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.

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.

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.

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.

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.

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.

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.

Performance of Anti-Factor Xa Versus Activated Partial Thromboplastin Time for Heparin Monitoring Using Multiple Nomograms.

The purpose of this study was to compare the performance of anti-factor Xa concentration versus activated partial thromboplastin time (aPTT) monitoring with multiple indication-specific heparin nomograms. This was a prospective, nonrandomized study with historical control at a large academic medical center. A total of 201 patients who received intravenous heparin in the cardiology units were included. The prospective cohort included patients (n = 101) with anti-factor Xa (anti-Xa) monitoring, and the historical control group included patients (n = 100) who had aPTT monitoring. Patients in the prospective group had both anti-Xa and aPTT samples drawn, but anti-Xa was used for dosing adjustment. The anti-Xa cohort achieved a significantly faster time to therapeutic range ( P < .01) and required fewer dose adjustments per 24-hour period compared to the aPTT control ( P = .01). Results were consistent across heparin nomograms. The overall discordance rate between the 2 tests was 49%. No significant differences in clinical outcomes were observed. In summary, anti-Xa monitoring improved the time to therapeutic anticoagulation and led to fewer dose adjustments compared to the aPTT with multiple indication-based heparin nomograms.

Thrombosis-associated antifibrinogen IgG1 κ impairs fibrin polymerization and enhances platelet activation.

The present study extends our previous investigation of circulating antibody/fibrinogen/C1q complexes (FgIgC) associated with thrombosis in a heterophenotypic AαR16C proband, by focusing on the molecular and functional characteristics of the FgIgC, isolated by cryoprecipitation, FgIgC components were demonstrated by SDS-PAGE and by rotary shadowing electron microscopy. Affinity chromatography was used to isolate IgG and fibrinogen from FgIgC. Thrombin-induced clots were examined by scanning electron microscopy and turbidity measurements. IgG/fibrinogen binding was measured by ELISA. Fibrinogen Aα1-19 peptides, cleaved by thrombin from fragment N-DSK, were examined by mass spectrometry. Clot stiffness, platelet release of P-selectin, and fibrinogen self-assembly were assessed by thromboelastography, flow cytometry, and atomic force microscopy, respectively. The FgIgC effects included the following: increased P-selectin release from gel-sieved platelets, finer fiber networks and decreased stiffness of its clots, and marked inhibition of fibrinogen self-assembly. The abnormal proband fibrinogen structure displayed phosphorylated AαR16C-AαR16C homodimers and AαR16C-glutathione heterodimers. ELISA measurements disclosed pronounced binding by proband fibrinogen to proband IgG, which was blocked by the IgG's Fab fragment and by proband, but not by normal plasmic fragment E1. There was appreciable, but much weaker, binding to normal fibrinogen, to its fragments E1, and D1, and to homodimeric AαR16C fibrinogen. The antibody's primary target epitope included heterodimeric AαR16C-glutathione; a secondary epitope resided in the D region. Moreover, both the enhanced platelet activation (i.e. increased P-selectin release induced by FgIgC) and the highly phosphorylated FpA (i.e. resulting in its accelerated release by thrombin) may have contributed to the thrombotic diathesis.

Clinical effectiveness and safety outcomes associated with prothrombin complex concentrates.

Prothrombin complex concentrates (PCCs) are indicated for urgent reversal of warfarin and used for reversal of novel oral anticoagulants, in patients with acute major bleeding or need for an urgent procedure. The research goal was to evaluate effectiveness and safety outcomes with PCC usage at our institution. A retrospective review of electronic medical records identified patients that received a PCC commercially available in the United States (KCentra(®) or Profilnine(®)) at twelve hospitals in a tertiary care health system from July 1, 2013 to April 30, 2014. A total of 193 patients received PCC, of which 184 patients received four-factor PCC. The patient population was 48 % male and 75 % Caucasian, with a mean age of 73 years old. Clinical outcomes of interest included time to achieve a target INR ≤1.3, time to Hgb >7 g/dL, and incidence of thromboembolism. A total of 143 patients were on warfarin (74.1 %) at baseline, whereas 18 patients (9.3 %) were taking a novel anticoagulant. Target INR of ≤1.3 was achieved in 125 patients (65.8 %), within a median time of 8.03 h (IQR 3.38-34.07). Among patients with a baseline Hgb <7 g/L (n = 13), the median time to Hgb >7 g/dL was 8.48 h (IQR 6.95-13.00). Eight patients (4.1 %) developed an acute venous thromboembolism following PCC administration. INR reversal was achieved in approximately two-thirds of patients, with a low incidence of venous thromboembolism. Four-factor PCC is a viable alternative to plasma.

Evaluation of Risk Factors for Rectus Sheath Hematoma.

Rectus sheath hematoma (RSH) develops due to rupture of epigastric arteries or the rectus muscle. Although RSH incidence rate is low, it poses a significant diagnostic dilemma. We evaluated the risk factors for RSH, its presentation, management, and outcomes for 115 patients hospitalized with confirmed RSH by computed tomography scan between January 2005 and June 2009. More than three-fourth (77.4%) of the patients were on anticoagulation therapy, 58.3% patients had chronic kidney disease (CKD) stage ≥3, 51.3% had abdominal injections, 41.7% were on steroids/immunosuppressant therapy, 37.4% had abdominal surgery/trauma, 33.9% had cough, femoral puncture was performed in 31.3% of patients, and 29.5% were on antiplatelet therapy. Rectus sheath hematoma was not an attributable cause in any of the 17 deaths. Mortality was significantly higher in patients with CKD stage ≥3 (P = .03) or who required transfusion (P = .007). Better understanding of RSH risk factors will facilitate early diagnoses and improve management.

Plasma from chronic liver disease subjects exhibit differential ability to generate thrombin.

Liver fibrosis in chronic liver disease (CLD) results in complex alterations in procoagulant and anticoagulant proteins. Although an elevated international normalized ratio (INR) is a prominent feature of progressive fibrosis, the utility of the INR to accurately reflect the net effect of these changes on the coagulation system is uncertain. In subjects with CLD, elevated INRs have been observed in both bleeding and thrombotic complications, suggesting limitations of the INR in characterizing the coagulation status. Unlike the INR, which is preferentially sensitive to the extrinsic pathway, the direct measurement of thrombin generation better captures the global coagulation cascade. We conducted a pilot study measuring the INR, chromogenic factor X and thrombin generation in CLD subjects and compared them with control subjects and subjects on warfarin anticoagulation. We observed a large interquartile range in thrombin generation among compensated CLD subjects across a narrow INR range, suggesting that the INR is a suboptimal surrogate measure of thrombin generation in CLD subjects.

Chronic myelogenous leukemia in eastern Pennsylvania: an assessment of registry reporting.

BACKGROUND: Chronic myelogenous leukemia (CML) has been reportable to the Pennsylvania Cancer Registry (PCR) since the 1980s, but the completeness of reporting is unknown. This study assessed CML reporting in eastern Pennsylvania where a cluster of another myeloproliferative neoplasm was previously identified. METHODS: Cases were identified from 2 sources: 1) PCR case reports for residents of Carbon, Luzerne, or Schuylkill County with International Classification of Diseases for Oncology, Third Edition (ICD-O-3) codes 9875 (CML, BCR-ABL+), 9863 (CML, NOS), and 9860 (myeloid leukemia) and date of diagnosis 2001-2009, and 2) review of billing records at hematology practices. Participants were interviewed and their medical records were reviewed by board-certified hematologists. RESULTS: PCR reports included 99 cases coded 9875 or 9863 and 9 cases coded 9860; 2 additional cases were identified by review of billing records. Of the 110 identified cases, 93 were mailed consent forms, 23 consented, and 12 medical records were reviewed. Hematologists confirmed 11 of 12 reviewed cases as CML cases; all 11 confirmed cases were BCR/ABL positive, but only 1 was coded as positive (code 9875). CONCLUSIONS: Very few unreported CML cases were identified, suggesting relatively complete reporting to the PCR. Cases reviewed were accurately diagnosed, but ICD-0-3 coding often did not reflect BCR-ABL-positive tests. Cancer registry abstracters should look for these test results and code accordingly.

Outcomes of platelet transfusion in patients with thrombotic thrombocytopenic purpura: a retrospective case series study.

Current guidelines advise against the transfusion of platelets in patients with thrombotic thrombocytopenic purpura (TTP) except in cases of life-threatening hemorrhage. We conducted a retrospective medical chart review to examine the outcomes of patients with TTP who received platelet transfusion at our institution from September 2002 to September 2012. A search for "thrombotic thrombocytopenic purpura" in the discharge summary identified 233 patients, out of which only 15 patients had TTP and received platelet transfusion. Primary outcomes were death due to any cause, myocardial infarction, ischemic stroke, coma, seizure, or worsening neurologic status within 24 h of platelet transfusion. Secondary outcomes included bleeding and worsening thrombocytopenia. No adverse outcomes occurred within 24 h of platelet transfusion. Two patients experienced bleeding following renal biopsy despite having platelet counts of greater than 50,000/µl and receiving one pack of pooled platelets prior to the procedures. The response to transfusion was variable. In general, platelet transfusion was not detrimental in this population; however, the efficacy is uncertain.

A Review of and Recommendations for the Management of Patients With Life-Threatening Dabigatran-Associated Hemorrhage: A Single-Center University Hospital Experience.

Dabigatran is an oral direct thrombin inhibitor that is approved for the prevention of stroke and systemic embolism in nonvalvular atrial fibrillation. Dabigatran has several advantages over warfarin including predictable pharmacokinetics and pharmacodynamics which eliminates the need for routine laboratory monitoring, superiority over warfarin in preventing stroke, or systemic embolism without having an increased risk of bleeding. However, as with any anticoagulant, there remains a real chance of bleeding, including major or life-threatening hemorrhage. Many physicians feel comfortable managing bleeding complications on older anticoagulants like warfarin and heparin, due to extensive experience with the medications along with antidotes to reverse their effects as well as established protocols for treating anticoagulant-associated hemorrhage. However, most physicians have limited clinical experience with dabigatran, there is no specific antidote for dabigatran reversal and there is a paucity of protocols, guidelines, and recommendations for how to manage dabigatran-associated hemorrhage. In this review, we present a case series of patients admitted to our institution for management of bleeding while receiving dabigatran. We retrospectively reviewed these cases to evaluate the efficacy and rationale of the various anticoagulation reversal strategies employed in the context of the existing evidence found in the literature. Specific focus is placed on the therapies utilized and the coagulation studies used to manage these patients.

A case of thrombotic microangiopathy/microangiopathies.

We report a case of Streptococcus pneumonia sepsis-associated disseminated intravascular coagulation (DIC) with features of acute renal failure and microvascular thrombosis characterized by skin purpura and bilateral foot necrosis. The persistence of laboratory features of microangiopathic hemolytic anemia despite aggressive correction of DIC-associated coagulopathy suggests the possibility of an additional concomitant microangiopathic process. Here, we discuss the management and diagnostic approach, particularly highlighting the difficulties in making a definitive diagnosis. Although unconfirmed, our differentials include the concomitant process of sepsis-induced DIC occurring together with an indeterminate form of plasmapheresis and plasma exchange-responsive thrombotic microangiopathy, processes which are previously believed to be mutually exclusive.