Sexual dimorphism in dinosaurs.

Studying fossils from a mass-mortality event reveals evidence for sexual dimorphism and, unusually, equal numbers of males and females in a herd of dinosaurs.

Growth Hormone Secretagogues as Potential Therapeutic Agents to Restore Growth Hormone Secretion in Older Subjects to Those Observed in Young Adults.

The discovery of the growth hormone secretagogues (GHS) and the reverse pharmacology leading to the discovery of GHS receptor which enabled the identification of ghrelin as the natural ligand for the receptor have opened a new horizon in growth hormone (GH) physiology, pathophysiology, and therapeutics. Major progress has been made and we now have orally active GHS which are able to restore optimal pulsatile GH secretion which cannot be overstimulated as insulin-like growth factor feedback regulates the peaks to the optimum level. This enables GH to be restored in the older to levels normally seen in 20- to 30-year-old people; this leads to an increase in fat-free mass and redistribution of fat to the limbs. As these agents are ultimately approved and investigated further, it is likely that they will be shown to restore growth in children with moderate-to-mild GH deficiency; their benefits will be investigated in other indications such as nonalcoholic fatty liver disease, frailty, anemia, osteoporosis, and immune compromise in older subjects. The exquisite regulation of GH secretion reflects the importance of GH pulsatility in the regulation of somatotroph action of GH.

Evaluating Adequacy of VTE Prophylaxis Dosing with Enoxaparin for Overweight and Obese Patients on an Orthopedic-Medical Trauma Comanagement Service.

OBJECTIVES: Venous thromboembolism (VTE) is a common nosocomial condition, developing frequently in overweight and obese patients. VTE prophylaxis with weight-based enoxaparin dosing may be more effective than the standard dosing regimen for overweight and obese patients; however, weight-based dosing is not practiced routinely. In this pilot study we sought to evaluate prophylactic anticoagulation regimens used for VTE prevention in overweight and obese patients on the Orthopedic-Medical Trauma (OMT) service to inform the need for modification of dosing practices. METHODS: This prospective, observational study evaluated the adequacy of current VTE prophylaxis practice at an academic tertiary center, including overweight and obese patients admitted during 2017-2018 to an OMT comanagement service. It included patients hospitalized for at least 3 days with a body mass index (BMI) of ≥25 and prescribed enoxaparin. Steady-state antifactor Xa trough and peak levels were monitored after three doses. Frequency of in prophylactic range (0.2-0.44) antifactor Xa levels and VTE events were compared by BMI groups and enoxaparin dosing using the χ2 test. RESULTS: There were 404 inpatients included: 41.1% were overweight (BMI 25-29), 43.4% were obese (BMI 30-39), and 15.6% were morbidly obese (BMI ≥40). A total of 351 patients (86.9%) received standard dose enoxaparin 30 mg 2 times per day (BID), and 53 patients received enoxaparin 40 mg BID or more. A number of patients (213; 52.7%) did not achieve prophylactic range antifactor Xa levels. A significantly higher number of patients in the overweight group achieved prophylactic range antifactor Xa compared with obese and morbidly obese groups (58.4% vs 41.7% and 33%, P = 0.002 and 0.0007, respectively). Morbidly obese patients treated with enoxaparin 40 mg BID or higher versus enoxaparin 30 mg BID had fewer VTE events (4% vs 10.8%, P = 0.18). CONCLUSIONS: The current practice of VTE enoxaparin prophylaxis may not be adequate for overweight and obese OMT patients. Further guidelines are needed to implement weight-based VTE prophylaxis in overweight and obese hospitalized patients.

Association between venous thromboembolism rates and different prophylactic anticoagulation regimens in patients undergoing free flap reconstruction of the head and neck region.

BACKGROUND: Venous Thromboembolism (VTE) is a serious complication after free tissue transfer to the head and neck (H&N). However, an optimal antithrombotic prophylaxis protocol is not defined in the literature. Enoxaparin 30 mg twice daily (BID) and heparin 5000 IU three times daily (TID) are among the most commonly used regimens for chemoprophylaxis. However, no studies compare these two agents in the H&N population. METHODS: A cohort study of patients who underwent free tissue transfer to H&N from 2012 to 2021 and received either enoxaparin 30 mg BID or Heparin 5000 IU TID postoperatively. Postoperative VTE and hematoma events were recorded within 30 days of index surgery. The cohort was divided into two groups based on chemoprophylaxis. VTE and hematoma rates were compared between the groups. RESULTS: Out of 895 patients, 737 met the inclusion criteria. The mean age and Caprini score were 60.6 [SD 12.5] years and 6.5 [SD 1.7], respectively. 234 [31.88%] were female. VTE and hematoma rates among all patients were 4.47% and 5.56%, respectively. The mean Caprini score between the enoxaparin (n = 664) and heparin (n = 73) groups was not statistically significant (6.5 ± 1.7 vs.6.3 ± 1.3, p = 0.457). The VTE rate in the enoxaparin group was significantly lower than in the heparin group (3.9% vs. 9.6%; OR: 2.602, 95% CI: 1.087-6.225). Hematoma rates were similar between the two groups (5.5% vs. 5.6%; OR: 0.982, 95% CI: 0.339-2.838). CONCLUSIONS: Enoxaparin 30 mg BID was associated with a lower VTE rate while maintaining a similar hematoma rate compared to heparin 5000 units TID. This association may support the use of enoxaparin over heparin for VTE chemoprophylaxis in H&N reconstruction.

Intravascular Lymphoma - The Creepy Crawler: A Case Series and Brief Literature Review.

BACKGROUND: Intravascular large B-cell lymphoma (IVLBCL) is a rare subtype of extranodal B-cell lymphoma, which has traditionally been associated with poor outcomes. Despite increasing recognition, IVLBCL requires a high degree of clinical suspicion on the part of the clinician for its diagnosis. CASE SERIES: We present four patient cases: A 69-year-old female with constitutional symptoms and cognitive decline; a 78-year-old female with kidney injury and constitutional symptoms whose disease rapidly progressed to multiorgan failure and death; a 70-year-old asymptomatic female with an incidentally found, enlarged thyroid; and a 63-year-old male with cytopenia and constitutional symptoms. Retrospective chart analysis was performed on these four patients diagnosed with IVLBCL at our Institute to identify the pathognomonic features of the disease and compare these to the published evidence. IVLBCL has a heterogeneous presentation, as seen in our four patients. The disease is characterized by the exclusive presence of malignant cells inside the blood vessels and lack of organ infiltration. Traditional preliminary diagnostic modalities such as imaging are usually inconclusive, given the paucity of lymphomatous aggregates. A bone marrow biopsy, random skin biopsies, or a focal organ biopsy in appropriate cases is required for diagnosis. Immunosuppression might play a role in the pathogenesis. Timely initiation of aggressive cancer-directed therapy was associated with improved outcomes. Monitoring for disease response and relapse continues to be a challenge. CONCLUSION: Our mini-series highlights the significance of timely diagnosis and intervention in IVLBCL and emphasizes the importance of further research to determine its association with immunosuppression.

Safety and efficacy of classical complement pathway inhibition with sutimlimab in chronic immune thrombocytopenia.

Chronic/refractory immune thrombocytopenia (ITP) is a rare and pathophysiologically heterogeneous disorder with variable responsiveness to available treatments. Sutimlimab, a first-in-class humanized monoclonal anti-C1s IgG4 antibody, selectively inhibits the classical pathway. This phase 1 study (NCT03275454) assessed the safety, efficacy, pharmacokinetics, and pharmacodynamics of biweekly sutimlimab in patients with chronic/refractory ITP with an inadequate response to ≥2 therapies (platelet count ≤ 30 × 109/L). Twelve patients (median age 42 years) received sutimlimab for a median of 20.5 weeks followed by a median 2-week washout period (part A). In part B, 7 of the 12 eligible patients received sutimlimab retreatment for a median of 113 weeks. In part A, the mean (standard deviation) platelet count increased from 25 × 109/L (17) to 54 × 109/L (60) 24 hours after starting sutimlimab, maintaining ≥50 × 109/L throughout part A. Five patients (42%) achieved durable platelet count responses (≥50 × 109/L in ≥50% of follow-up visits) and 4 achieved complete response (platelet count ≥100 × 109/L). The mean platelet count returned to baseline during washout and increased upon retreatment in part B. The mean platelet count improvements accompanied the rapid inhibition of the classical pathway. There were 74 treatment-emergent adverse events in part A (n = 10) and 70 in part B (n = 6). Five serious adverse events were observed; 1 event (migraine) was assessed by the investigator as related to sutimlimab. These results demonstrated that in some patients with ITP, autoantibodies activate the classical complement pathway, accelerating platelet destruction or impairing platelet production and contributing to treatment failure. Thus, C1s inhibition may be a safe and beneficial therapeutic approach for patients with chronic/refractory ITP.

Binding Domain Characterization of Growth Hormone Secretagogue Receptor.

Background and Objectives: Activation of ghrelin receptor growth hormone secretagogue receptor (GHS-R) by endogenous or synthetic ligands amplifies pulsatile release of growth hormone (GH) and enhances food intake, very relevant to development and growth. GHS-R is a G-protein coupled receptor that has great druggable potential. Understanding the precise ligand and receptor interactions is crucial to advance the application of GHS-R. Materials and Methods: We used radiolabeled ligand-binding assay and growth hormone release assay to assess the binding and functional characteristics of GHS-R to synthetic agonists MK-0677 and GHS-25, as well as to endogenous peptide ligand ghrelin. We analyzed the ligand-dependent activity of GHS-R by measuring aequorin-based [Ca++]i responses. To define a ligand-binding pocket of GHS-R, we generated a series of human/puffer fish GHS-R chimeras by domain swapping, as well as a series of mutants by site-directed mutagenesis. Results: We found that the synthetic ligands have high binding affinity to GHS-R in the in vitro competitive binding assay. Remarkably, the in vivo GH secretagogue activity is higher with the synthetic agonists MK-0677 and GHS-25 than that of ghrelin. Importantly, the activity was completely abolished in GHS-R knockout mice. In GHS-R chimera analysis, we identified the C-terminal region, particularly the transmembrane domain 6 (TM6), to be critical for the ligand-dependent activity. Our site-directed mutagenesis study further revealed that amino acid residues D99 and W276 in GHS-R are essential for ligand binding. Interestingly, critical residues distinctively interact with different ligands, MK-0677 activation depends on E124, while ghrelin and GHS-25 preferentially interact with F279. Conclusion: The ligand-binding pocket of human GHS-R is mainly defined by interactive residues in TM6 and the adjacent region of the receptor. This novel finding in GHS-R binding domains advances the structural/ functional understanding of GHS-R, which will help to select/design better GHS-R agonists/ antagonists for future therapeutic applications.

Association Between Black Race, Clinical Severity, and Management of Acute Pulmonary Embolism: A Retrospective Cohort Study.

Background Existing evidence indicates Black patients have higher incidence of pulmonary embolism (PE) and PE-related mortality compared with other races/ethnicities, yet disparities in presenting severity and treatment remain incompletely understood. Methods and Results We retrospectively queried a multihospital healthcare system for all hospitalizations for acute PE (2012-2019). Of 10 329 hospitalizations, 8743 met inclusion criteria. Black patients (14.3%) were significantly younger (54.6±17.8 versus 63.1±16.6 years; P<0.001) and more female (56.1% versus 51.6%; P=0.003) compared with White patients. Using ordinal regression, Black race was significantly associated with higher PE severity after matching 1:3 on age and sex (1210:3264; odds ratio [OR], 1.08; 95% CI, 1.03-1.14), adjusting for clinical (OR, 1.13; 95% CI, 1.01-1.27), and socioeconomic (OR, 1.05; 95% CI, 1.05-1.35) characteristics. Among intermediate and high-severity PE, Black race was associated with a decreased risk of intervention controlling for the competing risk of mortality and censoring on hospital discharge. This effect was modified by PE severity (P value <0.001), with a lower and higher risk of intervention for intermediate and high-severity PE, respectively. Race was not associated with in-hospital mortality (OR, 0.84; 95% CI, 0.69-1.02). Conclusions Black patients hospitalized with PE are younger with a higher severity of disease compared with White patients. Although Black patients are less likely to receive an intervention overall, this differed depending on PE severity with higher risk of intervention only for life-threatening PE. This suggests nuanced racial disparities in management of PE and highlights the complexities of healthcare inequalities.

Helically arranged cross struts in azhdarchid pterosaur cervical vertebrae and their biomechanical implications.

Azhdarchid pterosaurs, the largest flying vertebrates, remain poorly understood, with fundamental aspects of their palaeobiology unknown. X-ray computed tomography reveals a complex internal micro-architecture for three-dimensionally preserved, hyper-elongate cervical vertebrae of the Cretaceous azhdarchid pterosaur, Alanqa sp. Incorporation of the neural canal within the body of the vertebra and elongation of the centrum result in a "tube within a tube" supported by helically distributed trabeculae. Linear elastic static analysis and linearized buckling analysis, accompanied with a finite element model, reveal that as few as 50 trabeculae increase the buckling load by up to 90%, implying that a vertebra without the trabeculae is more prone to elastic instability due to axial loads. Subsuming the neural tube into the centrum tube adds considerable stiffness to the cervical series, permitting the uptake of heavy prey items without risking damage to the cervical series, while at the same time allowing considerable skeletal mass reduction.

ß Cell GHS-R Regulates Insulin Secretion and Sensitivity.

Growth hormone secretagogue receptor (GHS-R) is widely known to regulate food intake and adiposity, but its role in glucose homeostasis is unclear. In this study, we investigated the expression of GHS-R in mouse pancreatic islets and its role in glycemic regulation. We used Ghsr-IRES-tauGFP mice, with Green Fluorescent Protein (GFP) as a surrogate for GHS-R, to demonstrate the GFP co-localization with insulin and glucagon expression in pancreatic islets, confirming GHS-R expression in ß and α cells. We then generated ß-cell-specific GHSR-deleted mice with MIP-Cre/ERT and validated that GHS-R suppression was restricted to the pancreatic islets. MIP-Cre/ERT;Ghsrf/f mice showed normal energy homeostasis with similar body weight, body composition, and indirect calorimetry profile. Interestingly, MIP-Cre/ERT;Ghsrf/f mice exhibited an impressive phenotype in glucose homeostasis. Compared to controls, MIP-Cre/ERT;Ghsrf/f mice showed lower fasting blood glucose and insulin; reduced first-phase insulin secretion during a glucose tolerance test (GTT) and glucose-stimulated insulin secretion (GSIS) test in vivo. The isolated pancreatic islets of MIP-Cre/ERT;Ghsrf/f mice also showed reduced insulin secretion during GSIS ex vivo. Further, MIP-Cre/ERT;Ghsrf/f mice exhibited improved insulin sensitivity during insulin tolerance tests (ITT). Overall, our results confirmed GHS-R expression in pancreatic ß and α cells; GHS-R cell-autonomously regulated GSIS and modulated systemic insulin sensitivity. In conclusion, ß cell GHS-R was an important regulator of glucose homeostasis, and GHS-R antagonists may have therapeutic potential for Type 2 Diabetes.

Thirty-day readmissions due to Venous thromboembolism in patients discharged with syncope.

A recent study found that approximately 1 in every 6 patients hospitalized for the 1st episode of syncope had an underlying pulmonary embolism (PE). As current guidelines do not strongly emphasize evaluation for PE in the workup of syncope, we hypothesize that there might be a higher rate of 30-day readmission due to untreated venous thromboembolism (VTE). The objective of this study is to measure the 30-day readmission rate due to VTE and identify predictors of 30-day readmission with VTE among syncope patients. We identified patients admitted with syncope with ICD9 diagnoses code 780.2 in the Nationwide Readmission Database (NRD-2013), Healthcare Cost and Utilization Project (HCUP). The 30-day readmission rate was calculated using methods described by HCUP. Logistic-regression was used to identify predictors of 30-day readmission with VTE. Discharge weights provided by HCUP were used to generate national estimates. In 2013, NRD included 207,339 eligible patients admitted with syncope. The prevalence rates of PE and DVT were 1.1% and 1.4%, respectively. At least one syncope associated condition was present in 60.9% of the patients. Among the patients who were not diagnosed with VTE during index admission for syncope (N = 188,015), 30-day readmission rate with VTE was 0.5% (0.2% with PE and 0.4% with DVT). In conclusion, low prevalence of VTE in patients with syncope and extremely low 30-day readmission rate with VTE argues against missed diagnoses of VTE in index admission for syncope. These results warrant further studies to determine clinical impact of work up for PE in syncope patients without risk factors.

Trends of Inpatient Venous Thromboembolism in United States Before and After the Surgeon General's Call to Action.

Venous thromboembolism (VTE) is an important cause of morbidity and mortality in the United States (US). The increasing rates of VTE in the US resulted in the surgeon general issuing a call to action to reduce VTE in 2008. The objective of our study was to analyze the national trends of inpatient VTE in the US from 2004 to 2013 (5 years before and after 2008). We used the dataset National Inpatient Sample, Healthcare Cost and Utilization Project and measured trends of inpatient VTE by annual % change using joinpoint regression software. From 2004 to 2013 the National Inpatient Sample contained data on 78 million hospitalizations (weighted n = 385 million). In these 1.6 million had a diagnosis of VTE (2.0%, weighted n = 7.7 million) including 1.2 million with deep venous thrombosis (DVT) (1.53%, weighted n = 5.9 million) and 588,878 with pulmonary embolism (PE) (0.74%, weighted n = 2.8 million). Joinpoint regression analysis showed that rates of DVT and PE are increasing consistently from 2004 to 2013(1.27% to 1.80% for DVT and 0.52% to 0.92% for PE). The increasing rates of DVT and PE were consistent in all subgroups except few exceptions. In conclusion inpatient VTE rates continue to rise even after 5 years from the surgeon general's a call to action except in certain high-risk patients. Further research is needed to curb the VTE in patients especially among those perceived to be at lower risk of VTE.

Clinical outcomes with unfractionated heparin monitored by anti-factor Xa vs. activated partial Thromboplastin time.

Anti-factor Xa (anti-Xa) monitoring of unfractionated heparin (UFH) is associated with less time to achieve therapeutic anticoagulation compared to the activated partial thromboplastin time (aPTT). However, it is unknown whether clinical outcomes differ between these methods of monitoring. The aim of this research was to compare the rate of venous thrombosis and bleeding events in patients that received UFH monitored by anti-Xa compared to the aPTT. A retrospective review of electronic health records identified adult patients that received UFH given intravenously (IV) for ≥2 days, with either anti-Xa or aPTT monitoring at an academic tertiary care hospital. This was a pre/post study design conducted between January 1 to December 30, 2014 (aPTT), and January 1 to December 30, 2016 (anti-Xa). All UFH adjustments were based on institutional nomograms. The primary outcome was venous thrombosis and the secondary outcome was bleeding, both of which occurred between UFH administration and discharge from the index hospitalization. A total of 2500 patients were in the anti-Xa group and 2847 patients aPTT group. Venous thrombosis occurred in 10.2% vs 10.8% of patients in the anti-Xa and aPTT groups, respectively (P = .49). Bleeding occurred in 33.7% vs 33.6% of patients in the anti-Xa and aPTT groups, respectively (P = .94). Anti-Xa monitoring was not an independent predictor of either outcome in multivariate logistic regression analyses. Our study found no difference in clinical outcomes between anti-Xa and aPTT-based monitoring of UFH IV.

Targeting Peripheral CB1 Receptors Reduces Ethanol Intake via a Gut-Brain Axis.

Endocannabinoids acting on the cannabinoid-1 receptor (CB1R) or ghrelin acting on its receptor (GHS-R1A) both promote alcohol-seeking behavior, but an interaction between the two signaling systems has not been explored. Here, we report that the peripheral CB1R inverse agonist JD5037 reduces ethanol drinking in wild-type mice but not in mice lacking CB1R, ghrelin peptide or GHS-R1A. JD5037 treatment of alcohol-drinking mice inhibits the formation of biologically active octanoyl-ghrelin without affecting its inactive precursor desacyl-ghrelin. In ghrelin-producing stomach cells, JD5037 reduced the level of the substrate octanoyl-carnitine generated from palmitoyl-carnitine by increasing fatty acid ß-oxidation. Blocking gastric vagal afferents abrogated the ability of either CB1R or GHS-R1A blockade to reduce ethanol drinking. We conclude that blocking CB1R in ghrelin-producing cells reduces alcohol drinking by inhibiting the formation of active ghrelin and its signaling via gastric vagal afferents. Thus, peripheral CB1R blockade may have therapeutic potential in the treatment of alcoholism.

Visual control of steering in curve driving.

This pair of studies investigated steering in the absence of continuous visual information. In a driving simulator, participants steered a curving path that was displayed either continuously or intermittently. Optic flow conditions were manipulated to alter the nature of the heading information with respect to the path being steered. Removing or biasing heading information had little effect on steering even during long and frequent path occlusions as long as turn rate was available. This demonstrates that participants can use intermittent views of the path to plan their steering actions and optic flow to accurately update vehicle turns with respect to that path.

The American Society of Hematology (ASH) Medical Educators Institute: a Pilot Faculty Development Project for Hematology Educators.

Clinician educators at academic medical centers often lack the community, mentorship, and faculty development to support their missions around education scholarship and teaching. Inadequate support for clinician educators can lead to professional dissatisfaction and slowed academic advancement. In 2014, ASH conducted a needs assessment of medical school hematology course directors, hematology-oncology fellowship program directors, and other ASH members identified as educators to determine this community's desire for faculty development in medical education. These data furthered the development of an annual faculty development program for hematology educators offering an interactive curriculum and support for an educational scholarly project. The needs assessment indicated that over 70% of respondents would be personally interested in a faculty development opportunity for hematology educators and only 11% had previously participated in such a program. A steering committee designed an intervention blending didactics, interactive small group exercises, webinars, mentorship for a scholarly project, 360-degree feedback for each participant, and a forum to discuss common career development goals. Of 42 applicants, 20 participants were chosen for the inaugural workshop. Following successful execution of the workshop, participants reported significant increase in confidence in the knowledge, skills, and attitudes targeted by the curriculum. A series of follow-up webinars have been developed to deliver additional content not covered during the workshop and to continue mentorship relationships. The curriculum will be further refined based on feedback from faculty and participants. Long-term outcome measurement will include tracking all participants' publications and presentations, time to promotion, and involvement in national medical education initiatives.

Hemostasis testing and therapeutic plasma exchange: Results of a practice survey.

INTRODUCTION: Performing therapeutic plasma exchange (TPE) with albumin replacement decreases coagulation factor and platelet levels. No defined guidelines exist regarding laboratory testing to assess hemostasis in patients undergoing TPE. MATERIALS AND METHODS: A survey to evaluate hemostasis testing with TPE was distributed using online survey software. One response per institution was analyzed based on a hierarchical algorithm, excluding membrane filtration users, resulting in a maximum of 120 respondents per question. Descriptive analysis was performed with results reported as the number and/or frequency (%) of respondents to each question. RESULTS: The practices represented vary by institution type, number of apheresis procedures per year, and performance of TPE on children. Prior to TPE planned with albumin replacement, many respondents obtain laboratory studies for almost all patients (54.9% outpatients and 68.7% inpatients); however, some do not routinely obtain laboratory studies (9.7% outpatients and 4.4% inpatients). Hemoglobin/hematocrit, platelet count, fibrinogen, partial thromboplastin time (aPTT), and international normalized ratio (INR) are obtained prior to all TPE by 62.5%, 53.4%, 31.0%, 18.1%, and 17.7% of respondents, respectively; however, 1.0%, 8.7%, 29.0%, 38.3%, and 35.4%, respectively, do not routinely obtain these studies. Variation was observed in laboratory threshold values for action; the most common reported were hemoglobin/hematocrit <7 g/dL or 21% (31.0%), platelet count <50 × 109 /L (24.1%), fibrinogen <100 mg/dL (65.3%), aPTT >reference range and >1.5 times reference range (tied, 28.1%), and INR >1.5 (20.7%). CONCLUSIONS: Practice variation exists in hemostasis laboratory testing and threshold values for action with TPE. Further studies are needed to determine optimal hemostasis testing strategies with TPE.

Incomplete recovery of cerebral blood flow dynamics in sufficiently treated high blood pressure.

OBJECTIVE: Whether cerebrovascular regulation is different in patients with controlled high blood pressure (HBP) with and without small vessel disease (SVD). METHODS: Sixty-seven healthy controls (mean age ±â€ŠSD, 45 ±â€Š16 years; 30 women, 37 men) and 40 patients (mean age, 64 ±â€Š13 years; 14 women, 26 men) with HBP and different stages of SVD, underwent simultaneous recordings of the spontaneous fluctuations of BP, blood flow velocity (CBFV) in both middle cerebral arteries (MCA), and of end-tidal CO2 (ETCO2). Coherence and transfer function gain and phase between BP and CBFV were assessed in the frequency ranges of VLF (0.02-0.07 Hz), low frequency (0.07-0.15), and high frequency (>0.15). BP SD indicated BP variability (BPV). RESULTS: In controls (BP, 86 ±â€Š13 mmHg; ETCO2, 39 ±â€Š4 mmHg; BPV, 15 ±â€Š6 mmHg), gain, phase and coherence were not age-dependent in simple or a multiple regression models. BPV correlated significantly in both MCAs with gain in low frequency and high frequency, and with phase in VLF and high frequency. In patients (BP, 91 ±â€Š16 mmHg, ETCO2, 39 ±â€Š4 mmHg, BPV 18 ±â€Š5 mmHg), only gain showed some differences between different SVD groups. Comparing all patients with 25 controls of similar age and sex, patients exhibited significantly (P < 0.05-P < 0.005): increased coherence and gain in VLF, decreased phase in VLF and low frequency, correlations between BPV with phase in low frequency (left) and with gain in VLF (left) and in high frequency (left and right). CONCLUSION: Phase seems an age independent autoregulatory index. In controlled HBP, CBF regulation is degraded at longlasting CBF changes; BPV effects lose their physiological bilateral distribution.

Hemostasis management and therapeutic plasma exchange: Results of a practice survey.

BACKGROUND: Patients undergoing therapeutic plasma exchange (TPE) may present with risks for hemorrhage or thrombosis. Use of replacement fluids devoid of coagulation factors will decrease factor levels and platelet levels. There are no established guidelines for hemostasis management in these situations. MATERIALS AND METHODS: A survey to evaluate current hemostasis management practice during TPE was conducted using online survey software. One response per institution was analyzed based on a hierarchical algorithm, excluding membrane filtration users, resulting in a maximum of 107 respondents. Descriptive analysis was performed with results reported as the number and frequency (%) of respondents to each question. RESULTS: Apheresis Medicine physicians, alone (59.4%) or jointly with the requesting provider (29.2%), choose the replacement fluid. Based on a theoretical patient case receiving five TPEs approximately every other day, the percent of respondents who would use albumin with or without normal saline was 94.7% with no history of a bleeding or clotting disorder, 1.1% with active bleeding, and 8.8% with hypofibrinogenemia (<100 mg/dL) due to recent TPE. More respondents would use albumin with or without normal saline for replacement fluid when a minor invasive procedure (49.5%) vs a major surgery (8.9%) was performed 1 day before TPE. Replacement fluid selection varied among respondents for several other clinical conditions. The most frequent use for cryoprecipitate by respondents (14.3%) was hypofibrinogenemia. CONCLUSIONS: These survey results demonstrate wide interinstitutional variation in replacement fluid selection to manage hemostasis in patients undergoing TPE. Further studies are needed to guide optimal hemostasis management with TPE.

Apixaban or Rivaroxaban Versus Warfarin for Treatment of Submassive Pulmonary Embolism After Catheter-Directed Thrombolysis.

BACKGROUND: Little data exist on the use of direct oral anticoagulant (DOAC) factor Xa inhibitors for submassive pulmonary embolism (PE) after catheter-directed thrombolysis (CDT). The objective of this evaluation was to determine whether the transition from parenteral anticoagulation to DOACs for submassive PE after CDT would decrease hospital length of stay (LOS) compared to warfarin. METHODS: A retrospective review of patients diagnosed with submassive PE who underwent CDT was conducted from January 1, 2012, to February 28, 2017. Hospital LOS and major and minor bleeding events were recorded during hospitalization and at 90 days. RESULTS: Sixty-two patients met the inclusion criteria, 36 in warfarin group and 26 in the DOAC group. Overall, patients receiving rivaroxaban or apixaban had a shorter median hospital LOS compared to warfarin (4.0 vs 6.1 days, P = .002). In the multivariate regression analysis, administration of DOAC was an independent predictor of decreased hospital LOS, ß: -2.1, 95% confidence interval (-3.5 to -0.7). CONCLUSION: Among patients with submassive PE, initiation of a DOAC shortly after CDT may result in a decreased hospital LOS compared to parenterally bridged warfarin.