Designing Porous Ion Emitters for Thermal Ionization Mass Spectrometry: Evaluating Metal-Organic Frameworks.

This work describes the first exploration of metal-organic frameworks (MOFs) as "next-generation" ion emitters for thermal ionization mass spectrometry (TIMS). MOFs were identified as promising candidates for this application given the synthetic control over their desired structural properties. This tunability results in well-ordered, high-surface-area, high-porosity frameworks with targeted sorption affinities. Here, we explored an aluminum-based, bipyridine-containing MOF (MOF-253) with and without incorporating a high work function metal, rhenium (Re). After analysis of an Nd-bearing MOF, we hypothesized that the well-dispersed, sponge-like interconnected network of the degraded structure would enhance Nd ionization more than traditional TIMS loading techniques (i.e., phosphoric acid). Compared to filaments loaded with phosphoric acid that require an additional benzene carburization step, the Nd ionization efficiencies (atoms detected relative to atoms loaded) for heated filaments loaded with MOF-253 were similar (∼1%). Electron microscopy after TIMS analysis demonstrated that the MOF was retained on the filament. While these results are preliminary, they demonstrate that MOFs have potential to enhance ionization and exceed the performance of traditional loading techniques by forming nanoporous ion emitters. Thus, further experimentation is likely to exceed this performance through more specific selection of the base MOF structure and modifications to porosity and composition. This work represents a novel application of MOFs and a next step in the pursuit of advanced thermal ionization with potential to expand across the periodic table.

Point-of-Care Ultrasound Diagnosis of High Flow Priapism.

BACKGROUND: Priapism can be categorized as low flow or high flow. Low flow priapism is a compartment syndrome and requires immediate treatment to avoid long-term ischemic damage. Alternatively, high flow priapism is not an emergent condition and can be managed as an outpatient. The diagnosis has traditionally been made via cavernosal blood gas analysis; however, this is painful and can cause iatrogenic harm. CASE REPORT: We present a case of high flow priapism whereby point-of-care ultrasound (POCUS) identified the presence of pulsatile cavernosal arterial flow to confirm the diagnosis. This is the first case report in the emergency medicine literature to highlight the utility of POCUS in the diagnosis and management of high flow priapism. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Low flow priapism accounts for 95% of cases and is a urologic emergency requiring immediate invasive intervention. High flow priapism is much less common and does not require emergent management. While blood gas analysis can differentiate between high and low flow priapism, POCUS is a rapid, noninvasive, accurate diagnostic means to identify the presence or absence of cavernosal pulsatile arterial flow.

Disparities in TKA Outcomes: Census Tract Data Show Interactions Between Race and Poverty.

BACKGROUND: Race is an important predictor of TKA outcomes in the United States; however, analyses of race can be confounded by socioeconomic factors, which can result in difficulty determining the root cause of disparate outcomes after TKA. QUESTIONS/PURPOSES: We asked: (1) Are race and socioeconomic factors at the individual level associated with patient-reported pain and function 2 years after TKA? (2) What is the interaction between race and community poverty and patient-reported pain and function 2 years after TKA? METHODS: We identified all patients undergoing TKA enrolled in a hospital-based registry between 2007 and 2011 who provided 2-year outcomes and lived in New York, Connecticut, or New Jersey. Of patients approached to participate in the registry, more than 82% consented and provided baseline data, and of these patients, 72% provided 2-year data. Proportions of patients with complete followup at 2 years were lower among blacks (57%) than whites (74%), among patients with Medicaid insurance (51%) compared with patients without Medicaid insurance (72%), and among patients without a college education (67%) compared with those with a college education (71%). Our final study cohort consisted of 4035 patients, 3841 (95%) of whom were white and 194 (5%) of whom were black. Using geocoding, we linked individual-level registry data to US census tracts data through patient addresses. We constructed a multivariate linear mixed-effect model in multilevel frameworks to assess the interaction between race and census tract poverty on WOMAC pain and function scores 2 years after TKA. We defined a clinically important effect as 10 points on the WOMAC (which is scaled from 1 to 100 points, with higher scores being better). RESULTS: Race, education, patient expectations, and baseline WOMAC scores are all associated with 2-year WOMAC pain and function; however, the effect sizes were small, and below the threshold of clinical importance. Whites and blacks from census tracts with less than 10% poverty have similar levels of pain and function 2 years after TKA (WOMAC pain, 1.01 ± 1.59 points lower for blacks than for whites, p = 0.53; WOMAC function, 2.32 ± 1.56 lower for blacks than for whites, p = 0.14). WOMAC pain and function scores 2 years after TKA worsen with increasing levels of community poverty, but do so to a greater extent among blacks than whites. Disparities in pain and function between blacks and whites are evident only in the poorest communities; decreasing in a linear fashion as poverty increases. In census tracts with greater than 40% poverty, blacks score 6 ± 3 points lower (worse) than whites for WOMAC pain (p = 0.03) and 7 ± 3 points lower than whites for WOMAC function (p = 0.01). CONCLUSIONS: Blacks and whites living in communities with little poverty have similar patient-reported TKA outcomes, whereas in communities with high levels of poverty, there are important racial disparities. Efforts to improve TKA outcomes among blacks will need to address individual- and community-level socioeconomic factors. LEVEL OF EVIDENCE: Level III, therapeutic study.

Anaphylaxis: Emergency Department Treatment.

Anaphylaxis is a potentially life-threatening, multisystem allergic reaction that can cause airway, breathing, or circulatory compromise. Intramuscular epinephrine is the immediate treatment of all patients. Intravenous epinephrine should be used in patients in shock, either as a bolus or infusion, along with fluid resuscitation. Airway obstruction must be recognized, and early intubation may be necessary. For shock that is refractory to epinephrine, additional vasopressors may be needed. Disposition depends on patient presentation and response to treatment. Mandatory observation periods are not necessary, because biphasic reactions are difficult to predict and may occur outside of typical observation periods.

Role of Transition Metals in Metal-Organic Frameworks as Nanoporous Ion Emitters for Thermal Ionization Mass Spectrometry.

Thermal ionization mass spectrometry is a powerful analytical technique that allows for precise determination of isotopic ratios. Analysis of low abundance samples, however, can be limited by the ionization efficiency. Following an investigation into a new type of metal-organic hybrid material, nanoporous ion emitters (nano-PIEs), devised to promote the emission of analyte ions and reduce traditional sample loading challenges, this work evaluates the impact that changing the metal in the material has on the ionization of uranium (U). Being derived from metal-organic frameworks (MOFs), nano-PIEs inherit the tunability of their parent MOFs. The MOF-74 series has been well studied for probing the impact various framework metals (i.e., Mg, Mn, Co, Ni, Cu, Zn, and Cd) have on material properties, and thus, a series of nano-PIEs with different metals were derived from this isoreticular MOF series. Trends in ionization efficiency were studied as a function of ionization potential, volatility, and work function of the framework metals to gain a better understanding of the mechanism of analyte ionization. This study finds a correlation between the analyte ionization efficiency and nano-PIE framework metal volatility that is attributed to its tunable thermal stability and degradation behavior.

Anaphylaxis: Emergency Department Treatment.

Anaphylaxis is a potentially life-threatening, multisystem allergic reaction that can cause airway, breathing, or circulatory compromise. Intramuscular epinephrine is the immediate treatment of all patients. Intravenous epinephrine should be used in patients in shock, either as a bolus or infusion, along with fluid resuscitation. Airway obstruction must be recognized, and early intubation may be necessary. For shock that is refractory to epinephrine, additional vasopressors may be needed. Disposition depends on patient presentation and response to treatment. Mandatory observation periods are not necessary, because biphasic reactions are difficult to predict and may occur outside of typical observation periods.

Heart Failure With Preserved Ejection Fraction and Diabetes: JACC State-of-the-Art Review.

Heart failure with preserved ejection fraction (HFpEF) is now the most common form of HF, affecting over 3 million adults in the United States alone. HFpEF is a heterogenous syndrome. One important phenotype may be related to comorbid conditions, including diabetes mellitus (DM). DM has a prevalence of approximately 45% in HFpEF, but characteristics and outcomes of this population are poorly understood. In this review, the authors summarize data from several clinical trials of HFpEF therapeutics and provide original data from a large cohort using the Get With The Guidelines-HF registry, which together suggest that DM is associated with increased morbidity and long-term mortality in HFpEF. The authors then discuss several common pathological mechanisms in HFpEF and DM, including sodium retention, metabolic derangements, impaired skeletal muscle function, and potential therapeutic targets. As the understanding of comorbid HFpEF and DM improves, it is hoped clinicians will be better equipped to offer effective, patient-centered treatments.

Modulation of the central opioid system as an antidepressant target in rodent models.

There has been a resurgence in interest in the central opioid system as a target in the treatment of depression. Using a range of laboratory rodent tests, potential antidepressant properties have been most associated with kappa opioid receptor antagonists, delta opioid receptor agonists, and nociceptin/orphanin FQ receptor antagonists. Although most studies to date have assessed acute behavioral effects, more elaborate investigations have demonstrated activity following repeated administration. Concerns over adverse effects have meant that opioid candidates need to be examined for their abuse potential, locomotor stimulant, and other adverse effects that might reside by activating a certain receptor subtype. The interplay between the central opioid and monoaminergic systems has been established with many clinically used antidepressants exhibiting affinity for opioid receptors that could contribute to their therapeutic effect. Similarly currently marketed opioid drugs such as tramadol possess antidepressant properties. More recent investigations have begun to examine combining of opioid agents, conferring unique profiles. This approach acknowledges that targeting a single opioid receptor may not be sufficient to produce the balanced profile of therapeutic effects, while minimizing adverse effects. As these compounds begin to reach the clinical stage, hopefully they will represent an important addition to the armamentarium to treat depression.

Engaging patients throughout the health system: A landscape analysis of cold-call policies and recommendations for future policy change.

Healthcare institutions may often prohibit "cold-calling" or direct contact with a potential research participant when the person initiating contact is unknown to the patient. This policy aims to maintain patient privacy, but may have unintended consequences as a result of physician gatekeeping. In this review, we discuss recruitment policies at the top academic institutions. We propose an ethical framework for evaluating cold-call policies based on three principles of research ethics. In order to maximize engagement of potential research participants, while maintaining patient privacy and autonomy, we then propose several alternative solutions to restrictive cold-call policies, including opt-in or opt-out platforms, a team-based approach, electronic solutions, and best practices for recruitment. As healthcare has evolved with more collaborative, patient-centered, data-driven care, the engagement of potential research participants should similarly evolve.

The emerging role of novel antihyperglycemic agents in the treatment of heart failure and diabetes: A focus on cardiorenal outcomes.

Heart failure (HF) and type 2 diabetes mellitus (T2DM) are two global pandemics, affecting over 25 and 420 million people, respectively. The prevalence of comorbid HF and T2DM is rising, and the prognosis remains poor. One central area of overlap of these two disease processes is renal dysfunction, which contributes to poor cardiovascular outcomes and mortality. As such, there is a growing need for antihyperglycemic agents with cardio- and renoprotective effects. Three classes of novel antihyperglycemic agents, sodium-glucose cotransporter-2 (SGLT2) inhibitors, glucagon-like peptide-1 receptor agonists (GLP-1RA), and dipeptidyl peptidase-4 (DPP4) inhibitors have demonstrated varied cardiorenal outcomes in recent cardiovascular outcomes trials. Understanding the differential effects of these agents, together with their proposed mechanisms, is crucial for the development of safe and effective treatment regimens and future pharmacologic targets for HF and T2DM. In this review, we discuss the overlapping pathophysiology of HF and T2DM, summarize outcomes data for the novel antihyperglycemic agents and proposed mechanisms of action, and review how the current evidence informs future management of comorbid HF and T2DM.

Uranium mobility across annual growth rings in three deciduous tree species.

Black walnut (Juglans nigra), slippery elm (Ulmus rubra), and white ash (Fraxinus americana) trees were evaluated as potential archives of past uranium (U) contamination. Like other metals, U mobility in annual growth rings of trees is dependent on the tree species. Uranium concentrations and isotopic compositions (masses 234, 235, 236, and 238) were analyzed by thermal ionization mass spectrometry to test the efficacy of using tree rings to retroactively monitor U pollution from the FFMPC, a U purification facility operating from 1951 to 1989. This study found non-natural U (depleted U and detectable 236U) in growth rings of all three tree species that pre-dated the start of operations at FFMPC and compositional trends that did not correspond with known contamination events. Therefore, the annual growth rings of these tree species cannot be used to reliably monitor the chronology of U contamination.

Higher Total Knee Arthroplasty Revision Rates Among United States Blacks Than Whites: A Systematic Literature Review and Meta-Analysis.

BACKGROUND: Reportedly 2% to 5.7% of total knee arthroplasties (TKAs) require revision within 5 years. The purpose of this study was to determine whether blacks are at higher risk of TKA revision than whites in the United States. METHODS: We performed a systematic review of English-language articles published from 2000 to 2015. Study inclusion criteria were (1) performance of the study in the United States, (2) TKA as the primary procedure studied, (3) a follow-up period at least 2 years, (4) reporting of revision rates, and (5) analysis of patient race as an independent predictor of revision. We then performed a random-effects meta-analysis to calculate a pooled hazard ratio for TKA revision in blacks compared with whites. RESULTS: A total of 4,286 studies were identified and screened by title; 106, by abstract; and 24, by full text. Six studies met the inclusion criteria. Only 4 of the 6 studies could undergo meta-analysis because of overlapping study populations in 3 of them. The meta-analysis represented 451,960 patients who underwent TKA, of whom 28,772 (6.4%) were black. Of the total, 31,568 patients (7.0%) underwent revision surgery. The risk of revision TKA was significantly higher among blacks than whites (pooled hazard ratio, 1.38; 95% confidence interval, 1.20 to 1.58; p < 0.001). Analysis of the 3 studies with overlapping study populations demonstrated discordant results as a result of adjustment compared with non-adjustment for insurance eligibility, a surrogate for socioeconomic status. CONCLUSIONS: Blacks in the United States are at higher risk of revision TKA than whites. Socioeconomic status contributed to revision risk and is an important confounder in analyses of race. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Disparities in Outcomes for African Americans and Whites Undergoing Total Knee Arthroplasty: A Systematic Literature Review.

OBJECTIVE: African Americans in the United States undergo total knee arthroplasty (TKA) less often than whites, in part because of lower expectations among African Americans for successful surgery. Whether this lower expectation is justified is unknown. Our objective is to compare health-related quality of life (HRQOL) and satisfaction after TKA between African Americans and whites. METHODS: A systematic review of English language articles using Medline, the Cochrane register, Embase (April 21, 2015), and a hand search of unlisted disparities journals was performed. Search terms included total knee replacement, quality of life, outcomes, and satisfaction. High-quality cohort studies that examined HRQOL in African Americans and white adults 6 months or more after TKA were included. RESULTS: Of the 4781 studies screened by title, and 346 by abstract, 7 studies included race in their analysis. Results included 5570 TKA patients, 4077 whites (89%), and 482 (11%) blacks. Because studies used different outcome measures and were inconsistent in their adjustment for confounders, we could not perform a quantitative synthesis of results. In 5 studies, US blacks had worse pain, in 5 worse function, and in 1 less satisfaction 6 months to 2 years after TKA. CONCLUSION: US blacks may derive less benefit from TKA than whites as measured by HRQOL, pain, function, and satisfaction. Many studies assessing predictors of patient-related TKA outcomes fail to analyze race as a variable, which limited our study. More studies assessing the effect of race and socioeconomic factors on TKA outcome are needed.