Citations

Abstract Background The Mitral Regurgitation International Database (MIDA) score is a validated tool for Degenerative Mitral Regurgitation (DMR) management, being able to position a given patient within a continuous spectrum of short and long term mortality. However, whether this score may be applicable and incremental in the entire span of Floppy Mitral Valves (FMV), regardless of DMR severity, remains unsubstantiated. Methods The MIDA-Quantitative (MIDA-Q) unprecedented registries include 8187 consecutive patients (age 64±17 years, 45% women, follow-up 5.5±3.4 years) with isolated degenerative mitral valve disease diagnosed at tertiary (European/ North-American/ Middle Eastern) centers in whom DMR severity used both integrative and quantitative grading. The MIDA-Q Score ranged from 0 to 15 depending on accumulating risk factors. Long-term survival overall, under medical management and post-mitral surgery was analysed. Results By quantitative grading, MR was no/trivial in 1938 (24%), mild in 1423 (17%), moderate in 2027 (25%) and severe in 2799 (34%), with ERO 0.24±24cm2, RVol 37±35mL, and posterior leaflet prolapse in 49%. MIDA-Q Scores stratified in 8 categories were 0 (score 0, n=851), 1 (score 1–2, n=1301), 2 (score 3–4, n=2043), 3 (score 5–6, n=1581), 4 (score 7–8, n=1273), 5 (score 9–10, n=718), 6 (score 11–12, n=331) and 7 (score 13–15, n=89). In the whole MIDA-Q population (n=8187 patients), 5-year survival under medical management with Scores categories 0–1, 2–4, and 5–7 was 96±1%, 73±1%, and 61±3% respectively (P<0.0001). Five-year mortality ranged from 3% with MIDA Q-score 0 to 95% with MIDA Q-score 13–15 (P<0.0001). After mitral surgery, 1-year mortality with Scores categories 0–1, 2–4, and 5–7 was 0%, 1%, and 6% respectively and 5-year post-operative survival was 99±1%, 94±1%, and 82±2% (all P<0.0001). In models including age, sex and all guideline-provided prognostic markers, the EuroScoreII and the MIDA Score without DMR severity, the MIDA-Q Score provided incremental prognostic information (P<0.001). Conclusion This unheard international cohort of patients with FMV and prospective mitral severity quantitative grading, enables for the first time the calculation of a MIDA-Q Score, highly determinant of survival after diagnosis of FMV with any degree of DMR, that may be very useful for mitral valve prolapse management. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): Mayo Fundation Figure 1

Abstract Background: COVID-19 caused the worst international public health crisis, accompanied by major global economic downturns, mass-scale job losses, which impacted on the psychosocial wellbeing of the worldwide population. This study examined factors associated with psychosocial distress, fear of COVID-19 and coping strategies amongst the general population in Saudi Arabia.Methods: A cross-sectional study was conducted using an anonymous online questionnaire. Multivariate logistic regressions were used; Adjusted Odds Ratio (AOR) with 95% Confidence Intervals (CIs) was reported.Results: Among 803 participants, 70 %(n=556), were females and the median age was 27 years; 35% (n=278), were frontline or essential service workers; 24% (n=195), reported comorbid conditions including mental health illness. Factors associated with moderate to high levels of psychological distress were: youth (18 - 29 years) (AOR 3.35, 95% CIs 2.06 - 5.44), females (2.59, 1.60 - 4.19), non-Saudi nationals (2.17, 1.11 - 4.26), change in employment (2.9, 1.73 - 4.87), negative financial impact (2.14, 1.29-3.56), having comorbidities (2.67, 1.47 - 4.87), and current smoking (2.87, 1.55 - 5.33). Being ex-smokers (3.72, 1.14 - 12.14) and change in employment (3.42, 1.91 - 6.11) were associated with higher levels of fear of COVID-19. People whose financial situation was impacted and who had contact with known/suspected cases (1.63, 1.12-2.38) had low medium to high resilient coping.Conclusions: People in Saudi Arabia were at a higher risk of psychosocial distress and fear along with low resilience during the COVID-19 pandemic, warranting urgent attention from healthcare providers and policymakers, to provide specific mental health support strategies for their wellbeing currently and to avoid a post-pandemic mental health crisis.

Background Standard therapy for COVID-19 is continuously evolving. Autopsy studies showed high prevalence of platelet-fibrin-rich microthrombi in several organs. The aim of the study was therefore to evaluate the safety and efficacy of antiplatelet therapy (APT) in hospitalised patients with COVID-19 and its impact on survival. Methods 7824 consecutive patients with COVID-19 were enrolled in a multicentre international prospective registry (Health Outcome Predictive Evaluation-COVID-19 Registry). Clinical data and in-hospital complications were recorded. Data on APT, including aspirin and other antiplatelet drugs, were obtained for each patient. Results During hospitalisation, 730 (9%) patients received single APT (93%, n=680) or dual APT (7%, n=50). Patients treated with APT were older (74±12 years vs 63±17 years, p<0.01), more frequently male (68% vs 57%, p<0.01) and had higher prevalence of diabetes (39% vs 16%, p<0.01). Patients treated with APT showed no differences in terms of in-hospital mortality (18% vs 19%, p=0.64), need for invasive ventilation (8.7% vs 8.5%, p=0.88), embolic events (2.9% vs 2.5% p=0.34) and bleeding (2.1% vs 2.4%, p=0.43), but had shorter duration of mechanical ventilation (8±5 days vs 11±7 days, p=0.01); however, when comparing patients with APT versus no APT and no anticoagulation therapy, APT was associated with lower mortality rates (log-rank p<0.01, relative risk 0.79, 95% CI 0.70 to 0.94). On multivariable analysis, in-hospital APT was associated with lower mortality risk (relative risk 0.39, 95% CI 0.32 to 0.48, p<0.01). Conclusions APT during hospitalisation for COVID-19 could be associated with lower mortality risk and shorter duration of mechanical ventilation, without increased risk of bleeding. Trial registration number NCT04334291.

Background Most patients with advanced melanomas relapse after checkpoint blockade therapy. Thus, immunotherapies are needed that can be applied safely early, in the adjuvant setting. Seviprotimut-L is a vaccine containing human melanoma antigens, plus alum. To assess the efficacy of seviprotimut-L, the Melanoma Antigen Vaccine Immunotherapy Study (MAVIS) was initiated as a three-part multicenter, double-blind, placebo-controlled phase III trial. Results from part B1 are reported here. Methods Patients with AJCC V.7 stage IIB-III cutaneous melanoma after resection were randomized 2:1, with stage stratification (IIB/C, IIIA, IIIB/C), to seviprotimut-L 40 mcg or placebo. Recurrence-free survival (RFS) was the primary endpoint. For an hypothesized HR of 0.625, one-sided alpha of 0.10, and power 80%, target enrollment was 325 patients. Results For randomized patients (n=347), arms were well-balanced, and treatment-emergent adverse events were similar for seviprotimut-L and placebo. For the primary intent-to-treat endpoint of RFS, the estimated HR was 0.881 (95% CI: 0.629 to 1.233), with stratified logrank p=0.46. However, estimated HRs were not uniform over the stage randomized strata, with HRs (95% CIs) for stages IIB/IIC, IIIA, IIIB/IIIC of 0.67 (95% CI: 0.37 to 1.19), 0.72 (95% CI: 0.35 to 1.50), and 1.19 (95% CI: 0.72 to 1.97), respectively. In the stage IIB/IIC stratum, the effect on RFS was greatest for patients <60 years old (HR=0.324 (95% CI: 0.121 to 0.864)) and those with ulcerated primary melanomas (HR=0.493 (95% CI: 0.255 to 0.952)). Conclusions Seviprotimut-L is very well tolerated. Exploratory efficacy model estimation supports further study in stage IIB/IIC patients, especially younger patients and those with ulcerated melanomas. Trial registration number NCT01546571.

Importance Monochorionic (MC) twins are hemodynamically connected by vascular anastomoses within the single shared placenta. The transfer of fluid or blood from one fetus to the other may result in development of pathologic complications, such as twin-twin transfusion syndrome, twin anemia polycythemia sequence, selective intrauterine growth restriction, and twin reversed arterial perfusion sequence. Monoamniotic gestations, which comprise a small fraction of MC pregnancies, can also present with unique challenges, particularly antepartum umbilical cord entanglement. All these complications carry a high risk of fetal morbidity and mortality if not recognized and managed in a timely fashion. Objective The purpose of this article is to review evidence-based management of complicated MC twin gestations and propose a standardized approach to surveillance. Evidence Acquisition Monochorionic gestations account for the majority of complications that occur in twin pregnancies; however, there is unclear evidence on the appropriate surveillance for and management of specific complications associated with these pregnancies. Results This article summarizes management for each specific type of MC complication in a structured and clear manner. Conclusions Early pregnancy ultrasound, ideally between 10 and 13 weeks' gestation, is critical for the diagnosis and characterization of twin pregnancies. To improve outcomes for MC twins, appropriate fetal surveillance should be initiated at 16 weeks' gestation and continued until delivery. Relevance Improve perinatal outcomes in MC twin pregnancies. Target Audience Obstetricians and gynecologists, family physicians Learning Objectives After completing this activity, the learner should be better able to describe the sonographic findings used to establish the diagnosis of MC twin pregnancies; identify complications unique to MC twins pregnancies, including twin-twin transfusion syndrome, twin reversed arterial perfusion sequence, twin anemia polycythemia syndrome, co-twin demise, cord entanglement, and conjoined twins; and explain the management of complications associated with MC twin pregnancies.

Abstract Targeting interactions between α4β7 integrin and endothelial adhesion molecule MAdCAM-1 to inhibit lymphocyte migration to the gastrointestinal tract is an effective therapy in inflammatory bowel disease (IBD). Following lymphocyte entry into the mucosa, a subset of these cells expresses αEβ7 integrin, which is expressed on proinflammatory lymphocytes, to increase cell retention. The factors governing lymphocyte migration into the intestinal mucosa and αE integrin expression in healthy subjects and IBD patients remain incompletely understood. We evaluated changes in factors involved in lymphocyte migration and differentiation within tissues. Both ileal and colonic tissue from active IBD patients showed upregulation of ICAM-1, VCAM-1, and MAdCAM-1 at the gene and protein levels compared with healthy subjects and/or inactive IBD patients. β1 and β7 integrin expression on circulating lymphocytes was similar across groups. TGF-β1 treatment induced expression of αE on both β7+ and β7− T cells, suggesting that cells entering the mucosa independently of MAdCAM-1/α4β7 can become αEβ7+. ITGAE gene polymorphisms did not alter protein induction following TGF-β1 stimulation. Increased phospho-SMAD3, which is directly downstream of TGF-β, and increased TGF-β–responsive gene expression were observed in the colonic mucosa of IBD patients. Finally, in vitro stimulation experiments showed that baseline β7 expression had little effect on cytokine, chemokine, transcription factor, and effector molecule gene expression in αE+ and αE− T cells. These findings suggest cell migration to the gut mucosa may be altered in IBD and α4β7−, and α4β7+ T cells may upregulate αEβ7 in response to TGF-β once within the gut mucosa.