Donor utilization in heart transplant with donation after circulatory death in the United States.

Heart transplantation using donation after circulatory death (DCD) was recently adopted in the United States. This study aimed to characterize organ yield from adult (≥18 years) DCD heart donors in the United States using the United Network for Organ Sharing registry. The registry does not identify potential donors who do not progress to circulatory death, and only those who progressed to death were included for analysis. Outcomes included organ recovery from the donor operating room and organ utilization for transplant. Multiple logistic regression was used to identify predictors of heart recovery and utilization. Among 558 DCD procurements, recovery occurred in 89.6%, and 92.5% of recovered hearts were utilized for transplant. Of 506 DCD procurements with available data, 65.0% were classified as direct procurement and perfusion and 35.0% were classified as normothermic regional perfusion (NRP). Logistic regression identified that NRP, shorter agonal time, younger donor age, and highest volume of organ procurement organizations were independently associated with increased odds for heart recovery. NRP independently predicted heart utilization after recovery. DCD heart utilization in the United States is satisfactory and consistent with international experience. NRP procurements have a higher yield for DCD heart transplantation compared with direct procurement and perfusion, which may reflect differences in donor assessment and acceptance criteria.

PBMC-derived extracellular vesicles in a smoking-related inflammatory disease model.

Extracellular vesicles (EVs) function as mediators of intercellular communication and as such influence the recipient cell function. EVs derived from immune cells can carry out many of the same functions as their parental cells, as they carry costimulatory molecules, antigens, and antigen-MHC complexes. As a result, there is a strong interest in understanding the composition and origin of immune cell-derived EVs in order to understand their role in the pathogenesis of diseases. This study aimed to optimize methodologies to study immune cell-derived EVs. Peripheral blood mononuclear cell-derived small EVs were isolated and observed using conventional transmission electron microscopy and sized by nanoparticle tracking analysis. They were then enumerated and profiled using imaging flow cytometry and were further characterized using a flow cytometric multiplex bead assay. These techniques were then applied to our current research, namely smoking-related inflammatory disease. We present here a comprehensive approach to analyze PBMC-derived small EVs in smoking-related inflammatory disease following the Minimal Information for Studies of Extracellular Vesicle 2018 guidelines.

Tobacco industry interference to undermine the development and implementation of graphic health warnings in Bangladesh.

BACKGROUND: In Bangladesh, the 2013 Amendment of the Tobacco Control Act made graphic health warnings (GHWs) on the upper 50% of all tobacco packs obligatory. However, at the time of writing (May 2022), GHWs are still being printed on the lower 50% of packs. This paper seeks to explore how the tobacco industry undermined the development and implementation of GHWs in Bangladesh, a country known for a high level of tobacco industry interference (TII) that has rarely been examined in the peer-reviewed literature. METHODS: Analysis of print and electronic media articles and documents. RESULTS: Cigarette companies actively opposed GHWs, while bidi companies did not. The primary strategy used to influence the formulation and delay the implementation of GHWs was direct lobbying by the Bangladesh Cigarette Manufacturers' Association and British American Tobacco Bangladesh. Their arguments stressed the economic benefits of tobacco to Bangladesh and sought to create confusion about the impact of GHWs, for example, claiming that GHWs would obscure tax banderols, thus threatening revenue collection. They also claimed technical barriers to implementation-that new machinery would be needed-leading to delays. Tensions between government bodies were identified, one of which (National Board of Revenue)-seemingly close to cigarette companies and representing their arguments-sought to influence others to adopt industry-preferred positions. Finally, although tobacco control advocates were partially successful in counteracting TII, one self-proclaimed tobacco control group, whose nature remains unclear, threatened the otherwise united approach. CONCLUSIONS: The strategies cigarette companies used closely resemble key techniques from the well-evidenced tobacco industry playbook. The study underlines the importance of continuing monitoring and investigations into industry conduct and suspicious actors. Prioritising the implementation of WHO Framework Convention on Tobacco Control Article 5.3 is crucial for advancing tobacco control, particularly in places like Bangladesh, where close government-industry links exist.

The impact of changes in renal function during waitlist time on outcomes after heart transplantation.

BACKGROUND AND AIM: This study evaluated the impact of changes in renal function during the waitlist period on posttransplant outcomes of orthotopic heart transplantation (OHT). METHODS: The United Network for Organ Sharing registry was used to identify adult patients undergoing isolated OHT from 2010 to 2020. Patients were stratified by whether their National Kidney Foundation chronic kidney disease (CKD) stage improved, worsened, or remained unchanged between listing and transplantation. Univariate analysis and multivariable Cox regression were conducted to determine whether a change in estimated glomerular filtration rate (eGFR) or change in CKD stage predicted 1-year mortality after OHT. RESULTS: Of 22,746 patients, the majority of patients remained in the same CKD stage (59.6%), and the frequencies of patients progressing to improved (19.3%) and worsened (21.1%) CKD stages were similar. Temporary mechanical circulatory support (MCS) was associated with improved CKD stage and durable MCS with worsened CKD stage (p < .001). Post-OHT dialysis was most common in patients with worsened CKD stage (13.2%) and least common in the improved cohort (9.4%) (p < .001). Kaplan-Meier unadjusted 1-year survival rates after OHT were similar between CKD change groups (log-rank p = .197). Multivariable analysis demonstrated no risk-adjusted effect of change in eGFR (p = .113) or change in CKD stage (p = .076) on 1-year mortality after OHT. CONCLUSIONS: Approximately 20% of patients improve CKD stage and 20% worsen CKD stage between listing and OHT, with the remaining 60% having unchanged CKD stage. Worsening CKD stage predicts increased likelihood of post-OHT dialysis, but CKD stage change does not predict 1-year survival following OHT.

Risk of recipient age on 1-year mortality after simultaneous heart-lung transplantation.

BACKGROUND: Heart-lung transplantation (HLTx) is relatively uncommon, and there is a paucity of literature to suggest an age at which older recipients may be exposed to excess risk for mortality. This analysis aimed to identify a threshold of age that predicts adverse outcomes after HLTx. METHODS: The United Network of Organ Sharing registry was used to identify adult patients undergoing HLTx from 2005 to 2021. The primary outcome was 1-year mortality. Threshold regression was used to identify the threshold at which age impacts 1-year mortality. Kaplan-Meier analysis was used to model survival, and Cox proportional hazards modeling was used for risk-adjustment. RESULTS: We identified 453 patients undergoing HLTx. Threshold analysis identified that the risk for 1-year mortality was significantly elevated beyond an age of 58 years, and 47 (10.38%) patients were older than this threshold. On Kaplan-Meier analysis, 1-year survival was significantly lower in patients > 58 years compared to younger recipients (64.7% vs. 82.0%, p = .007). After risk adjustment, the hazard ratio for 1-year mortality in recipients older than 58 years was 2.27 (95% confidence interval [1.21-4.28], p = .011). CONCLUSION: A threshold for recipient age of 58 years of age may avoid excess 1-year mortality after HLTx. However, patients older than this threshold demonstrate acceptable early and midterm survival, and the majority survive to 1 year. Advanced age should be considered in patient selection for HLTx, but may not be a contraindication for candidacy particularly in the absence of other risk factors.

One-year outcomes of supersaturated oxygen therapy in acute anterior myocardial infarction: The IC-HOT study.

BACKGROUND: Supersaturated oxygen (SSO2 ) has recently been approved by the U.S. Food and Drug Administration for administration after primary percutaneous coronary intervention (pPCI) in patients with anterior ST-segment elevation myocardial infarction (STEMI) based on its demonstration of infarct size reduction in the IC-HOT study. OBJECTIVES: To describe the 1-year clinical outcomes of intracoronary SSO2 treatment after pPCI in patients with anterior STEMI. METHODS: IC-HOT was a prospective, open-label, single-arm study in which 100 patients without cardiogenic shock undergoing successful pPCI of an occluded left anterior descending coronary artery were treated with a 60-min SSO2 infusion. One-year clinical outcomes were compared with a propensity-matched control group of similar patients with anterior STEMI enrolled in the INFUSE-AMI trial. RESULTS: Baseline and postprocedural characteristics were similar in the two groups except for pre-PCI thrombolysis in myocardial infarction 3 flow, which was less prevalent in patients treated with SSO2 (9.6% vs. 22.9%, p = .02). Treatment with SSO2 was associated with a lower 1-year rate of the composite endpoint of all-cause death or new-onset heart failure (HF) or hospitalization for HF (0.0% vs. 12.3%, p = .001). All-cause mortality, driven by cardiovascular mortality, and new-onset HF or HF hospitalization were each individually lower in SSO2 -treated patients. There were no significant differences between groups in the 1-year rates of reinfarction or clinically driven target vessel revascularization. CONCLUSIONS: Infusion of SSO2 following pPCI in patients with anterior STEMI was associated with improved 1-year clinical outcomes including lower rates of death and new-onset HF or HF hospitalizations.

Short-Term Exposure to Waterpipe/Hookah Smoke Triggers a Hyperactive Platelet Activation State and Increases the Risk of Thrombogenesis.

OBJECTIVE: Cardiovascular disease is a major public health problem. Among cardiovascular disease's risk factors, tobacco smoking is considered the single most preventable cause of death, with thrombosis being the main mechanism of cardiovascular disease mortality in smokers. While tobacco smoking has been on the decline, the use of waterpipes/hookah has been rising, mainly due to the perception that they are less harmful than regular cigarettes. Strikingly, there are few studies on the negative effects of waterpipes on the cardiovascular system, and none regarding their direct contribution to thrombus formation. Approach and Results: We used a waterpipe whole-body exposure protocol that mimics real-life human exposure scenarios and investigated its effects, relative to clean air, on platelet function, hemostasis, and thrombogenesis. We found that waterpipe smoke (WPS)-exposed mice exhibited both shortened thrombus occlusion and bleeding times. Further, our results show that platelets from WPS-exposed mice are hyperactive, with enhanced agonist-induced aggregation, dense and α-granule secretion, αIIbß3 integrin activation, phosphatidylserine expression, and platelet spreading, when compared with clean air-exposed platelets. Finally, at the molecular level, it was found that Akt (protein kinase B) and ERK (extracellular signal-regulated kinases) phosphorylation are enhanced in the WPS and in nicotine-treated platelets. CONCLUSIONS: Our findings demonstrate that WPS exposure directly modulates hemostasis and increases the risk of thrombosis and that this is mediated, in part, via a state of platelet hyperactivity. The negative health impact of WPS/hookah, therefore, should not be underestimated. Moreover, this study should also help in raising public awareness of the toxic effects of waterpipe/hookah.

Grand rounds education in neurology, with a focus on headache medicine.

OBJECTIVE: To quantify the proportion of headache-related grand rounds in academic neurology programs and to compare this with adult neurology residency director views on the need for an increase in headache-related grand rounds. BACKGROUND: Although headache are among the most prevalent and most burdensome neurologic conditions, headache medicine is often considered underrepresented in neurology departments. Additionally, prior studies have shown that many neurology residency directors feel that training programs do not include an adequate amount of exposure to headache clinics or headache-related didactics. One important aspect of didactic education in neurology departments is adult neurology grand rounds. Previous publications have evaluated neither the proportion of headache-related grand rounds in academic neurology departments nor the residency program directors' views on appropriate amount of headache-related grand rounds. Our study has attempted to quantify this information to elucidate opportunities to improve practice educational gaps. METHODS: In this cross-sectional study, we surveyed adult neurology residency directors (from the Accreditation Council for Graduate Medical Education [ACGME] listing of academic adult neurology residency programs) between October 2018 and September 2019. In addition, we used two methods to obtain the proportion of headache-related grand rounds in neurology: (1) emailing residency directors a questionnaire asking for a list of prior grand rounds topics and (2) an online search for each academic neurology program. RESULTS: First, for our grand rounds analysis, headache medicine consisted of 3.7% of the lectures in 2017-2018 and 6.3% of the lectures in 2018-2019 (average of each institution; 17 institutions and 411 total lectures in 2017-2018, 21 institutions and 463 total lectures in 2018-2019). The most common number of lectures on headache medicine for each grand rounds series was zero (for 7 of 17 grand rounds series in 2017-2018 and 7 of 21 in 2018-2019), followed closely by one lecture (for 6 of 17 grand rounds series in 2017-2018 and 6 of 21 in 2018-2019). Second, for our survey, the response rate was 19.3% (29/150). No residency director thought their institution had too many grand rounds dedicated to headache medicine, and 62.1% (18/29) thought they had an adequate amount of headache grand rounds. Within the survey responders, 75.9% (22/29) of adult neurology residency programs have a board-certified headache specialist at their institution. CONCLUSIONS: Although most adult neurology residency directors believe that headache is adequately represented in adult neurology grand rounds, headache medicine makes up 4%-6% of all neurology grand rounds. Compared with other neurology subspecialties and the other core ACGME milestones, headache makes up the fewest grand rounds lectures that were assessed in this study.

Evaluation of intracoronary hyperoxemic oxygen therapy in acute anterior myocardial infarction: The IC-HOT study.

BACKGROUND: In the randomized AMIHOT-II trial, supersaturated oxygen [SSO2 ] delivered into the left anterior descending (LAD) artery via an indwelling intracoronary infusion catheter following primary percutaneous coronary intervention (PCI) significantly reduced infarct size in patients with anterior ST-segment elevation myocardial infarction (STEMI) but resulted in a numerically higher incidence of safety events. OBJECTIVES: The IC-HOT study evaluated the safety of SSO2 therapy selectively delivered to the left main coronary artery (LMCA) for 60 minutes after PCI in patients with anterior STEMI. METHODS: SSO2 therapy was administered to the LMCA after stent implantation in 100 patients with anterior STEMI and proximal or mid-LAD occlusion presenting within 6 hours of symptom onset. The primary endpoint was the 30-day composite rate of net adverse clinical events (NACE) (death, reinfarction, clinically driven target vessel revascularization, stent thrombosis, severe heart failure, or TIMI major/minor bleeding) compared against an objective performance goal of 10.7%. Cardiac magnetic resonance imaging was performed at 4 and 30 days to assess infarct size. RESULTS: SSO2 delivery was successful in 98% of patients. NACE at 30 days occurred 7.1% of patients (meeting the primary safety endpoint of the study); there were no deaths, only one stent thrombosis and one case of severe heart failure. Median [interquartile range] infarct size was 24.1% [14.4%, 31.6%] at 4 days and 19.4% [8.8%, 28.9%] at 30 days. CONCLUSION: Following primary PCI in acute anterior STEMI, infusion of SSO2 via the LMCA was feasible and was associated with a favorable early safety profile.

Ocular and cerebral infarction from periocular filler injection.

A 20-year-old woman presented with loss of vision in her right eye and a "black nose" after receiving hyaluronic acid filler injections in her right glabella 1 month prior. Her vision was no light perception, and external examination revealed resolving skin necrosis at the nasal tip. A dilated fundus exam showed a fibrotic membrane emanating from a pale optic nerve and a diffusely atrophic retina with sclerotic vessels. An MRI demonstrated scattered right-sided parietal lobe infarcts. These findings were consistent with inadvertent cannulation of the supraorbital artery, followed by injection of filler into the internal carotid circulation. The product traveled in a retrograde fashion, occluding the right ophthalmic artery, right dorsal nasal artery, and arterial segments to the Circle of Willis. This case highlights the importance of understanding the complex vascular architecture of the periorbita and the mechanism by which such occlusions occur.

The effects of hookah/waterpipe smoking on general health and the cardiovascular system.

Hookah or waterpipe smoking or use is an emerging trend in the US population, especially among the youth. The misperception of hookah being less harmful than cigarettes and the availability of different but "appealing" flavors are considered among the main reasons for this trend. Hookah users however are exposed to many of the same toxic compounds/by-products as cigarette users, but at dramatically higher levels, which might lead to more severe negative health effects. In fact, hookah users are at risks of infections, cancers, lung disease, and other medical conditions. Moreover, because of the overlapping toxicant/chemical profile to conventional cigarettes, hookah smoke effects on the cardiovascular system are thought to be comparable to those of conventional cigarettes. A major source of tobacco addiction is nicotine, whose levels in hookah are extremely variable as they depend on the type of tobacco used. Taken together, in this review of literature, we will provide insights on the negative health effects of hookah in general, with a focus on what is known regarding its impact on the cardiovascular system.

Role of IκB kinase ß in regulating the remodeling of the CARMA1-Bcl10-MALT1 complex.

The current work investigates the notion that inducible clustering of signaling mediators of the IKK pathway is important for platelet activation. Thus, while the CARMA1, Bcl10, and MALT1 (CBM) complex is essential for triggering IKK/NF-κB activation upon platelet stimulation, the signals that elicit its formation and downstream effector activation remain elusive. We demonstrate herein that IKKß is involved in membrane fusion, and serves as a critical protein kinase required for initial formation and the regulation of the CARMA1/MALT1/Bcl10/CBM complex in platelets. We also show that IKKß regulates these processes via modulation of phosphorylation of Bcl10 and IKKγ polyubiquitination. Collectively, our data demonstrate that IKKß regulates membrane fusion and the remodeling of the CBM complex formation.

Occult invasion of sternothyroid muscle by differentiated thyroid cancer.

PURPOSE: To determine the incidence of occult invasion of sternothyroid by differentiated thyroid cancer (DTC) and identify clinico-pathological features associated with the same. METHODS: Retrospective study of a consecutive series of DTC patients undergoing surgery, with preoperative ultrasound showing no evidence of strap muscle invasion. All had en bloc excision of sternothyroid muscle along with thyroidectomy. Incidence of microscopic invasion of sternothyroid and clinicopathologic features associated with the same, were studied. RESULTS: A total of 76 patients with DTC (2010-2014) were identified, of whom 62 met the inclusion criteria and were included in this study. Of these, 22 (36%) had no extrathyroidal extension (ETE), 30 (48%) had minimal ETE without sternothyroid invasion and 10 (16%) had minimal ETE with microscopic sternothyroid invasion. The mean tumor sizes of the three sub-groups were 1.9, 3.1 and 4.9 cm, respectively, with a significant difference between no ETE and sternothyroid invaded sub-groups (p = 0.03). Out of the 40 cases with minimal ETE, 3 (7.5%) had positive tumor microscopic margin. Retaining sternothyroid in situ would have theoretically increased this proportion to 27.5%. Over a median follow-up of 52 months, 58 (94%) patients remained structurally disease free, with only 1 local recurrence. CONCLUSION: Occult invasion of sternothyroid muscle occurred in 16% of DTC in this series. Excision of the muscle en bloc with thyroidectomy, particularly in larger tumors, may confer benefit in accurately staging the disease, encompassing occult ETE and achieving clear microscopic margins.

CXCL12 regulates platelet activation via the regulator of G-protein signaling 16.

The regulators of G protein signaling (RGS) protein superfamily negatively controls G protein-coupled receptor signal transduction pathways. One of the members of this family, RGS16, is highly expressed in megakaryocytes and platelets. Studies of its function in platelet and megakaryocyte biology have been limited, in part, due to lack of pharmacological inhibitors. For example, RGS16 overexpression inhibited CXC chemokine receptor 4 (CXCR4)-mediated megakaryocyte migration. More recent studies showed that the chemokine stromal cell-derived factor (SDF1α or CXCL12) regulates platelet function via CXCR4. Based on these considerations, the present study investigated the capacity of RGS16 to regulate CXCL12-dependent platelet function, using the RGS16 knockout mouse model (Rgs16(-/-)). RGS16-deficient platelets had increased protease activated receptor 4 and collagen-induced aggregation, as well as increased CXCL12-dependent agonist-induced aggregation, dense and alpha granule secretion, integrin αIIbß3 activation and phosphatidylserine exposure compared to those from WT littermates. CXCL12 alone did not stimulate aggregation or secretion in either RGS16-deficient or WT platelets. Furthermore, platelets from Rgs16(-/-) mice displayed enhanced phosphorylation of ERK and Akt following CXCL12 stimulation relative to controls. Finally, we also found that PKCδ is involved in regulating CXCL12-dependent activation of ERK and Akt, in the Rgs16-deficient platelets. Collectively, our findings provide the first evidence that RGS16 plays an important role in platelet function by modulating CXCL12-dependent platelet activation.

P2Y12 antibody inhibits platelet activity and protects against thrombogenesis.

Given that platelet hyperactivity is known to give rise to thrombotic disorders, new and/or novel antiplatelet therapies are constantly being developed to add to, or to complement the current arsenal of agents. To this end, adenosine diphosphate (ADP) is an important platelet activator that acts by binding to the G-protein coupled P2Y1 and P2Y12 receptors. Although the contribution of the P2Y12 receptor to the genesis of thrombosis is well established, the parenteral arsenal of drugs targeting this receptor in clinical use is limited to cangrelor. In this study, we investigated the potential antiplatelet activity of an antibody targeting the ligand-binding domain of the P2Y12 receptor (abbreviated P2Y12Ab). Our in vitro studies revealed that the P2Y12Ab could effectively inhibit aggregation induced by ADP, as well as that triggered by the thromboxane receptor agonist U46619. Additionally, using FACS analysis, we observed reduced P-selectin, phosphatidylserine exposure and integrin activation in the presence of P2Y12Ab. As for its in vivo effects, the P2Y12Ab also demonstrated protection against thrombus formation; albeit this was accompanied with a bleeding diathesis (longer bleeding time). Notably, this inhibitory profile is consistent with that observed with oral anti-P2Y12 agents. Collectively, our findings demonstrate that the P2Y12Ab functionally blocks platelet activity in vitro and in vivo, and support the notion that it can be purposed as a parenteral antiplatelet agent, to be used in conjunction with and/or as a complement to current antiplatelet therapies.

An Algorithm for Opioid and Barbiturate Reduction in the Acute Management of Headache in the Emergency Department.

OBJECTIVE: To develop and implement an algorithm for the management of headaches presenting to the emergency department (ED) in order to decrease the frequency of opioid and barbiturate treatment both acutely as well as on discharge. BACKGROUND: Headache is the fifth leading cause of ED visits in the United States. In the case of primary headache, particularly migraine, treatment in the ED can be highly variable. Patients with migraine continue to be treated with opioids more commonly than nonopioid, migraine specific medications. In addition, discharge plans seldom include measures to prevent recurrence or instructions to re-treat if pain persists. At this time, there is no standardized management protocol directed at acute headaches presenting to the ED. METHODS: An ED headache treatment algorithm with step-wise instructions for diagnosis, treatment, and discharge planning was piloted at Lakewood Hospital, a regional Cleveland Clinic affiliated hospital. This non-randomized interventional study compared outcomes after implementation of the algorithm to historical controls. Patient demographic data including age, gender, and payer mix was collected. Outcomes measured included the frequency of treatment with opioids or barbiturates, imaging, neurology consults, admissions, and a patient reported pain score. Data relevant to patient disposition and follow-up, including prescriptions for opioids or barbiturates given at discharge, and ensuring PCP or neurology follow-up appointments at discharge was also reviewed. RESULTS: Demographic data did not differ significantly between the pre- and post-algorithm groups. There was a significant decline in the number of patients treated with opioids and barbiturates from 66.0% pre-algorithm to 6.8% immediately after algorithm implementation (P <. 001), and to 28% (P < .001) one year after algorithm implementation, indicating both an immediate effect of the algorithm and a sustained effect. Similarly, pre-algorithm implementation, 37% of patients were discharged with a prescription for opioids or barbiturates as compared to 12% and 6% in the early post-algorithm cohort and at 1 year, respectively. There was also an increase in scheduled follow-up appointments after discharge from the ED from 59% to 98% immediately post algorithm (P < .001). Other measures including the frequency of imaging, and patient reported pain did not significantly change. There was a significant increase in neurology consults and admissions a year after the algorithm was implemented. CONCLUSIONS: A quality improvement pilot study aimed at treating headache in an Emergency Department setting was successfully implemented in a regional Cleveland Clinic Hospital. Our results demonstrated significant decrease in acute treatment with opioids or barbiturates and a decrease in prescriptions written for opioids or barbiturates on discharge. This study is limited by small sample size. More data are needed to determine the reason for 1) increased consultation and subsequent admission after algorithm implementation and 2) decreased scheduled follow-up appointments at one-year post algorithm.

Pulse Oximeter Derived Blood Pressure Measurement in Patients With a Continuous Flow Left Ventricular Assist Device.

Currently, blood pressure (BP) measurement is obtained noninvasively in patients with continuous flow left ventricular assist device (LVAD) by placing a Doppler probe over the brachial or radial artery with inflation and deflation of a manual BP cuff. We hypothesized that replacing the Doppler probe with a finger-based pulse oximeter can yield BP measurements similar to the Doppler derived mean arterial pressure (MAP). We conducted a prospective study consisting of patients with contemporary continuous flow LVADs. In a small pilot phase I inpatient study, we compared direct arterial line measurements with an automated blood pressure (ABP) cuff, Doppler and pulse oximeter derived MAP. Our main phase II study included LVAD outpatients with a comparison between Doppler, ABP, and pulse oximeter derived MAP. A total of five phase I and 36 phase II patients were recruited during February-June 2014. In phase I, the average MAP measured by pulse oximeter was closer to arterial line MAP rather than Doppler (P = 0.06) or ABP (P < 0.01). In phase II, pulse oximeter MAP (96.6 mm Hg) was significantly closer to Doppler MAP (96.5 mm Hg) when compared to ABP (82.1 mm Hg) (P = 0.0001). Pulse oximeter derived blood pressure measurement may be as reliable as Doppler in patients with continuous flow LVADs.

Characterization of a novel function-blocking antibody targeted against the platelet P2Y1 receptor.

OBJECTIVE: Platelet hyperactivity is associated with vascular disease and contributes to the genesis of thrombotic disorders. ADP plays an important role in platelet activation and activates platelets through 2 G-protein-coupled receptors, the Gq-coupled P2Y1 receptor (P2Y1R), and the Gi-coupled P2Y12 receptor. Although the involvement of the P2Y1R in thrombogenesis is well established, there are no antagonists that are currently available for clinical use. APPROACH AND RESULTS: Our goal is to determine whether a novel antibody targeting the ligand-binding domain, ie, second extracellular loop (EL2) of the P2Y1R (EL2Ab) could inhibit platelet function and protect against thrombogenesis. Our results revealed that the EL2Ab does indeed inhibit ADP-induced platelet aggregation, in a dose-dependent manner. Furthermore, EL2Ab was found to inhibit integrin GPIIb-IIIa activation, dense and α granule secretion, and phosphatidylserine exposure. These inhibitory effects translated into protection against thrombus formation, as evident by a prolonged time for occlusion in a FeCl3-induced thrombosis model, but this was accompanied by a prolonged tail bleeding time. We also observed a dose-dependent displacement of the radiolabeled P2Y1R antagonist [(3)H]MRS2500 from its ligand-binding site by EL2Ab. CONCLUSIONS: Collectively, our findings demonstrate that EL2Ab binds to and exhibits P2Y1R-dependent function-blocking activity in the context of platelets. These results add further evidence for a role of the P2Y1R in thrombosis and validate the concept that targeting it is a relevant alternative or complement to current antiplatelet strategies.

Headache Education in Adult Neurology Residency: A Survey of Program Directors and Chief Residents.

OBJECTIVE: This cross-sectional study reassesses the status of headache didactics and clinical training in adult neurology residency programs in the United States to determine if program directors and chief residents feel that current training in headache is adequate. BACKGROUND: Headache is among the most common new complaints to both the neurology and primary care clinic and represents a significant economic burden. However, headache remains both under-diagnosed and under-treated. Of those who seek treatment only 28% report they are very satisfied with their management. One possible cause for dissatisfaction is inadequate education of treating physicians. Two studies in 2002 and 2005 that collectively surveyed all 125 adult neurology residency programs concluded that more evidence was needed to evaluate the adequacy of headache education in these programs. A survey of neurology residency department chairs and program directors in 2005 also evaluated the status of headache education in adult neurology training programs and concluded the same. METHODS: We surveyed 133 neurology residency program directors and 213 chief residents. Program directors and chief residents were asked about the amount of headache didactics, amount of clinical exposure to headache, perceived adequacy of current training and if plans existed to increase headache education through didactics or clinical exposure. RESULTS: Seventy-two program directors (54%) and 117 chief residents (55%) responded. Twenty-six percent of programs reported a mandatory headache clinic. Of these, 35% of programs reported <2 weeks of clinic, 54% of programs reported 2-4 weeks, and 12% of programs reported > 4 weeks of clinic. Fifty-one percent of program directors felt more than 4 weeks of clinical exposure to headache was needed to adequately prepare neurology residents. Ninety-six percent of program directors surveyed believed their residents were adequately prepared to diagnose and treat headache disorders. Twenty-one percent had plans to increase didactic time and 26% planned to incorporate more clinical exposure. CONCLUSIONS: Despite a modest increase in headache didactics in neurology residency programs over the last decade, many program directors and chief residents report that their programs do not include what they believe to be adequate educational experiences in headache. Although the overwhelming majority of neurology residency programs reported that residents were adequately prepared to diagnose and treat headache disorders, about a fourth of programs still felt the need to increase the amount of didactic and clinical exposure dedicated toward the management of headache disorders.