scale level, the BRIEF-2 continues to be a sensitive tool for identifying executive function difficulties as well as profiles of relative strengths and weaknesses in children with DS.

Cardiometabolic health after first pregnancy: Associations with social determinants of health. A nuMoM2b-HHS study.

Study objective: This study sought to evaluate the associations between social determinants of health (SDOH) at the time of first pregnancy and subsequent cardiometabolic health, defined as the development of metabolic syndrome. Design: nuMoM2b-HHS (Nulliparous Pregnancy Outcomes Study- Monitoring Mothers-to-Be-Heart Health Study) is an ongoing prospective cohort study. Setting: Eight academic medical centers enrolled and continue to follow participants. Participants: 4484 participants followed a mean of 3.2 years from the time of their first pregnancy. Interventions: N/a. Main outcome measure: Unadjusted and adjusted Poisson regression models with robust standard errors were used to obtain relative risks and 95% confidence intervals estimating the risk of metabolic syndrome for each baseline SDOH. In secondary analyses we examined the associations between SDOH and incident hypertension, obesity, and diabetes mellitus. Results: Metabolic syndrome developed in 13.6% of participants. Higher socioeconomic position at the time of pregnancy was associated with lower rates of metabolic syndrome [income > 200% poverty level aRR 0.55 (95% CI, 0.42-0.71), attainment of a bachelor's degree aRR 0.62 (0.46-0.84) or higher aRR 0.50 (0.35-0.71)], while being single [aRR 1.45 (95% CI, 1.18-1.77)] and having low health literacy were associated with a greater risk of metabolic syndrome [aRR 1.98 (95% CI, 1.28-3.07)]. Conclusions: Over a short interval following first pregnancy, participants accumulated high proportions of cardiovascular risk factors and metabolic syndrome, with some risk associated with SDOH. The impact of interventions addressing SDOH in pregnant people on cardiometabolic health should be tested as a means of reducing health inequities at the population level.

Integrative sequencing discovers an ATF1-motif enriched molecular signature that differentiates hyalinizing clear cell carcinoma from mucoepidemoid carcinoma.

OBJECTIVES: Salivary gland tumors are comprised of a diverse group of malignancies with widely varying prognoses. These cancers can be difficult to differentiate, especially in cases with limited potential for immunohistochemistry (IHC)-based characterization. Here, we sought to define the molecular profile of a rare salivary gland cancer called hyalinizing clear cell carcinoma (HCCC), and identify a molecular gene signature capable of distinguishing between HCCC and the histopathologically similar disease, mucoepidermoid carcinoma (MEC). MATERIALS AND METHODS: We performed the first integrated full characterization of five independent HCCC cases. RESULTS: We discovered insulin-like growth factor alterations and aberrant IGF2 and/or IGF1R expression in HCCC tumors, suggesting a potential dependence on this pathway. Further, we identified a 354 gene signature that differentiated HCCC from MEC, and was significantly enriched for genes with an ATF1 binding motif in their promoters, supporting a transcriptional pathogenic mechanism of the characteristic EWSR1-ATF1 fusion found in these tumors. Of the differentially expressed genes, IGF1R, SGK1 and SGK3 were found to be elevated in the HCCCs relative to MECs. Finally, analysis of immune checkpoints and subsequent IHC demonstrated that CXCR4 protein was elevated in several of the HCCC cases. CONCLUSION: Collectively, our data identify an ATF1-motif enriched gene signature that may have clinical utility for molecular differentiation of HCCCs from other salivary gland tumors and discover potential actionable alterations that may benefit the clinical care of recurrent HCCC patients.

OPTN/SRTR 2019 Annual Data Report: Lung.

The number of lung transplants performed continues to increase annually and reached an all-time high in 2019, with decreasing waitlist mortality. These trends are attributable to an increasing number of candidates listed for transplant each year and a continuing increase in the number of donors. Despite these favorable trends, 6.4% of lungs recovered for transplant were not transplanted in 2019, and strategies to optimize use of these available organs may reduce the number of waitlist even further. Time to transplant continued to decrease, as over 50% of candidates waited 3 months or less in 2019, yet regional heterogeneity remained despite policy changes intended to improve allocation equity. Small gains continued in posttransplant survival, with 1-year survival at 88.8%; 3 year, 74.4%; 5 year, 59.2%, and 10 year, 33.1 %.