Factor product utilization and health outcomes in patients with haemophilia A and B on extended half-life concentrates: A Canadian observational study of real-world outcomes.

INTRODUCTION: Recombinant factors VIII and IX Fc (rFVIIIFc/rFIXFc) became available in Canada in 2016 and were the only extended half-life (EHL) factor concentrates available in Canada until 2018. OBJECTIVES: We aim to describe the change in product utilization in Canadians who switched to rFVIIIFc/rFIXFc. METHODS: This prospective and retrospective cohort study enrolled males aged ≥6 years with moderate or severe haemophilia who switched to rFVIIIFc/rFIXFc and those who remained on standard half-life (SHL) between 2016 and 2018. Factor utilization and annualized bleeding rates (ABR) were collected at baseline, 1-year and 2-years. Due to low prospective enrolment (n = 25 switchers), prospective and retrospective data were pooled. RESULTS: 125 switchers (93 rFVIIIFc, 32 rFIXFc) and 33 non-switchers were included. The median age was 17 (rFVIIIFc) and 38 years (rFIXFc). Prior to switch, over 80% were on prophylaxis. There was a statistically significant reduction in the prescribed weekly prophylactic dose after the switch to rFVIIIFc/rFIXFc for all age groups, with a corresponding reduction (15-16%) in actual annualized FIX utilization in switchers (combined adults and children) to rFIXFc, and a smaller non-significant reduction in actual annualized FVIIII utilization (7%) in children who switched to rFVIIIFc. A significant reduction in the median ABR was only observed in children who switched to rFVIIIFc, but not in adults who switched to rFVIIIFc or rFIXFc. CONCLUSION: Switching from SHL to EHL products led to a small reduction in factor utilization, while preserving a low ABR in children and adults with haemophilia. Further patient-reported outcomes data will further elucidate the role of EHL in the haemophilia landscape.

Complications and functional outcomes after transolecranon distal humerus fracture.

BACKGROUND: Transolecranon distal humerus fractures are uncommon injuries. This is the first multipatient case series to describe outcomes and complications following transolecranon distal humerus fractures in the adult population. METHOD: Design: retrospective; setting: single level 1 trauma center; patients/participants: 16 patients; intervention: surgical management of transolecranon distal humerus fracture; main outcome measurement: Disabilities of the Arm, Shoulder, and Hand (DASH) questionnaire after a minimum of 12 months. RESULTS: A total of 16 patients with open (n = 12) or closed (n = 4) transolecranon distal humerus fractures were identified. Nine female and 7 male patients with a mean age of 47 years were included. Mechanisms of injury included motor vehicle collisions (n = 3), motorcycle crashes (n = 4), ground-level falls (n = 3), falls from height (n = 4), train collision (n = 1), and an industrial accident (n = 1). Seven patients (44%) presented with nerve injury. Patients underwent open reduction with internal fixation (n = 15), external fixation (n = 6), or both (n = 5). Additional surgeries were ultimately required in 11 patients (69%), with a mean of 3 surgeries to manage each patient's elbow injuries. All patients returned for at least 3 clinical follow-up visits; mean clinical follow-up was 15.8 months and mean radiographic follow-up was 12.3 months. Complications were observed in 15 patients (94%). Eleven patients (69%) had limited range of motion with a flexion arc of less than 100° at their last clinic visit. Seven patients (44%) developed deep wound infections requiring repeat débridement and intravenous antibiotics. Implant removal was performed in 10 patients (62.5%) because of infection (n = 5), symptomatic hardware (n = 4), or device failure (n = 1). Heterotopic ossification was seen in 8 patients (50%) and post-traumatic arthrosis in 4 (25%). Two patients (12.5%) required flap reconstruction for soft tissue defects. Nonunion occurred in 7 patients (44%). DASH scores were obtained for 10 patients (62.5%) at a mean of 3.8 years after injury. The mean DASH score was 40.2, ranging from 4.2 to 76.5. Among respondents, 7 (70%) were able to resume working, with an average DASH work module score of 25. CONCLUSION: Management of transolecranon distal humerus fractures remain a challenge for orthopedic surgeons. Complication rates, including deep infection and nonunion, are high, with frequent long-term functional limitations posed to the patient, as evidenced by DASH scores.

Identification of hypercoagulability with thrombelastography in patients with hip fracture receiving thromboprophylaxis.

Background: Venous thromboembolism (VTE) is the second most common complication after hip fracture surgery. We used thrombelastography (TEG), a whole-blood, point-of-care test that can provide an overview of the clotting process, to determine the duration of hypercoagulability after hip fracture surgery. Methods: In this prospective study, consecutive patients aged 51 years or more with hip fractures (trochanteric region or neck) amenable to surgical treatment who presented to the emergency department were eligible for enrolment. Thrombelastography, including calculation of the coagulation index (CI) (combination of 4 TEG parameters for an overall assessment of coagulation) was performed daily from admission until 5 days postoperatively, and at 2 and 6 weeks postoperatively. All patients received 28 days of thromboprophylaxis. We used single-sample t tests to compare mean maximal amplitude (MA) values (a measure of clot strength) to the hypercoagulable threshold of greater than 65 mm, a predictor of in-hospital VTE. Results: Of the 35 patients enrolled, 11 (31%) were hypercoagulable on admission based on an MA value greater than 65 mm, and 29 (83%) were hypercoagulable based on a CI value greater than 3.0; the corresponding values at 6 weeks were 23 (66%) and 34 (97%). All patients had an MA value greater than 65 mm at 2 weeks. Patients demonstrated normal coagulation on admission (mean MA value 62.2 mm [standard deviation (SD) 6.3 mm], p = 0.01) but became significantly hypercoagulable at 2 weeks (mean 71.6 mm [SD 2.6 mm], p < 0.001). There was a trend toward persistent hypercoagulability at 6 weeks (mean MA value 66.2 mm [SD 3.8 mm], p = 0.06). Conclusion: More than 50% of patients remained hypercoagulable 6 weeks after fracture despite thromboprophylaxis. Thrombelastography MA thresholds or a change in MA over time may help predict VTE risk; however, further study is needed.

Contexte: La thromboembolie veineuse (TEV) est la deuxième complication la plus courante après une chirurgie pour fracture de la hanche. Nous avons eu recours à la thromboélastographie, un test de sang total effectué au point d'intervention et donnant une idée du processus de coagulation, pour évaluer la durée de l'hypercoagulabilité à la suite d'une chirurgie pour fracture de la hanche. Méthodes: Cette étude prospective a été menée auprès de patients consécutifs admissibles de 51 ans et plus qui se sont présentés à l'urgence pour une fracture de la hanche (région trochantérienne ou col du fémur) pouvant faire l'objet d'un traitement chirurgical. Une thromboélastographie (TEG), qui comprenait le calcul de l'indice de coagulation (IC) [combinaison de 4 paramètres du TEG permettant une évaluation globale de la coagulation], a été réalisée chaque jour, de l'admission au cinquième jour postopératoire, de même qu'à 2 et à 6 semaines postopératoires. Tous les patients ont suivi une thromboprophylaxie de 28 jours. Nous avons réalisé des tests t pour échantillon unique afin de comparer l'amplitude maximale (AM) moyenne (une mesure de la résistance d'un caillot) au seuil d'hypercoagulabilité de plus de 65 mm, un prédicteur de TEV à l'hôpital. Résultats: Des 35 patients recrutés, 11 (31 %) présentaient une hypercoagulabilité à l'admission selon une AM supérieure à 65 mm, et 29 (83 %) présentaient une hypercoagulabilité selon un IC supérieur à 3,0; les valeurs correspondantes à 6 semaines étaient de 23 (66 %) et de 34 (97 %), respectivement. Tous les patients avaient une AM de plus de 65 mm à 2 semaines. Dans l'ensemble, les patients avaient une coagulation normale à l'admission (AM moyenne 62,2 mm [écart type (E.T.) 6,3 mm], p = 0,01), mais présentaient une hypercoagulabilité importante à 2 semaines (moyenne 71,6 mm [E.T. 2,6 mm], p < 0,001). L'hypercoagulabilité avait tendance à persister à 6 semaines (AM moyenne 66,2 mm [E.T. 3,8 mm], p = 0,06). Conclusion: Malgré la thromboprophylaxie, plus de 50 % des patients présentaient toujours une hypercoagulabilité 6 semaines après leur fracture. Les seuils d'AM à la thromboélastographie et les changements de l'AM au fil du temps pourraient aider à prédire le risque de TEV, mais d'autres études sur le sujet sont nécessaires.

Bleeding assessment in haemophilia carriers-High rates of bleeding after surgical abortion and intrauterine device placement: A multicentre study in China.

INTRODUCTION: An increased bleeding tendency has been shown in female haemophilia carriers compared to healthy females. Bleeding assessment tools (BATs) have mainly been performed in western cultures. It is unclear how they perform in populations with different healthcare, health/wellness concepts and awareness, as well as family planning practices. AIM: To (a) describe and compare the bleeding symptoms in carriers with healthy females, particularly for bleeding after surgical abortion and intrauterine device (IUD) placement which are performed frequently for family planning in China; (b) quantify scores of International Society on Thrombosis and Haemostasis Bleeding Assessment Tool (ISTH-BAT) and Chinese-BAT (C-BAT) developed to include surgical abortion and IUD placement as separate categories in Chinese haemophilia carriers; (c) correlate bleeding scores (BS) with factor levels. METHODS: We conducted a multicentre, cross-sectional study on obligate haemophilia carriers and healthy controls using ISTH-BAT and C-BAT. RESULTS: We enrolled 125 haemophilia carriers and 106 controls. Carriers, compared to controls, had significantly higher median BS (3 vs 1 by both ISTH-BAT and C-BAT) and lower factor level (63.5 vs 101.8 IU/dL). Bleeding after surgical abortion and IUD placement was significantly associated with carrier status. Bleeding scores from neither ISTH-BAT nor C-BAT showed significant correlation with factor levels. CONCLUSION: Haemophilia carriers in China experienced abnormal bleeding. Unique to the Chinese carriers is significant bleeding after surgical abortion (3rd highest incidence of bleeding symptom) and IUD placement (4th highest). However, both ISTH-BAT and C-BAT exhibited no correlation between BS and factor levels in this population and neither could identify carriers with low factor level (of <50 IU/dL).

Fondaparinux cross-reactivity in heparin-induced thrombocytopenia successfully treated with high-dose intravenous immunoglobulin and rivaroxaban.

HIT, a prothrombotic disorder caused by heparin-dependent antibodies, is often treated with fondaparinux, usually with good outcomes. A 70-year-old female developed severe HIT (platelet count, 25 × 109/L) post-glioblastoma resection during heparin thromboprophylaxis, complicated by disseminated intravascular coagulation (DIC) and symptomatic lower-limb deep-vein thrombosis (DVT). Despite therapeutic-dose fondaparinux, thrombocytopenia/hypofibrinogenemia persisted, with new symptomatic catheter-associated upper-extremity DVT. This clinical picture could be explained by autoimmune HIT (aHIT) refractory to fondaparinux or by fondaparinux cross-reactivity, so high-dose intravenous immunoglobulin (IVIG) was given (to treat possible aHIT) and fondaparinux switched to rivaroxaban, with subsequent clinical recovery. In vitro studies revealed strong fondaparinux cross-reactivity, without aHIT antibodies. Moreover, the patient's serotonin-release assay became negative post-IVIG, suggesting in-vivo inhibition of HIT antibody-induced platelet activation. Our case illustrates fondaparinux cross-reactivity in HIT manifesting as persisting thrombocytopenia, new thrombosis, and DIC, with successful rivaroxaban treatment, adding to emerging data that oral factor Xa inhibitors are efficacious for treating HIT.

Non-native honey bees disproportionately dominate the most abundant floral resources in a biodiversity hotspot.

Most plant-pollinator mutualisms are generalized. As such, they are susceptible to perturbation by abundant, generalist, non-native pollinators such as the western honey bee ( Apis mellifera), which can reach high abundances and visit flowers of many plant species in their expansive introduced range. Despite the prevalence of non-native honey bees, their effects on pollination mutualisms in natural ecosystems remain incompletely understood. Here, we contrast community-level patterns of floral visitation by honey bees with that of the diverse native pollinator fauna of southern California, USA. We show that the number of honey bees visiting plant species increases much more rapidly with flower abundance than does that of non-honey bee insects, such that the percentage of all visitors represented by honey bees increases with flower abundance. Thus, honey bees could disproportionately impact the most abundantly blooming plant species and the large numbers of both specialized and generalized pollinator species that they sustain. Honey bees may preferentially exploit high-abundance floral resources because of their ability to recruit nest-mates; these foraging patterns may cause native insect species to forage on lower-abundance resources to avoid competition. Our results illustrate the importance of understanding foraging patterns of introduced pollinators in order to reveal their ecological impacts.

Emergency management of patients with bleeding disorders: Practical points for the emergency physician.

Emergency department (ED) physicians are often the first point of contact for patients who present with bleeding symptoms. Work up and management of bleeding in the emergency room can be a daunting task as it requires: (1) accurate diagnosis of the bleeding cause, of which there is long list of common and rare etiologies (2); appropriate investigations and interpretation of the results; and (3) timely management of bleeding symptoms to prevent limb- or life-threatening complications. Crucial to the management of a bleeding patient is a thorough yet focused history exploring bleeding symptoms, medications/drugs (anticoagulants, antiplatelets), mechanism of trauma/injury, personal and family history of diagnosed bleeding disorders or bleeding symptoms and recognizing acuity and severity of bleeding that requires immediate intervention. Physical examination should focus on signs of mucocutaneous versus deep tissue or joint bleeding and assessing for structural lesions that may contribute to bleeding symptoms in patients with known bleeding diathesis. In patients with diagnosed bleeding disorders, emergency care cards will usually outline the initial treatment (e.g. clotting factor replacement, DDAVP) which should be administered before pursuing investigations/imaging studies. Special attention must be paid to the patient with recurrent or unexplained bleeding, or unexplained coagulation studies. There should be a low threshold to consult hematology in these cases and involvement of hematology early in managing patients with bleeding disorders to improve outcomes. This paper is directed toward emergency physicians, pediatricians, and general internists and will highlight key concepts in the primary care and work up of diagnosed and undiagnosed bleeding disorders requiring urgent treatment.

Desmopressin in non-severe haemophilia A: Test-response and clinical outcomes in a single Canadian centre review.

INTRODUCTION: Desmopressin is an effective haemostatic agent for patients with non-severe haemophilia A; however, response may differ between patients of similar severity. Responsiveness is classified based on various cut-off values for plasma levels of FVIII post-desmopressin administration. Patients may be classified differently depending on the values chosen. AIM: To classify desmopressin response in non-severe haemophilia A patients with respect to current test-response definitions. Also, to characterize relationships between test response and clinical outcome of desmopressin use. METHODS: Current desmopressin test-response definitions were obtained from the literature. We adopted peak FVIII level (at 1 hour post-administration) ≥50 IU/dL and <20 IU/dL as complete and no response, respectively, thereby satisfying most reported definitions. Test-responses and clinical outcomes of use between 2007 and 2017 for adult mild/moderate haemophilia A patients were reviewed and correlated. RESULTS: All patients classified as complete responders (n = 31; peak FVIII ≥50 IU/dL) and the majority of partial responders (n = 11; peak FVIII ≥20 to <50 IU/dL) had good clinical outcomes after desmopressin use for a variety of bleeding episodes and procedures. Two non-responders (peak FVIII <20 IU/dL) given desmopressin for minor bleeding/procedures also had good clinical outcomes. One patient with a partial test-response (peak FVIII 23 IU/dL) required additional factor concentrate to achieve haemostasis. CONCLUSIONS: Based on our review, we suggest that the determination of desmopressin responsiveness should consider both the change in plasma FVIII levels as well as clinical outcomes associated with prior therapeutic use.

Inherited platelet functional disorders: General principles and practical aspects of management.

Platelets are a critical component for effecting hemostasis and wound healing. Disorders affecting any platelet pathway mediating adhesion, activation, aggregation and procoagulant surface exposure can result in a bleeding diathesis. Specific diagnosis even with advanced techniques which are unavailable to most centers is often difficult. Inherited platelet function disorders therefore represent a heterogeneous and complex collection of disorders with a spectrum of bleeding severity, from relatively mild (and easily missed or misdiagnosed) to severe bleeding phenotype with salient diagnostic features. We advocate the use of bleeding assessment tools to help identification of patients and more importantly for assessment of individual patient bleeding phenotype to guide management decisions for treating and preventing bleeding. The complex management of these patients is best coordinated in a multidisciplinary comprehensive care clinic setting expert in managing bleeding disorders and associated complications, with particular attention to the physical and psychosocial health of patients and their families. Depending on the bleeding phenotype, the location and severity of bleeding, and the nature of an invasive procedure, available treatment modalities range from conservative measures using local pressure, topical thrombin, fibrin sealant, antifibrinolytics etc. to the use of systemic haemostatics such as desmopressin (DDAVP), platelets and recombinant human activated factor VII (rFVIIa). This review will provide opinions on the practical aspects and general management of inherited platelet function disorders, with discussion on the mechanism of action, and the pros and cons of various hemostatic agents. Finally, the prospect of curative treatment for patients with severe bleeding phenotype refractory to available treatments and with poor quality of life will be briefly discussed.

Premature changes in trabecular and cortical microarchitecture result in decreased bone strength in hemophilia.

Low bone density is a growing concern in aging men with hemophilia and may result in high-morbidity fragility fractures. Using high-resolution peripheral quantitative computed tomography (HR-pQCT), we demonstrate low trabecular and cortical bone density contributing to lower volumetric bone mineral density (BMD) at both distal radius and tibia in patients with hemophilia compared with age- and sex-matched controls. The low trabecular bone density found in hemophilia is attributed to significantly decreased trabecular number and increased separation; the lower cortical bone density results from thinner cortices, whereas cortical porosity is maintained. Microfinite element analysis from three-dimensional HR-pQCT images demonstrates that these microarchitectural deficits seen in patients with hemophilia translate into significantly lower estimated failure load (biomechanical bone strength) at the distal tibia and radius when compared with controls. In addition, an inverse association of joint score with BMD and failure load suggests the negative role of hemophilic arthropathy in bone density loss.

A longitudinal view of factors that influence the emotional well-being of family caregivers to individuals with heart failure.

OBJECTIVES: Caring for community-residing patients with heart failure can affect caregivers' emotional wellbeing. However, few studies have examined caregivers' well-being longitudinally, or identified factors associated with positive and negative outcomes. The objective of this longitudinal cohort study was to examine changes in caregivers' well-being over time, and to identify patient and caregiver factors associated with positive and negative outcomes. METHOD: Fifty caregiver/heart failure patient dyads were recruited from an acute care facility and followed in the community. All participants completed surveys at hospital admission and 3, 6 and 12 months later. Caregivers completed assessments of depression symptoms and positive affect and standardized measures to capture assistance provided, mastery, personal gain, social support, participation restriction, and patients' behavioral and psychological symptoms. From patients, we collected demographic characteristics and health-related quality of life. Individual Growth Curve modelling was used to analyze the data. RESULTS: Caregivers' negative and positive emotions remained stable over time. Depression symptoms were associated with higher participation restriction in caregivers. Positive affect was associated with more personal gain and more social support. Patients' health-related quality of life and their behavioral and psychological symptoms were not significantly associated with caregivers' emotional outcomes. CONCLUSION: Interventions should be offered based on caregivers' needs rather than patients' health outcomes, and should focus on fostering caregivers' feelings of personal gain, assisting them with securing social support, and engaging in valued activities.

Acquired von Willebrand syndrome: von Willebrand factor propeptide to von Willebrand factor antigen ratio predicts remission status.

We investigated a case of acquired von Willebrand syndrome (AVWS) secondary to a nonneutralizing anti-von Willebrand factor (VWF) antibody associated with an autoimmune disorder. At diagnosis, VWF activity (VWF:Act), antigen (VWF:Ag), multimers, and factor VIII coagulant activity were virtually absent. VWF propeptide (VWFpp) was elevated with an infinitely high VWFpp to VWF:Ag ratio (VWFpp:Ag) consistent with rapid VWF clearance. Immunosuppressive treatment resulted in phenotypic remission 1 with normalization of VWF/factor VIII levels and multimer pattern. However, VWFpp:Ag remained elevated (∼2× normal), consistent with ongoing VWF clearance by the remaining anti-VWF antibody still present by enzyme-linked immunosorbent assay. This suggests that increased VWF secretion was compensating for the incomplete remission state. Relapse occurred when VWFpp:Ag was again infinitely high, with associated decreased VWFpp but unchanged anti-VWF titers; switching the balance to favor VWF clearance over secretion. Complete remission with undetectable anti-VWF occurred only when VWFpp:Ag was normal. This case of relapsing-remitting AVWS demonstrates the use of VWFpp:Ag for predicting remission status.

Individualized prophylaxis for optimizing hemophilia care: can we apply this to both developed and developing nations?

Prophylaxis is considered optimal care for hemophilia patients to prevent bleeding and to preserve joint function thereby improving quality of life (QoL). The evidence for prophylaxis is irrefutable and is the standard of care in developed nations. Prophylaxis can be further individualized to improve outcomes and cost effectiveness. Individualization is best accomplished taking into account the bleeding phenotype, physical activity/lifestyle, joint status, and pharmacokinetic handling of specific clotting factor concentrates, all of which vary among individuals. Patient acceptance should also be considered. Assessment tools (e.g. joint status imaging and function studies/scores, QoL) for determining and monitoring risk factors and outcome, as well as population PK profiling have been developed to assist the individualization process. The determinants of optimal prophylaxis include (1) factor dose/dosing frequency, hence, cost/affordability (2) bleeding triggers (physical activity/lifestyle, chronic arthropathy and synovitis) and (3) bleeding rates. Altering one determinant results in adjustment of the other two. Thus, the trough level to protect from spontaneous bleeding can be increased in patients who have greater bleeding risks; and prophylaxis to achieve zero joint bleeds is achievable through optimal individualization. Prophylaxis in economically constrained nations is limited by the ill-affordability of clotting factor concentrates. However, at least 5 studies on children and adults from Thailand, China and India have shown superiority of low dose (~5-10 IU kg-1 2-3× per week) prophylaxis over episodic treatment in terms of bleed reduction, and quality of life, with improved physical activity, independent functioning, school attendance and community participation. In these nations, the prophylaxis goals should be for improved QoL rather than "zero bleeds" and perfect joints. Prophylaxis can still be individualized to affordability. Higher protective trough level can be achieved by using smaller doses given more frequently without an increase in consumption/cost. The bleeding trigger can also be down-regulated by avoiding unnecessary injury, and by engaging in judicious strengthening exercises appropriate to the joint status to improve balance and joint stabilization. Central to the success of prophylaxis are clinics with comprehensive care that provide the necessary professional expertise, support, and counseling, to educate patients, families, and other healthcare professionals, and to support research for improved hemophilia care.

Demographics and Outcomes of Glenohumeral Dislocations in Individuals With Elevated Body Mass Index.

INTRODUCTION: No specific study has investigated the characteristics and outcomes of anterior shoulder dislocations in morbidly obese individuals. The purpose of this study was to describe shoulder dislocations in patients with body mass index (BMI) greater than 40. METHODS: A retrospective review was conducted to identify patients aged 18 years and older with a BMI ≥40 who presented with a shoulder dislocation in a single institution from 2000 to 2020. Dislocation patterns, associated injuries, treatment modalities, and associated complications were recorded. RESULTS: A significant increase was noted in the number of patients with BMI greater than 40 presenting per year (r2 = -0.831, P < 0.01) over the past 20 years. A significant increase was noted in the average BMI per year in this population (r2 = 0.504, P = 0.028). Fifteen patients (19.5%) experienced at least one recurrent dislocation episode. Ten patients had a Bankart lesion that was associated with an elevated BMI (P = 0.04). Nine patients (11.7%) sustained an associated neurologic injury (no association with BMI). CONCLUSIONS: Over time, there has been an increase in shoulder dislocations in morbidly obese individuals in the United States, alongside an overall increase in the average BMI of patients who present with shoulder dislocations.

Orienteering combines vigorous-intensity exercise with navigation to improve human cognition and increase brain-derived neurotrophic factor.

Exercise enhances aspects of human cognition, but its intensity may matter. Recent animal research suggests that vigorous exercise, which releases greater amounts of lactate, activates more brain-derived neurotrophic factor (BDNF) in the hippocampus and, thus, may be optimal for supporting cognitive function. The cognitive benefits of exercise may be further augmented when combined with cognitive training. The sport of orienteering simultaneously combines exercise with spatial navigation and, therefore, may result in greater cognitive benefits than exercising only, especially at vigorous intensities. The present study aimed to examine the effects of an acute bout of orienteering at different intensities on cognition and BDNF compared to exercising only. We hypothesized that vigorous-intensity orienteering would increase lactate and BDNF and improve cognition more than moderate-intensity orienteering or vigorous exercise alone. Sixty-three recreationally active, healthy young adults (Mage = 21.10±2.75 years) with no orienteering experience completed a 1.3 km intervention course by navigating and exercising at a vigorous (80-85% of heart rate reserve) or moderate (40-50% of heart rate reserve) intensity or exercising vigorously without navigation. Exercise intensity was monitored using peak lactate, heart rate and rating of perceived exertion. Serum BDNF was extracted immediately before and after the intervention. Memory was assessed using the Mnemonic Similarity Task (high-interference memory) and the Groton Maze Learning Test (spatial memory). Both exercising and orienteering at a vigorous intensity elicited greater peak lactate and increases in BDNF than moderate-intensity orienteering, and individuals with higher peak lactate also had greater increases in BDNF. High-interference memory improved after both vigorous-intensity interventions but did not improve after the moderate-intensity intervention. Spatial memory only increased after vigorous-intensity orienteering, suggesting that orienteering at a vigorous intensity may particularly benefit spatial cognition. Overall, the results demonstrate the benefits of vigorous exercise on human cognition and BDNF.

Preeclampsia: Platelet procoagulant membrane dynamics and critical biomarkers.

A state-of-the-art lecture titled "Preeclampsia and Platelet Procoagulant Membrane Dynamics" was presented at the International Society on Thrombosis and Haemostasis (ISTH) Congress in 2022. Platelet activation is involved in the pathophysiology of preeclampsia and contributes to the prothrombotic state of the disorder. Still, it remains unclear what mechanisms initiate and sustain platelet activation in preeclampsia and how platelets drive the thrombo-hemorrhagic abnormalities in preeclampsia. Here, we highlight our findings that platelets in preeclampsia are preactivated possibly by plasma procoagulant agonist(s) and overexpress facilitative glucose transporter-3 (GLUT3) in addition to GLUT1. Preeclampsia platelets are also partially degranulated, procoagulant, and proaggregatory and can circulate as microaggregates/microthrombi. However, in response to exposed subendothelial collagen, such as in injured vessels during cesarean sections, preeclampsia platelets are unable to mount a full procoagulant response, contributing to blood loss perioperatively. The overexpression of GLUT3 or GLUT1 may be monitored alone or in combination (GLUT1/GLUT3 ratio) as a biomarker for preeclampsia onset, phenotype, and progression. Studies to further understand the mediators of the platelet activation and procoagulant membrane dynamics in preeclampsia can reveal novel drug targets and suitable alternatives to aspirin for the management of prothrombotic tendencies in preeclampsia. Finally, we summarize relevant new data on this topic presented during the 2022 ISTH Congress.

Factors associated with mortality after snakebite envenoming in children: a scoping review.

Snakebite envenoming is an important public health issue in many tropical and subtropical countries, where the burden of morbidity and mortality falls particularly on impoverished rural communities. Children are an especially vulnerable group. This scoping review provides an overview of the extent, type and content of peer-reviewed evidence regarding factors associated with mortality in snakebite-envenomed children. A comprehensive literature search of MEDLINE and the Global Index Medicus yielded 623 articles, of which 15 met the criteria for inclusion; 67% of studies were conducted in India, with the remaining studies taking place in Papua New Guinea, Morocco and The Gambia. There was a notable scarcity of eligible studies from sub-Saharan Africa and Latin America despite the high burden of envenoming in these regions. The risk factors for mortality that were identified by the greatest number of studies were younger patient age (n=4), delay in administration of antivenom (n=4) and acute kidney injury (n=3). Identification of poor prognostic factors can assist clinicians in making timely referrals to centres with paediatric critical care capability. Future research must address the lack of studies from key geographical regions so that evidence-based improvements to the care of this vulnerable group can be implemented.

Short-term outcome of unicortical, intramedullary repair of distal biceps ruptures - A retrospective cohort study.

Background: Modern distal biceps reconstruction techniques generally have satisfactory outcomes, but are not without complications. Posterior interosseous nerve (PIN) palsy is a rare but potentially devastating complication of bicortical metal button fixation. Recently, a unicortical, intramedullary, repair technique utilizing a suture anchor has been described. The primary aim of this study was to compare short-term functional and patient-reported outcomes and complication rates in patients receiving unicortical intramedullary repair (UR) with suture anchor against those receiving bicortical repair (BR) with metallic button. We hypothesized that UR would have equally satisfactory outcomes without the complication profile. Methods: Retrospective chart review was conducted for all patients undergoing operative fixation of distal biceps tendon ruptures from 2015 to 2021 at our tertiary referral center. Twenty patients received BR, and eight patients received UR. Patient demographics and surgical complications were compared. QuickDASH scores at two-month and latest in-person and telehealth postoperative visits, as well as elbow and forearm range of motion at last clinical visit, were collected and analyzed. Results: Average patient age in the BR & UR cohorts were 49.3 ± 9.3 and 42.1 ± 6.2 years, respectively, with a male predominance. There was no statistical difference in patient age, sex, hand dominance, injury laterality, injury chronicity, and follow-up duration. Range of motion was comparable and excellent in both groups. Latest follow-up was 3.0 ± 0.5 years in the BR and 1.5 ± 0.4 years in the UR cohorts. QuickDASH scores improved between the two-month and latest time points in each cohort however did not differ significantly in head-to-head comparison. Complications included a case of PIN palsy, distal biceps tendon rerupture, and lateral antebrachial cutaneous nerve (LABC) neuropraxia in the BR group and two cases of LABC neuropraxia in the UR group. The number needed to treat (NNT) for the prevention of one additional case of PIN palsy using UR is 22 patients. Discussion: Short-term functional and patient-reported outcomes in traditional BR and newly reported UR of distal biceps tendon ruptures are comparable and excellent. UR did not have higher failure rate despite follow-up periods beyond what is typically reported for tendon reruptures. In this limited retrospective cohort study, UR also did not encounter postoperative PIN palsy and had an NNT of 22 patients. In the appropriate clinical setting, this provides early evidence supporting the utilization of unicortical intramedullary suture anchor fixation of distal biceps tendon ruptures as well as associated perioperative interventions such as preoperative nerve blocks.