In situ microwave fixation provides an instantaneous snapshot of the brain metabolome.

Brain glucose metabolism is highly heterogeneous among brain regions and continues postmortem. In particular, we demonstrate exhaustion of glycogen and glucose and an increase in lactate production during conventional rapid brain resection and preservation by liquid nitrogen. In contrast, we show that these postmortem changes are not observed with simultaneous animal sacrifice and in situ fixation with focused, high-power microwave. We further employ microwave fixation to define brain glucose metabolism in the mouse model of streptozotocin-induced type 1 diabetes. Using both total pool and isotope tracing analyses, we identified global glucose hypometabolism in multiple brain regions, evidenced by reduced 13C enrichment into glycogen, glycolysis, and the tricarboxylic acid (TCA) cycle. Reduced glucose metabolism correlated with a marked decrease in GLUT2 expression and several metabolic enzymes in unique brain regions. In conclusion, our study supports the incorporation of microwave fixation for more accurate studies of brain metabolism in rodent models.

Evaluating the Efficiency and Equity of Autism Diagnoses via Telehealth During COVID-19.

Given existing barriers to a timely autism diagnosis, this study compares the efficiency and equity of diagnoses conducted in-person vs. telehealth in a developmental behavioral pediatrics setting. The transition to telehealth was prompted by the COVID-19 pandemic. Eleven months of clinic data in electronic medical records were retrospectively analyzed for children diagnosed with autism in-person (N = 71) vs. telehealth (N = 45). Time to autism diagnosis, patient demographics, and deferred diagnoses did not significantly differ across visit types. However, privately insured patients and families living farther from the clinic had a longer time to diagnosis via telehealth vs. in-person. Results of this exploratory study highlight the feasibility of telehealth evaluations for autism and which families may benefit from additional support to ensure a timely diagnosis.

Improving Efficiency and Equity in Early Autism Evaluations: The (S)TAAR Model.

This paper describes the (Sin Exclusión) Transdisciplinary Autism Assessment and Resources ([S]TAAR) model and presents early metrics tracking efficiency and equity in access to high-quality comprehensive autism evaluations for young children. Retrospective chart reviews over one year (08/2018-08/2019) with n = 173 children were reviewed. Through care coordination with community providers, the model was developed to meet local needs by increasing throughput of children (< 4 years old) evaluated by a transdisciplinary team. Team-based processes included pre-visit triage, synchronous evaluation procedures, case conferencing, huddles, and care coordination. The model led to increased patient throughput, reductions in waitlist and time to diagnosis, and improved provider satisfaction. Improvements in access to care were equitable across patient race, ethnicity, language, and insurance type.

Extending Expectancy Theory to Food Intake: Effect of a Simulated Fast-Food Restaurant on Highly and Minimally Processed Food Expectancies.

Unhealthy diets are widespread and linked to a number of detrimental clinical outcomes. The current preregistered experiment extended Expectancy Theory into the study of food intake; specifically, we tested whether a fast-food restaurant affects food expectancies, or the emotions one expects to feel while eating highly (e.g., pizza) and minimally (e.g., carrots) processed foods. Participants (N = 200, M age = 18.79) entered a simulated fast-food restaurant or a neutral space, completed questionnaires, and engaged in a 'bogus' taste test. The simulated fast-food restaurant increased positive highly-processed food expectancies (d = 0.29). Palatable eating coping motives scores did not moderate the effect; however, this clinically-relevant pattern of eating behavior was associated with greater positive highly-processed food expectancies. In addition, there was an indirect effect of the fast-food restaurant on ad libitum food intake through positive highly-processed food expectancies. Reducing positive highly-processed food expectancies may improve diet, which may broadly impact health.

Bridging Radiation Therapy Before Commercial Chimeric Antigen Receptor T-Cell Therapy for Relapsed or Refractory Aggressive B-Cell Lymphoma.

PURPOSE: CD19-targeting chimeric antigen receptor T-cell (CART) therapy has emerged as a promising treatment for relapsed/refractory aggressive B-cell lymphoma (r/rABL), culminating in 2 US Food and Drug Administration-approved therapies: tisagenlecleucel (tisa-cel) and axicabtagene ciloleucel (axi-cel). Following leukapheresis and in preparation for CART infusion, contemporary bridging and lymphodepletion regimens rely mostly on cytotoxic chemotherapy. Here, in a cohort of patients treated with commercial tisa-cel and axi-cel, we show that bridging-RT may offer a supplemental approach. METHODS AND MATERIALS: Thirty-one patients receiving commercial tisa-cel (n = 13) or axi-cel (n = 18) between August 2018 and February 2019 for r/rABL were retrospectively reviewed. Patients were categorized into 2 groups: (1) bridging-RT within 30 days of CART infusion or (2) nonbridging-RT (NBRT), in which patients received either remote RT greater than 30 days before CART infusion or no prior RT. RESULTS: Five patients received bridging-RT within 30 days of CART infusion. Median bridging-RT dose was 37.5 Gy and was completed a median of 13 days before infusion. No grade 3 (G3) or higher RT-toxicities occurred. No patients in the bridging-RT group experienced G3 or higher CART-related toxicities (CRS or neurotoxicity), and 23% (n = 6) and 15% (n = 4) experienced G3-5 CRS and G3-5 neurotoxicity in the NBRT group, respectively. Overall treatment response in the bridging-RT and NBRT groups was 80% and 64%, respectively. The axi-cel CART product was associated with CRS (odds ratio [OR] = 26.67, P = .001) and CRS correlated with neurotoxicity (OR = 12.22, P = .028). There was a trend toward an association for CRS with metabolic tumor volume (OR = 1.06/mL, P = .141) and TLG (OR = 1.01/mL x standard uptake value, P = .099). CONCLUSIONS: Bridging-RT before commercial CART does not appear to increase the risk for CART-related toxicities or negatively affect outcomes in r/rABL patients. No G3 or higher RT-toxicities occurred in this series. Pretreatment metabolic tumor burden may be associated with CART-associated CRS; however, larger patient numbers are required to elucidate significant associations. Future work to prospectively assess the value of bridging-RT is warranted.

Evaluating the Impact of Treatment Care Planning on Quality Measures.

PURPOSE: The Center for Medicare & Medicaid Innovation Oncology Care Model (OCM) requires documentation of a 13-point Institute of Medicine care management plan for Medicare patients. In addition, OCM includes evaluation of quality using key performance measures that align with the ASCO Quality Oncology Practice Initiative (QOPI). Both efforts are designed to improve patient-centered care and foster patients' engagement in their care plan. METHODS: A multicenter quality improvement project was conducted to develop a strategy to meet the OCM treatment planning (TP) requirement (Plan), pilot clinician education coupled with use of electronic TP in early-stage breast cancer (Do), evaluate the impact of TP on QOPI measures (Study), and develop recommendations for future implementation (Act). RESULTS: Thirty-three clinical providers and 171 women with breast cancer were included. Improved performance on several QOPI measures was observed for the intervention group compared with the historical control group. CONCLUSION: Meeting the OCM TP requirement through incorporating a technology solution provided an opportunity for quality improvement and preparation for full-scale TP within the OCM. TP delivery was associated with improved performance on select ASCO QOPI measures, which is likely to correspond with improved performance on quality measures within OCM.

Healthcare utilization, Medicare spending, and sources of patient distress identified during implementation of a lay navigation program for older patients with breast cancer.

PURPOSE: Despite benefits for patients, sustainability of breast cancer navigation programs is challenging due to the lack of reimbursement for navigators. This analysis describes distress reported by breast cancer patients to navigators and the impact of navigation on healthcare utilization for older adults with breast cancer. METHODS: We conducted a retrospective cohort study of Medicare administrative claims data and patient-reported distress assessments. The primary outcome was Medicare spending per beneficiary per quarter. Secondary outcomes included (1) the number of hospitalizations or ER visits in each quarter; (2) distress levels; and (3) causes of distress reported by patients to their navigators. A subset analysis was conducted for stage I/II/III versus stage IV patients. RESULTS: 776 navigated and 776 control patients were included in the analysis. The average age at diagnosis was 74 years; 13% of the subjects were African American; 95% of patients had stage I-III. Medicare spending declined faster for the navigated group than the matched comparison group by $528 per quarter per patient (95% CL -$667, -$388). Stage I/II/III navigated patients showed a statistically significant decline in Medicare spending, ER visits, and hospitalizations over time compared to the matched comparison group. No differences were observed for stage IV patients. Eighteen percent of patients reported moderate distress. Informational and physical distress were more common in late stage than in early-stage breast cancer. CONCLUSIONS: Lay navigation reduced healthcare utilization in older adults with breast cancer, with the greatest impact observed in early-stage breast cancer patients.

Effect of slice excitation profile on ungated steady state cardiac perfusion imaging.

In cardiac perfusion imaging, choice of flip angle is an important factor for steady state acquisition. This work focuses on presenting an analytical framework for understanding how non-ideal slice excitation profiles affect contrast in ungated 2D steady state cardiac perfusion studies, and to study a technique for estimating flip angle that maximizes enhanced/unenhanced myocardial contrast-to-noise ratio (CNR) in single slice and multi-slice acquisitions. A numerical simulation of ungated 2D golden ratio radial spoiled gradient echo (SPGR) was created that takes into consideration the actual (Bloch simulated) slice excitation profile. The effect of slice excitation profile on myocardial CNR as a function of flip angle was assessed in phantoms and in-vivo. For fast RF pulses, the flip angle that yields maximum CNR (considering the actual slice excitation profile) was considerably higher than expected, assuming an ideal excitation. The simulation framework presented accurately predicts the flip angle yielding maximum CNR when the actual slice excitation profile is taken into consideration. The prescribed flip angle for optimal contrast in ungated 2D steady-state SPGR cardiac perfusion studies can vary significantly from that calculated when an ideal slice excitation profile is assumed. Consideration of the actual slice excitation can yield a more optimal flip angle estimate in both the single slice and multi-slice cases.

Transcatheter Aortic Valve Implantation - Yesterday, Today and Tomorrow.

Since the first transcatheter aortic valve implantation (TAVI) was performed by Alain Cribier and colleagues in 2002 [1], the technology has garnered global support with more than 200,000 devices implanted. The rapid adoption of this technology has been driven by the need for a less invasive treatment modality in a cohort of patients often denied conventional surgical valve replacement due to an unacceptably high perioperative risk, whether real or perceived [2]. This, together with evidence that the technology confers morbidity and mortality advantages compared to medical therapy [3,4] and at least equivalent outcomes to surgical valve replacement [5,6] in select cohorts, has seen clinical approval in more than 50 countries. The last 13 years has seen an evolution of practises and equipment affecting almost every aspect of the TAVI procedure from pre-procedural assessment to device design and post-procedural care. The almost exponential rate of change has both benefits and risks. Benefits, in that impactful changes are translated into clinical practice very rapidly, but risks, in that meaningful comparative research studies potentially lag behind and can be outmoded by the time they are published. This instability may in turn delay regulatory review and approval processes that are based on such studies. The aim of this review is to provide an overview of the evolution of TAVI, its current clinical position and likely future directions.

Macrophage Migration Inhibitory Factor Is Detrimental in Pneumococcal Pneumonia and a Target for Therapeutic Immunomodulation.

Mortality from pneumococcal pneumonia remains high despite antibiotic therapy, highlighting the pathogenic potential for host inflammation. We demonstrate that macrophage migration inhibitory factor (MIF), an innate immune mediator, is detrimental for survival and associated with lung pathology, inflammatory cellular infiltration, and bacterial replication in a mouse model of pneumococcal pneumonia, despite being necessary for clearance from the nasopharynx. Treatment of animals with a small-molecule inhibitor of MIF improves survival by reducing inflammation and improving bacterial control. Our work demonstrates that MIF modulates beneficial versus detrimental inflammatory responses in the host-pneumococcal interaction and is a potential target for therapeutic modulation.

The significance of pre-arrest factors in out-of-hospital cardiac arrests witnessed by emergency medical services: a report from the Victorian Ambulance Cardiac Arrest Registry.

BACKGROUND: The significance of pre-arrest factors in out-of-hospital cardiac arrests (OHCA) witnessed by emergency medical services (EMS) is not well established. The purpose of this study was to assess the association between prodromal symptoms and pre-arrest clinical observations on the arresting rhythm and survival in EMS witnessed OHCA. METHODS: Between 1st January 2003 and 31st December 2011, 1056 adult EMS witnessed arrests of a presumed cardiac aetiology were identified from the Victorian Ambulance Cardiac Arrest Registry. Pre-arrest prodromal features and clinical characteristics were extracted from the patient care record. Backward elimination logistic regression was used to identify pre-arrest factors associated with an initial shockable rhythm and survival to hospital discharge. RESULTS: The median age was 73.0 years, 690 (65.3%) were male, and the rhythm of arrest was shockable in 465 (44.0%) cases. The most commonly reported prodromal symptoms prior to arrest were chest pain (48.8%), dyspnoea (41.8%) and altered consciousness (37.8%). An unrecordable systolic blood pressure was observed in 34.4%, a respiratory rate <13 or >24min(-1) was present in 43.1%, and 45.5% had a Glasgow coma score <15. In the multivariable analysis, the following pre-arrest factors were significantly associated with survival: age, public location, aged care facility, chest pain, arm or shoulder pain, dyspnoea, dizziness, vomiting, ventricular tachycardia, pulse rate, systolic blood pressure, respiratory rate, Glasgow coma score, aspirin and inotrope administration. CONCLUSION: Pre-arrest factors are strongly associated with the arresting rhythm and survival following EMS witnessed OHCA. Potential opportunities to improve outcomes exist by way of early recognition and management of patients at risk of OHCA.

Macrophage migration inhibitory factor promotes clearance of pneumococcal colonization.

Human genetic polymorphisms associated with decreased expression of macrophage migration inhibitory factor (MIF) have been linked to the risk of community-acquired pneumonia. Because Streptococcus pneumoniae is the leading cause of community-acquired pneumonia and nasal carriage is a precursor to invasive disease, we explored the role of MIF in the clearance of pneumococcal colonization in a mouse model. MIF-deficient mice (Mif(-/-)) showed prolonged colonization with both avirulent (23F) and virulent (6A) pneumococcal serotypes compared with wild-type animals. Pneumococcal carriage led to both local upregulation of MIF expression and systemic increase of the cytokine. Delayed clearance in the Mif(-/-) mice was correlated with reduced numbers of macrophages in upper respiratory tract lavages as well as impaired upregulation of MCP-1/CCL2. We found that primary human monocyte-derived macrophages as well as THP-1 macrophages produced MIF upon pneumococcal infection in a pneumolysin-dependent manner. Pneumolysin-induced MIF production required its pore-forming activity and phosphorylation of p38-MAPK in macrophages, with sustained p38-MAPK phosphorylation abrogated in the setting of MIF deficiency. Challenge with pneumolysin-deficient bacteria demonstrated reduced MIF upregulation, decreased numbers of macrophages in the nasopharynx, and less effective clearance. Mif(-/-) mice also showed reduced Ab response to pneumococcal colonization and impaired ability to clear secondary carriage. Finally, local administration of MIF was able to restore bacterial clearance and macrophage accumulation in Mif(-/-) mice. Our work suggests that MIF is important for innate and adaptive immunity to pneumococcal colonization and could be a contributing factor in genetic differences in pneumococcal disease susceptibility.

Direction of first bystander call for help is associated with outcome from out-of-hospital cardiac arrest.

BACKGROUND: Preventable bystander delays following out-of-hospital cardiac arrest (OHCA) are common, and include bystanders inappropriately directing their calls for help. METHODS: We retrospectively extracted Utstein-style data from the Victorian Ambulance Cardiac Arrest Registry (VACAR) for adult OHCA occurring in Victoria, Australia, between July 2002 and June 2012. Emergency medical service (EMS) witnessed events were excluded. Cases were assigned into two groups on the basis of the first bystander call for help being directed to EMS. Study outcomes were: likelihood of receiving EMS treatment; survival to hospital, and; survival to hospital discharge. RESULTS: A total of 44499 adult OHCA cases attended by EMS were identified, of which first bystander calls for help were not directed to EMS in 2842 (6.4%) cases. Calls to a relative, friend or neighbour accounted for almost 60% of the total emergency call delays. Patient characteristics and survival outcomes were consistently less favourable when calls were directed to others. First bystander call to others was independently associated with older age, male gender, arrest in private location, and arrest in a rural region. The risk-adjusted odds of treatment by EMS (OR 1.33, 95% CI 1.20-1.48), survival to hospital (OR 1.64, 95% CI 1.37-1.96) and survival to hospital discharge (OR 1.64, 95% CI 1.13-2.36) were significantly improved if bystanders called EMS first. CONCLUSION: The frequency of inappropriate bystander calls following OHCA was low, but associated with a reduced likelihood of treatment by EMS and poorer survival outcomes.

The SADRA Lotus Valve System: a fully repositionable, retrievable prosthesis.

Transcatheter aortic valve implantation (TAVI) has become the preferred treatment option for patients with severe aortic stenosis at extreme surgical risk and an acceptable alternative to surgical aortic valve replacement in patients at high risk. Despite a growing amount of evidence in support of TAVI there remain important limitations and recognized complications. The SADRA Lotus Valve System is a novel TAVI device capable of allowing full repositionability and retrievability, which may address some of the first generation limitations.

The design and rationale of the Australian Cooperative National Registry of Acute Coronary care, Guideline Adherence and Clinical Events (CONCORDANCE).

BACKGROUND: Cardiovascular observational registries characterise patients and describe the manner and use of therapeutic strategies. They facilitate analyses on the quality of care among participating institutions and document variations in clinical practice which can be benchmarked against best practice recommendations. The Cooperative National Registry of Acute Coronary care, Guideline Adherence and Clinical Events (CONCORDANCE) is an Australian observational registry that describes management and outcomes in patients with acute coronary syndromes (ACS) and feeds back both performance and outcome measures to participating hospitals. METHODS: The CONCORDANCE registry has been designed within a comparative effectiveness research (CER) framework to collect and report data from hospitals located in geographically diverse regions of Australia. Information including patient demographics, presenting characteristics, past medical history, in-hospital management and outcomes at six months and two years are entered into a web-based database using an electronic clinical record form (eCRF). Individual hospital information is returned to the sites in a real time confidential report detailing information on key performance indicator (KPI) process measures and outcomes benchmarked against the aggregated study cohort. Governance rules ensure data security and protect patient and clinician confidentiality. Consistent with a CER framework, additional characteristics of the registry include: (a) the capacity to evaluate associations between the inter and intra hospital systems and the provision of evidence based care and outcomes, (b) ongoing data collection from representative hospitals which allow spatial and temporal analysis of change in practice and the application of treatment modalities in the real world setting and (c) the provision of a data spine for quality improvement strategies and practical clinical trials. CONCLUSION: The CONCORDANCE registry is a clinician-driven initiative describing clinical care for ACS patients admitted to Australian hospitals. The registry generates high quality data which is fed back to clinicians, and key stakeholders in ACS care. Using a CER approach, the registry describes the translation of randomised trial evidence into practice, and provides insights into strategies that could improve care and ultimately patient outcomes.

New DES: a new step forward?

Despite the benefits of first generation drug eluting stents (DES), concerns have been raised over their long term safety in particular the risk of stent thrombosis. As a result, the current generation and novel DES have been developed, the latter includes DES with biocompatible and biodegradable polymers, polymer free DES and completely bioresorbable stent platforms. Many of these stents are currently under evaluation in clinical trials, and early results are promising. This paper reviews the progress thus far in DES technology and aims to highlight the impact of recent DES innovations on clinical efficacy and safety.

RapidChek SELECT Salmonella enteritidis test system for the detection of Salmonella enteritidis in poultry house drag swabs, shell egg pools, and chicken carcass rinsates.

The RapidChek SELECT Salmonella Enteritidis Test System was validated for the detection of Salmonella Enteritidis (SE) in poultry house drag swabs, shell egg pools, and chicken carcass rinsates. The method utilizes RapidChek SELECT Salmonella (AOAC PTM License No. 080601) proprietary primary and secondary enrichment media. Following enrichment, an immunochromatographic test strip is inserted into the tube containing the secondary enrichment broth, developed for 10 min, and interpreted. Salmonella Enteritidis-inoculated samples (1-5 CFU SE/analytical unit) were tested by the test method as well as the appropriate cultural reference method U.S. Food and Drug Administration-Bacteriological Analytical Manual (drag swabs and egg pools) or U.S. Department of Agriculture-Food Safety and Inspection Service (chicken carcass rinsates). A total of 80 samples were tested by both methods in the study. Fifty-two samples were positive by the RapidChek SELECT Salmonella Enteritidis method and 38 were found positive by the respective reference method. The sensitivity of the method was 100% and the specificity was 100%. The accuracy of the test method was 137%, indicating that the method was more sensitive than the reference method. The RapidChek SELECT Salmonella Enteritidis method was tested with 82 Salmonella Group D1 strains including 63 Salmonella Enteritidis strains as well as 32 non-Salmonella Group D1 strains representing 10 bacteria genera. The test method detected all 82 Group D1 strains (100% sensitivity). None of the non-Salmonella Group D1 or other genera of bacteria were detected, indicating a specificity of 100%. The method was shown to be highly robust and stable under control and accelerated stability conditions.

Spontaneous coronary artery dissection in a female with antiphospholipid syndrome.

We report a case of spontaneous coronary artery dissection occurring in a young female who had been diagnosed with antiphospholipid syndrome. Coronary angiography revealed extensive dissection in the proximal to mid LAD. She was treated conservatively with an excellent result. Follow-up coronary angiography at two months failed to reveal any evidence of the previous dissection.