The importance of collaboration in maternal medicine: A retrospective descriptive study of a maternal multidisciplinary team meeting.

OBJECTIVE: In the present study we aimed to review the evolution and function of the maternal medicine multidisciplinary team (MMMDT) meeting of a maternal medicine service of a tertiary level stand-alone maternity hospital. METHODS: We conducted a retrospective descriptive study of all minutes of MMMDT meetings from 2014 to 2020, with the aim of evaluating meeting characteristics and patient demographics. RESULTS: There were 575 multidisciplinary team (MDT) discussions of 486 women during 43 meetings in the 7 year period. On average, 13 (range 3-23; SD = 5.28) women were discussed at each meeting, attended by 17 (range: 11-27; SD = 4.26) attendees. There were 18 women discussed during successive pregnancies. When analyzing the 2017-2020 data, preconceptual discussions made up 7.3% (n = 42) of patients discussed, with 5.7% (n = 33) being postnatal. The mean maternal age was 32.5 years (range 15-48 years) and women were most likely to be discussed in the mid-trimester period (21-24 weeks gestation). The top five primary specialities involved were hematology, neurology, rheumatology, neurosurgery and gastroenterology; however, 22 specialities were represented overall when classified by the primary medical condition. When examining the MDT input, hematology input was required in 144 patients (25.0%), radiology in 161 (28.0%) patients, and 117 in anesthesiology (20.3%). When examining the number of teams required to manage the patient, 80 women required the input of three specialities, with 16 women requiring the input of four specialities. CONCLUSION: We demonstrate the value and role of the MDT in the management of complex patients, providing a forum to discuss care in all phases of the obstetric journey.

VTE Risk Assessment and Prevention in Pregnancy.

Venous thromboembolism (VTE) remains the leading cause of maternal mortality in pregnancy and the postpartum period. In addition to the higher pregnancy-associated baseline VTE risk, there are several well-established risk factors that can further increase the risk of VTE. At present, a thorough interrogation of these risk factors remains our only tool for estimating which pregnant people may be at an increased risk of VTE, and thus potentially benefit from thromboprophylaxis. However, an important knowledge gap still exists surrounding the duration of increased risk and the interaction of risk factors with each other. Furthermore, up to now, once significant risk has been established, prevention strategies have been largely based on expert opinion rather than high-quality data. Recent trials have successfully bridged a proportion of this knowledge gap; however, the challenge of conducting high-quality clinical trials with pregnant people remains. In this article, we provide an update on the recent evidence surrounding VTE risk factors in pregnancy while concurrently outlining knowledge gaps and current approaches to VTE prevention.

The effect of UVA light/8-methoxypsoralen exposure used in Extracorporeal Photopheresis treatment on platelets and extracellular vesicles.

Extracorporeal Photopheresis (ECP) is a leukapheresis based treatment for Cutaneous T-Cell Lymphoma, which takes advantage of the cellular lethal effects of UVA light in combination with a photoactivated drug, 8-methoxypsoralen. 25% of patients treated with ECP do not respond to treatment, however the underlying mechanisms for this lack of response remain unknown. Platelets, a rich source of extracellular vesicles (EVs) and key mediators in thromboinflammatory oncological progression, as well as leukocytes, are both processed through ECP and are subsequently transfused back into the patient, delivering potent immunomodulation. The effect of exposing platelets and their EVs directly to Ultra Violet A light (UVA)/8-methoxypsoralen is currently unknown. Platelet-rich plasma (PRP) was isolated from healthy donors and exposed to UVA light and/or 8-methoxysporalen in vitro and platelet activation and aggregation was assessed. EV size and concentration were also characterised by Nanoparticle Tracking Analysis and Flow Cytometry. We found that UVA light and 8-methoxypsoralen treatment in vitro does not induce platelet aggregation or significantly alter levels of the platelet activation markers, soluble P-selectin or platelet factor 4, with circulating levels of small and large EV size and concentration remaining constant. Therefore, utilising the combination of UVA light and 8-methoxypsoralen used in ECP in vitro does not activate platelets or alter important circulating EVs. Further studies will be needed to validate if our observations are consistent in vivo.

Extracellular vesicles in disorders of hemostasis following traumatic brain injury.

Traumatic brain injury (TBI) is a global health priority. In addition to being the leading cause of trauma related death, TBI can result in long-term disability and loss of health. Disorders of haemostasis are common despite the absence of some of the traditional risk factors for coagulopathy following trauma. Similar to trauma induced coagulopathy, this manifests with a biphasic response consisting of an early hypocoagulable phase and delayed hypercoagulable state. This coagulopathy is clinically significant and associated with increased rates of haemorrhagic expansion, disability and death. The pathophysiology of TBI-induced coagulopathy is complex but there is biologic plausibility and emerging evidence to suggest that extracellular vesicles (EVs) have a role to play. TBI and damage to the blood brain barrier result in release of brain-derived EVs that contain tissue factor and phosphatidylserine on their surface. This provides a platform on which coagulation can occur. Preclinical animal models have shown that an early rapid release of EVs results in overwhelming activation of coagulation resulting in a consumptive coagulopathy. This phenomenon can be attenuated with administration of substances to promote EV clearance and block their effects. Small clinical studies have demonstrated elevated levels of procoagulant EVs in patients with TBI correlating with clinical outcome. EVs represent a promising opportunity for use as minimally invasive biomarkers and potential therapeutic targets for TBI patients. However, additional research is necessary to bridge the gap between their potential and practical application in clinical settings.

Retrospective cross-sectional analysis of concurrent VTE diagnosis in hospitalised socially excluded individuals in Ireland.

OBJECTIVE: Social exclusion (such as that experienced by people who are homeless, incarcerated or use drugs) increases morbidity across a range of diseases but is poorly captured in routine data sets. The aim of this study was to use a novel composite variable in a national-level hospital usage dataset to identify social exclusion and to determine whether social exclusion is associated with concurrent venous thromboembolism (VTE) in hospitalised patients in Ireland. Identifying and characterising this association in people who are socially excluded will inform VTE prevention and treatment strategies. DESIGN: Retrospective cross-sectional study. SETTING: Irish Hospital Inpatient Enquiry (HIPE) system, which collects diagnostic information by International Classification of Diseases Tenth Revision code on all hospital admission episodes in the Ireland. PARTICIPANTS: All hospital admission episodes involving a VTE diagnosis (in a primary 'Dx 1' or secondary 'Dx 2-30' coding position) during a 12-month period in the Ireland were identified from consolidated, national-level datasets derived from the Irish HIPE system. Social exclusion was defined as the presence of one or more indicators of homelessness, drug use, incarceration, health hazards due to socioeconomic status or episodes of healthcare terminated prematurely. RESULTS: Of 5701 admission episodes involving a VTE diagnosis (in a primary or secondary position) during the study period, 271 (4.8%) related to an individual affected by social exclusion. Among hospitalised individuals identified as being socially excluded based on the novel composite variable, the likelihood of having a concurrent VTE diagnosis was over twofold greater than that observed in the general population (OR 2.14, 95% CI 1.79 to 2.26; p<0.001). CONCLUSION: These data suggest that VTE (primary and secondary) is over-represented in hospitalised socially excluded persons in Ireland and that the development of strategies to address this potentially life-threatening accompanying condition in this vulnerable patient group must be prioritised.

Proteomic analysis of extracellular vesicle cargoes mirror the cardioprotective effects of rivaroxaban in patients with venous thromboembolism.

BACKGROUND: Venous thromboembolism (VTE) remains a significant cause of morbidity and mortality worldwide. Rivaroxaban, a direct oral factor Xa inhibitor, mediates anti-inflammatory and cardiovascular-protective effects besides its well-established anticoagulant properties; yet, these remain poorly characterized. Extracellular vesicles (EVs) are considered proinflammatory messengers regulating a myriad of (patho)physiological processes and may be highly relevant to the pathophysiology of VTE. The effects of Rivaroxaban on circulating EVs in VTE patients remain unknown. We have established that differential EV biosignatures are found in patients with non-valvular atrial fibrillation anticoagulated with Rivaroxaban versus warfarin. Here, we investigated whether differential proteomic profiles of circulating EVs could also be found in patients with VTE. METHODS AND RESULTS: We performed comparative label-free quantitative proteomic profiling of enriched plasma EVs from VTE patients anticoagulated with either Rivaroxaban or warfarin using a tandem mass spectrometry approach. Of the 182 quantified proteins, six were found to be either exclusive to, or enriched in, Rivaroxaban-treated patients. Intriguingly, these proteins are involved in negative feedback regulation of inflammatory and coagulation pathways, suggesting that EV proteomic signatures may reflect both Rivaroxaban's anti-coagulatory and anti-inflammatory potential. CONCLUSIONS: These differences suggest Rivaroxaban may have pleiotropic effects, supporting the reports of its emerging anti-inflammatory and cardiovascular-protective characteristics relative to warfarin.

Unmet needs and barriers in venous thromboembolism education and awareness among people living with cancer: a global survey.

BACKGROUND: Venous thromboembolism (VTE) is a major preventable cause of morbidity, disability, and mortality in subjects with cancer. A global appraisal of cancer-associated VTE education and awareness is not available. OBJECTIVES: To evaluate VTE-related education, awareness, and unmet needs from the perspective of people living with cancer using a quantitative and qualitative approach. METHODS: This cross-sectional study used data from an online-based survey covering multidimensional domains of cancer-associated VTE. Data are presented descriptively. Potential differences across participant subgroups were explored. RESULTS: Among 2262 patients with cancer from 42 countries worldwide, 55.3% received no VTE education throughout their cancer journey, and an additional 8.2% received education at the time of VTE diagnosis only, leading to 63.5% receiving no or inappropriately delayed education. When education was delivered, only 67.8% received instructions to seek medical attention in case of VTE suspicion, and 36.9% reported scarce understanding. One-third of participants (32.4%) felt psychologically distressed when becoming aware of the potential risks and implications connected with cancer-associated VTE. Most responders (78.8%) deemed VTE awareness highly relevant, but almost half expressed concerns about the quality of education received. While overall consistent, findings in selected survey domains appeared to numerically differ across age group, ethnicity, continent of residence, educational level, metastatic status, and VTE history. CONCLUSION: This study involving a large and diverse population of individuals living with cancer identifies important unmet needs in VTE-related education, awareness, and support across healthcare systems globally. These findings unveil multilevel opportunities to expedite patient-centered care in cancer-associated VTE prevention and management.