Early Bleeding Research Articles

Bleeding and Subsequent Cardiovascular Events and Death in Atrial Fibrillation With Stable Coronary Artery Disease: Insights From the AFIRE Trial.

Early bleeding after percutaneous coronary intervention is associated with increased risk of death and myocardial infarction; however, the association between bleeding and subsequent major adverse cardiac and cerebrovascular events (MACCE) remains unclear in patients with atrial fibrillation and stable coronary artery disease. We thus aimed to investigate this association. The AFIRE trial (Atrial Fibrillation and Ischemic Events With Rivaroxaban in Patients With Stable Coronary Artery Disease) was a multicenter, open-label trial conducted in Japan. This post hoc analysis included 2215 patients with atrial fibrillation and stable coronary artery disease treated with rivaroxaban or rivaroxaban plus an antiplatelet agent. MACCE was defined as a composite of stroke, systemic embolism, myocardial infarction, unstable angina requiring revascularization, or death from any cause. The association of bleeding with subsequent MACCE risk was investigated using time-adjusted Cox multivariate analysis after adjusting for baseline characteristics and time from bleeding. Bleeding events were classified according to the International Society on Thrombosis and Haemostasis criteria. Among the 2215 patients, 386 (17.4%) had bleeding during follow-up, of whom 63 (16.3%) also experienced MACCE; MACCE incidence was higher in patients with bleeding than in those without (8.38% versus 4.20% per patient-year; hazard ratio, 2.01 [95% CI, 1.49-2.70]; P<0.001). The proportion of patients with both bleeding and MACCE (developed after bleeding) was 73.0% (46 of 63); 27.0% (17 of 63) experienced MACCE before bleeding. Time-adjusted Cox multivariate analysis revealed a temporal association between major bleeding and subsequent MACCE, with particularly high MACCE risks within 30 days after major bleeding (hazard ratio, 7.81 [95% CI, 4.20-14.54]). In patients with atrial fibrillation and stable coronary artery disease, major bleeding was strongly associated with subsequent MACCE. Thus, it is important to prevent major bleeding to avoid cardiovascular events and death. Registration: URL: https://www.umin.ac.jp/ctr; Unique identifier: UMIN000016612. URL: https://www.clinicaltrials.gov; Unique identifier: NCT02642419. Graphic Abstract: A graphic abstract is available for this article.

Effect of implementing bundle care on reducing early Postpartum haemorrhage among primiparous

Background: Postpartum hemorrhage (PPH) is associated with an increased risk of complications after delivery for both the mother and the newborn in postnatal period and later life. Aim: Aim of the study was to assess the effect of implementing bundle care on reducing early postpartum haemorrhage among primiparous.Methods: A quasi-experimental design (nonequivalent control group pretest/posttest) was adopted. Setting: The current study was conducted in the postpartum words of Obstetrics and Gynecology department in Maternity hospital, Portsaid Governorate, Egypt. A purposive sample of 70 primiparous with early PPH was carefully chosen from the nominated setting and dispersed accidentally into two equal groups (study and control group). Two tools were used for collecting the study data: A structured interviewing questionnaire schedule and tool of bundle care of early PPH that consists of three parts.Results: There is a statistically significant difference between the study and control groups in reducing early PPH among primiparous and improve outcomes. The current study results display that the primiparous outcomes improved in study group compared to control group which seemed in mild of bleeding 68.6% in study group, 37.1in control group and conscious level 94.3% in study group, 60% in control group with normal conscious level. The study group have lower complications, compared to complications of the control group. Conclusion: Bundle care was effective in decreasing blood loss complications of early PPH. Recommendations: Bundle care should be recommended as a nursing intervention protocol and should become a fundamental part of the total management of early PPH.

Effect of Guideline on Improving Nurses' Practices for Patients with Early Postpartum Haemorrhage

Background: postpartum hemorrhage (PPH) is still one of the main causes responsible for maternal morbidity and mortality. Aim of the study: To investigate the effect of guideline on improving nurses' practices for patients with early postpartum hemorrhage. Setting: At obstetric departments in Damanhur teaching hospital at Beheira Governorate. Study Design: A Quasi- experimental (an interventional pre and posttest study). Subject type: purposive sample. Subject size: All nurses (44nurses) who were working at obstetric departments and accepted to participate in study, at previously mentioned study setting. Four nurses were excluded from the total sample due to their participation in the pilot study. Tools: Three tools 1) a structured interviewing questionnaire. 2) An observational checklist. And 3) Nurses' satisfaction tool. Results: The result of the present study findings was highly significant improvement in total knowledge and total practical skills among the studied sample pre intervention compared to immediate and eight weeks post intervention. P= < 0.01. Additionally, about more than three quarter among studied sample satisfied with the advanced knowledge included in guideline. Conclusion: the present study findings concluded that a significant improvement among studied sample' knowledge and practices post intervention. Recommendations: Nursing standards, protocols and guideline must be designed to enhance nurses' knowledge, practices and satisfaction

Ascorbic Acid to Prevent Postpolypectomy Bleeding in the Colon: A Randomized Controlled Trial.

It has been reported that vitamin C replacement can quickly reverse nonspecific bleeding in surgical patients with normal coagulation parameters. We evaluated the effect of intravenous ascorbic acid administration for prevention of postpolypectomy bleeding in large polyps of the colon. Patients with large polyps with heads larger than 10 mm, stalk diameter larger than 5 mm, and a length larger than 10 mm were included in this randomized controlled clinical trial. In the study group, the first 500 mg intravenous dose of vitamin C diluted in normal saline was administered 2h before colonoscopic resection of polyps and the second and third similar doses were administered on days 2 and 3 of polypectomy, respectively. The control group received normal saline in a similar fashion. The resection of polyps was performed in snare and cut-blend mode. Early and late postoperative bleeding were compared between the two groups. A total of 153 polyps were resected by endoscopic polypectomy. Early bleeding was observed in 7.2% of the patients, which was significantly lower in the vitamin C group (2.6% vs 11.8%, P =0.03). Late bleeding was observed in 6.5% of the patients with a trend lower in the vitamin C group (2.6% vs 10.5%, P =0.057). The proportion of postprocedural bleeding was significantly higher in the vitamin C group (5% vs 20%, P =0.007). Hazard ratios of early and postprocedural bleeding were 78% and 76% lower in the vitamin C group compared to the control group (P <0.05). Intravenous ascorbic acid infusion could reduce postpolypectomy bleeding.

Endoscopic submucosal dissection vs. endoscopic mucosal resection for early Barrett's neoplasia in the West: a retrospective study.

The difference in clinical outcomes after endoscopic submucosal dissection (ESD) and endoscopic mucosal resection (EMR) for early Barrett's esophagus (BE) neoplasia remains unclear. We compared the recurrence/residual tissue rates, resection outcomes, and adverse events after ESD and EMR for early BE neoplasia. We included patients who underwent EMR or ESD for BE-associated high grade dysplasia (HGD) or T1a esophageal adenocarcinoma (EAC) at eight academic hospitals. We compared demographic, procedural, and histologic characteristics, and follow-up data. A time-to-event analysis was performed to evaluate recurrence/residual disease and a Kaplan-Meier curve was used to compare the groups. 243 patients (150 EMR; 93 ESD) were included. EMR had lower en bloc (43 % vs. 89 %; P < 0.001) and R0 (56 % vs. 73 %; P = 0.01) rates than ESD. There was no difference in the rates of perforation (0.7 % vs. 0; P > 0.99), early bleeding (0.7 % vs. 1 %; P > 0.99), delayed bleeding (3.3 % vs. 2.1 %; P = 0.71), and stricture (10 % vs. 16 %; P = 0.16) between EMR and ESD. Patients with non-curative resections who underwent further therapy were excluded from the recurrence analysis. Recurrent/residual disease was 31.4 % [44/140] for EMR and 3.5 % [3/85] for ESD during a median (interquartile range) follow-up of 15.5 (6.75-30) and 8 (2-18) months, respectively. Recurrence-/residual disease-free survival was significantly higher in the ESD group. More patients required additional endoscopic resection procedures to treat recurrent/residual disease after EMR (EMR 24.2 % vs. ESD 3.5 %; P < 0.001). ESD is safe and results in more definitive treatment of early BE neoplasia, with significantly lower recurrence/residual disease rates and less need for repeat endoscopic treatments than with EMR.

Current aspects of the progress of labor in healthy women according to the data of the retrospective analysis

Purpose of the work – to study the current aspects of the course of labor in healthy women using retrospective indicators.Material and methods. To study this topic, an analysis of 1.078 births of women who were born on the basis of the maternity ward for pregnant women with obstetric pathology of the State Institution «Institute of Pediatrics,Obstetrics and Gynecology named after acad. O.M. Lukyanova National Academy of Medical Sciences of Ukraine». It was found that of all births, the proportion of first-borns was 602 (55.8 %) women, of whom 451 (41.8 %) were pregnant, and only 86 (8 %) were healthy pregnant women, which we will study in the future.Results. It was found that among 86 births, the frequency of physiological births was 64 %, of which in 47.7 % of cases childbirth was complicated, and pathological – 36 %. The most common complications during childbirth were: premature rupture of membranes (PRPO), episio- and perineotomy, trauma to the birth canal. The causes of pathological childbirth in the examined women were: abnormalities of labor, fetal distress, defect of manure and membranes, clinically narrow pelvis, malposition of the fetus and early postpartum hemorrhage. All children were born alive. It should be noted that all births, where the Apgar score was ≤ 6 points, had no partner support, and the women themselves did not undergo any preparation for childbirth. Conclusions. According to our data, in almost healthy women who gave birth for the first time and had no perinatal loss in the anamnesis, did not undergo prenatal training and did not have partner support during childbirth, the number of complications during childbirth is increasing. Therefore, this group of healthy pregnant women needs more detailed study and analysis, development of prenatal training algorithms to improve perinatal indicators.

Thromboembolic complications among multiple injured patients with pelvic injuries: identifying risk factors for possible patient-tailored prophylaxis

BackgroundPatients with pelvic and/or acetabular fractures are at high risk of developing thromboembolic (TE) complications. In our study we investigate TE complications and the potential negative effects of concomitant pelvic or acetabular injuries in multiple injured patients according to pelvic/acetabular injury severity and fracture classification.MethodsThe TraumaRegister DGU® was analyzed between 2010 and 2019. Multiple injured patients with pelvic and/or acetabular fractures with ISS ≥ 16 suffering from TE complications were identified. We conducted a univariate and multivariate analysis with TE events as independent variable to examine potential risk factors and contributing factors.Results10.634 patients met our inclusion criteria. The overall TE incidence was 4.9%. Independent risk factors for the development of TE complications were sepsis, ≥ 10 operative interventions, mass transfusion (≥ 10 PRBCs), age ≥ 65 years and AISAbdomen ≥ 3 (all p < 0.001). No correlation was found for overall injury severity (ISS), moderate traumatic brain injury, additional injury to lower extremities, type B and C pelvic fracture according to Tile/AO/OTA and closed or open acetabular fracture.ConclusionsMultiple injured patients suffering from pelvic and/or acetabular fractures are at high risk of developing thromboembolic complications. Independent risk factors for the development of thromboembolic events in our study cohort were age ≥ 65 years, mass transfusion, AISAbdomen ≥ 3, sepsis and ≥ 10 surgery procedures. Among multiple injured patients with acetabular or pelvic injuries the severity of these injuries seems to have no further impact on thromboembolic risk. Our study, however, highlights the major impact of early hemorrhage and septic complications on thromboembolic risk in severely injured trauma patients. This may lead to individualized screening examinations and a patient-tailored thromboprophylaxis in high-risk patients for TE. Furthermore, the number of surgical interventions should be minimized in these patients to reduce thromboembolic risk.

Anti-Vascular Endothelial Growth Factor Therapy as an Adjunct to Diabetic Vitrectomy

Introduction: The purpose of this work is to study the efficacy of the preoperative intravitreal administration of bevacizumab as an adjunct to vitrectomy in patients with Proliferative Diabetic Retinopathy (PDR). Methods: This retrospective comparative study was performed on 118 eyes (118 patients) with proliferative diabetic retinopathy (PDR), which underwent vitrectomy surgery at the Department of Diabetic Eye Disease at Zarifa Aliyeva National Ophthalmology Centre (Baku, Azerbaijan) in 2015-2019. The main group (the bevacizumab group) included 48 eyes with PDR that received intravitreal administration of bevacizumab (Avastin; Genentech Inc., USA) within one week before vitrectomy; the control group included 70 eyes that did not receive a bevacizumab injection for at least 3 months before the vitrectomy. The minimum follow-up was 12 months. Results: In both groups, complete retinal attachment after primary vitrectomy was achieved in all eyes (100%). Clinically significant intraoperative haemorrhage was observed in the preoperative bevacizumab injection group in 31.2% and the control group- 51.4%, p = 0.030. The preoperative bevacizumab injection reduced the risk of clinically significant haemorrhage by 2.3 times and the need for endodiathermy by 2.7 times (p = 0.031 and p = 0.024, respectively). Early vitreous cavity haemorrhage was observed in 15.0% in the bevacizumab group and in 35.5% in the control group (p = 0.038). The preoperative injection of bevacizumab before vitrectomy reduced the risk of vitreous cavity haemorrhage in the early postoperative period by 3.0 times (p = 0.036). Conclusion: The preoperative use of bevacizumab as an adjunct to diabetic vitrectomy can help reduce the incidence of intraoperative and early postoperative vitreous cavity haemorrhage, which leads to better functional results in the early postoperative period. Over the long-term follow-up period, the effect of the preoperative bevacizumab injections decreases.

Pharmacokinetics of Intravenous Paracetamol (Acetaminophen) and Ductus Arteriosus Closure After Premature Birth.

In preterm infants, a high risk of hemodynamically significant patent ductus arteriosus (PDA) exists and its persistence is associated with an increased risk of severe morbidity. Current pharmacological options include ibuprofen or indomethacin. However, treatment by indomethacin or ibuprofen of a large PDA was shown to reduce early pulmonary hemorrhage and later medical treatment but had no effect on neonatal death or morbidity. Early prophylactic treatment of ductus arteriosus by paracetamol seems to be an attractive opportunity to reduce life-threatening morbidity. However, there are currently no data regarding the pharmacokinetics (PK) and pharmacodynamics of paracetamol in preterm neonates in this potential new indication. In this study, we aimed to develop a population PK model for paracetamol and investigate the relationship between paracetamol exposure levels and time to contraction of the ductus. Data were modeled using Monolix software. A one-compartment model adequately described the paracetamol concentration-time course. A Weibull model adequately described the time to contraction of the ductus. Our results suggest that the dosage used in this study (i.e., first day 42.5mg/kg, then 30mg/kg/day) allows for reaching the maximum inhibition response from paracetamol regarding the time to close the ductus. However, this study pointed out a lower effect of paracetamol on extremely preterm neonates (below 27weeks). Therefore, a dose-finding study focusing specifically on extremely preterm neonates with treatment efficacy and toxicity is strongly needed.

Available Bleeding Scoring Systems Poorly Predict Major Bleeding in the Acute Phase of Pulmonary Embolism.

We aimed to compare six available bleeding scores, in a real-life cohort, for prediction of major bleeding in the early phase of pulmonary embolism (PE). We recorded in-hospital characteristics of 2754 PE patients in a prospective observational multicenter cohort contributing 18,028 person-days follow-up. The VTE-BLEED (Venous Thrombo-Embolism Bleed), RIETE (Registro informatizado de la enfermedad tromboembólica en España; Computerized Registry of Patients with Venous Thromboembolism), ORBIT (Outcomes Registry for Better Informed Treatment), HEMORR2HAGES (Hepatic or Renal Disease, Ethanol Abuse, Malignancy, Older Age, Reduced Platelet Count or Function, Re-Bleeding, Hypertension, Anemia, Genetic Factors, Excessive Fall Risk and Stroke), ATRIA (Anticoagulation and Risk Factors in Atrial Fibrillation), and HAS-BLED (Hypertension, Abnormal Renal/Liver Function, Stroke, Bleeding History or Predisposition, Labile International Normalized Ratio, Elderly, Drugs/Alcohol) scores were assessed at baseline. International Society on Thrombosis and Haemostasis (ISTH)-defined bleeding events were independently adjudicated. Accuracy of the overall original 3-level and newly defined optimal 2-level outcome of the scores were evaluated and compared. We observed 82 first early major bleedings (3.0% (95% CI, 2.4–3.7)). The predictive power of bleeding scores was poor (Harrel’s C-index from 0.57 to 0.69). The RIETE score had numerically higher model fit and discrimination capacity but without reaching statistical significance versus the ORBIT, HEMORR2HAGES, and ATRIA scores. The VTE-BLEED and HAS-BLED scores had significantly lower C-index, integrated discrimination improvement, and net reclassification improvement compared to the others. The rate of observed early major bleeding in score-defined low-risk patients was high, between 15% and 34%. Current available scoring systems have insufficient accuracy to predict early major bleeding in patients with acute PE. The development of acute-PE-specific risk scores is needed to optimally target bleeding prevention strategies.

Protein fucosylation is required for Notch dependent vascular integrity in zebrafish

The onset of circulation in a developing embryo requires intact blood vessels to prevent hemorrhage. The development of endothelial cells, and their subsequent recruitment of perivascular mural cells are important processes to establish and maintain vascular integrity. These processes are genetically controlled during development, and mutations that affect endothelial cell specification, pattern formation, or maturation through the addition of mural cells can result in early developmental hemorrhage. We created a strong loss of function allele of the zebrafish GDP-mannose 4,6 dehydratase (gmds) gene that is required for the de novo synthesis of GDP-fucose, and homozygous embryos display cerebral hemorrhages. Our data demonstrate that gmds mutants have early defects in vascular patterning with ectopic branches observed at time of hemorrhage. Subsequently, defects in the number of mural cells that line the vasculature are observed. Moreover, activation of Notch signaling rescued hemorrhage phenotypes in gmds mutants, highlighting a potential downstream pathway that requires protein fucosylation for vascular integrity. Finally, supplementation with fucose can rescue hemorrhage frequency in gmds mutants, demonstrating that synthesis of GDP-fucose via an alternative (salvage) pathway may provide an avenue toward therapeutic correction of phenotypes observed due to defects in de novo GDP-fucose synthesis. Together, these data are consistent with a novel role for the de novo and salvage protein fucosylation pathways in regulating vascular integrity through a Notch dependent mechanism.

O-225 Effects of SARS-Corona virus 2 on IVF treatment parameters: A cohort study of post COVID-19 patients

Abstract Study question Does recovery from SARS–Corona virus 2 (SARS–CoV-2) infection negatively effect IVF cycle parameters? Summary answer Female IVF treatment parameters were comparable to the pre-Covid-19 infection cycle performance. Sperm concentration and motility demonstrated lower mean counts following Covid-19 infection. What is known already Corona-virus disease-19 (Covid-19) is a global pandemic caused by SARS–Corona virus 2 (SARS–CoV-2). The virus primarily affects the respiratory system, but other systemic and immune mediated effects have been reported. The spikes of SARS-CoV-2 have strong affinity for the Angiotensin converting enzyme (ACE) 2 receptor, leading to an increased Angiotensin II (Ang II) mediated pro-inflammatory response. ACE2 receptors exist in the human reproductive tract (more in males) and pose a regulatory role together with Ang II. So far, reports have been inconsistent regarding testicular effects. Other implications involving fertility and fertility treatment post infection are scarce. Study design, size, duration In this retrospective cohort study, IVF cycle performance was compared before and after Corona-virus disease-19. Patients were included only in cases where an IVF cycle was initiated within 3 months of Covid-19 recovery, between March 2020-December 2020. Participants/materials, setting, methods The study was conducted in a University affiliated IVF unit. Post Covid- 19 cycle parameters were compared to previous cycles of the same individual prior to infection. If previous cycles were not available, parameters were compared to non-exposed patients of same age, same treatment and identical indication. Sperm concentration and motility were compared before and after infection. Non exposure was defined by a lack of past Covid-19 diagnosis and a negative PCR throughout the treatment. Main results and the role of chance All together, including the matched cycles, we compared 40 cycles which started within 3 months of recovery: 26 fresh stimulation cycles and 14 frozen thawed transfer cycles. In 28 of these cycles the patient could serve as its own control. Mean age for the female partner was 33.2 years ±6.5 years. Eight male partners presented post infection and provided fresh samples for a cycle involving fertilization. We compared stimulation parameters including maximal Estradiol level, stimulation length, FSH dosage, number of oocytes retrieved, fertilization rates, number of embryos created, high quality embryo number and endometrial thickness. All of these were comparable to non-exposed cycles (generalized estimating equations, p values &amp;gt;0.1). No complications were recorded, specifically no thromboembolic events or respiratory complications. A total of 8 patients conceived: 1 was a chemical pregnancy, 1 extra-uterine pregnancy, 3 miscarriages and 3 ongoing, of those 1 was complicated by early bleeding. Male sperm analyses showed a trend towards lower post disease parameters, not reaching a statistical significance: 23mil/ml compared to 13.6 and 20.7% progressive motility compared to 12.3% (p values 0.09 and 0.17, respectively). Limitations, reasons for caution Current results are based on a small sample size, still insufficient for deducing definite conclusions or guidelines. Pregnancy outcome following IVF treatment in Covid-19 recoverees should further be studied. By the time of the conference, the number of cases is expected to be significantly higher. Wider implications of the findings This study provides preliminary data regarding the effects of SARS-COV-2 infection on IVF treatment outcomes. Despite the small sample size, treatment parameters seem unaffected, however, sperm performance seems to be compromised. Health policy and patients’ decisions regarding whether or not to postpone IVF procedures necessitates additional data. Trial registration number Not applicable - retrospective

Direct vs Indirect Revascularization in a North American Cohort of Moyamoya Disease.

In adults with ischemic moyamoya disease (MMD), the efficacy of direct vs indirect revascularization procedures remains a matter of debate. To investigate the outcomes of ischemic MMD in a North American cohort treated by direct and indirect revascularizations. We retrospectively reviewed medical records of adult patients with MMD with ischemic presentation from 1984 to 2018 at the Brigham and Women's Hospital and Massachusetts General Hospital who underwent either direct or indirect bypasses. Early postoperative events and outcome at more than 6 mo postoperatively were evaluated using multivariable logistic regression analyses. Multivariable Cox proportional hazards regression analyses were used to evaluate delayed ischemic and hemorrhagic events. Analyses were performed per hemisphere. A total of 95 patients with MMD and 127 hemispheres were included in this study. A total of 3.5% and 8.6% of patients had early surgical complications in the direct and indirect bypass cohorts, respectively (P=.24). Hemispheres with direct bypasses had fewer long-term ischemic and hemorrhagic events at latest follow-up (adjusted hazard ratio [HR] 0.19, 95% confidence interval [CI] 0.058-0.63, P=.007; median follow-up 4.5 [interquartile range, IQR 1-8] yr). There was no difference between the direct and indirect bypass groups when the endpoint was limited to infarction and hemorrhage only (P=.12). There was no difference in outcome (modified Rankin Scale [mRS]≥3) between the 2 cohorts (P=.92). There was no difference in early postoperative events, long-term infarction or hemorrhage, or clinical outcome between direct and indirect revascularization. However, there was a significant decrease in all ischemic and hemorrhagic events combined in direct revascularizations compared to indirect revascularizations.

Feasibility and Outcome of PSMA-PET-Based Dose-Escalated Salvage Radiotherapy Versus Conventional Salvage Radiotherapy for Patients With Recurrent Prostate Cancer.

IntroductionProstate-specific membrane antigen-positron emission tomography-(PSMA-PET) imaging facilitates dose-escalated salvage radiotherapy (DE-SRT) with simultaneous-integrated boost (SIB) for PET-positive lesions in patients with prostate cancer (PC). Therefore, we aimed to compare toxicity rates of DE-SRT with SIB to conventional SRT (C-SRT) without SIB and to report outcome.Materials and MethodsWe evaluated 199 patients who were treated with SRT between June 2014 and June 2020. 101 patients received DE-SRT with SIB for PET-positive local recurrence and/or PET-positive lymph nodes. 98 patients were treated with C-SRT to the prostate bed +/− elective pelvic lymphatic pathways without SIB. All patients received PSMA-PET imaging prior to DE-SRT ([68Ga]PSMA-11: 45.5%; [18F]-labeled PSMA: 54.5%). Toxicity rates for early (<6 months) and late (>6 months) gastrointestinal (GI) toxicities rectal bleeding, proctitis, stool incontinence, and genitourinary (GU) toxicities hematuria, cystitis, urine incontinence, urinary obstruction, and erectile dysfunction were assessed. Further, we analyzed the outcome with disease-free survival (DFS) and prostate-specific antigen (PSA) response.ResultsThe overall toxicity rates for early GI (C-SRT: 2.1%, DE-SRT: 1.0%) and late GI (C-SRT: 1.4%, DE-SRT: 5.3%) toxicities ≥ grade 2 were similar. Early GU (C-SRT: 2.1%, DE-SRT: 3.0%) and late GU (C-SRT: 11.0%, DE-SRT: 14.7%) toxicities ≥ grade 2 were comparable, as well. Early and late toxicity rates did not differ significantly between DE-SRT versus C-SRT in all subcategories (p>0.05). PSA response (PSA ≤0.2 ng/ml) in the overall group of patients with DE-SRT was 75.0% and 86.4% at first and last follow-up, respectively.ConclusionDE-SRT showed no significantly increased toxicity rates compared with C-SRT and thus is feasible. The outcome of DE-SRT showed good results. Therefore, DE-SRT with a PSMA-PET-based SIB can be considered for the personalized treatment in patients with recurrent PC.

Causes, Predictors, and Timing of Early Neurological Deterioration and Symptomatic Intracranial Hemorrhage After Administration of IV tPA.

BackgroundAcute ischemic stroke (AIS) is a major contributor toward healthcare-associated costs and services. Symptomatic intracranial hemorrhage (sICH) and early neurologic decline (END), defined as a National Health Institute Stroke Scale score decline of ≥ 4 within 24 h (with or without sICH), remain major concerns when administering intravenous tissue plasminogen activator (IV tPA) despite improved functional neurologic outcomes with its use. Given these risks, current guidelines recommend comprehensive stroke care (most often in an intensive care unit setting) for 24 h posttreatment. However, a number of patients may remain stable after IV tPA and thus not require such intensive resources. We sought to determine causes of END, along with timing and predictors of both sICH and END, to identify patients at lower risk of neurological deterioration and those suitable for earlier transition to a lower level of care.MethodsThis present study analyzed patients with AIS that presented within 4.5 h of being last seen well and received IV tPA. Baseline demographic, clinical, and radiographic findings were collected. Outcomes included END from any cause, parenchymal hemorrhage (PH1 or PH2), sICH, and mortality at 90 days.ResultsA total of 1238 patients with AIS without acute treatment of large vessel occlusion received IV tPA. 9.4% (116) had presence of any degree of ICH on noncontrast computed tomography head and 7.4% (91) experienced associated END. 2.7% (33) of patients experienced sICH, while 6.7% (83) experienced asymptomatic ICH. Of the patients with END, 63.7% did not have ICH. Predictive factors at presentation for END included an older age (72.6 ± 16.1 vs. 69.1 ± 14.8, p = 0.03), history of tobacco use (odds ratio [OR] 2.1 [1.1–4.3], p = 0.04), and hyperlipidemia (OR 1.7 [1.1–2.8], p = 0.02), along with the presence of an untreated large vessel occlusion (OR 2.1 [1.4–3.1], p = 0.02). Most END occurred within a mean time of 242 ± 251 min (4 ± 4 h). Because of the small proportion of patients suffering from sICH (33), predictors could not be determined; however, for patients with any ICH, predictive factors included an older age (74.6 ± 12.4 vs. 68.8 ± 15.1, p = 0.001), higher baseline National Health Institute Stroke Scale score (14.6 ± 7.3 vs. 10.8 ± 7.9, p = 0.002), and higher baseline glucose levels (155.1 ± 87.5 vs. 140.4 ± 70.5, p = 0.04).ConclusionsIn this study, only a small proportion suffered from either sICH and/or END, typically within 12 h of tPA administration. These findings may support earlier deescalation of higher acuity monitoring in clinically stable post-IV tPA patients without large vessel occlusion.

An Original Risk Score to Predict Early Major Bleeding in Acute Pulmonary Embolism: The Syncope, Anemia, Renal Dysfunction (PE-SARD) Bleeding Score

Improved prediction of the risk of early major bleeding in pulmonary embolism (PE) is needed to optimize acute management. Does a simple scoring system predict early major bleeding in acute PE patients, identifying patients with either high or low probability of early major bleeding? From a multicenter prospective registry including 2,754 patients, we performed post hoc multivariable logistic regression analysis to build a risk score to predict early (up to hospital discharge) major bleeding events. We validated the endpoint model internally, using bootstrapping in the derivation dataset by sampling with replacement for 500 iterations. Performances of this novel score were compared with that of the VTE-BLEED (Venous Thrombo-Embolism Bleed), RIETE (Registro informatizado de la enfermedad tromboembólica en España; Computerized Registry of Patients with Venous Thromboembolism), and BACS (Bleeding, Age, Cancer, and Syncope) models. Multivariable regression identified three predictors for the occurrence of 82 major bleeds (3.0%; 95%CI, 2.39%-3.72%): Syncope (+1.5); Anemia, defined as hemoglobin<12 g/dL (+2.5); and Renal Dysfunction, defined as glomerular filtration rate<60mL/min (+1 point) (SARD). The PE-SARD bleeding score was calculated by summing all the components. Overall, 52.2%(95%CI, 50.29%-54.11%) of patients were classified as low bleeding-risk (score, 0 point), 35.2%(95%CI, 33.39%-37.04%) intermediate-risk (score, 1-2.5 points), and 12.6%(95%CI, 9.30%-16.56%) high-risk (score >2.5 points). Observed bleeding rates increased with increasing risk group, from 0.97%(95%CI, 0.53%-1.62%) in the low-risk to 8.93%(95%CI, 6.15%-12.44%) in the high-risk group. C-index was 0.74 (95%CI, 0.73-0.76) and Brier score 0.028 in the derivation cohort. Similar values were calculated from internal bootstrapping. Performance of the PE-SARD score was better than that observed with the VTE-BLEED, RIETE, and BACS scores, leading to a high proportion of bleeding-risk reclassification in patients who bled and those who did not. The PE-SARD bleeding risk score is an original, user-friendly score to estimate risk of early major bleeding in patients with acute PE.

Prediction of Major Bleeding in Anticoagulated Patients for Venous Thromboembolism: Comparison of the RIETE and the VTE-BLEED Scores

The performance of validated bleeding risk scores in patients with venous thromboembolism (VTE) could be different depending on the time after index event or the site of bleeding. In this study we compared the “classic” Registro Informatizado de Enfermedad TromboEmbólica (RIETE) score and the more recently developed VTE-BLEED score for the prediction of major bleeding in patients under anticoagulant therapy in different time intervals after VTE diagnosis. Out of 82,239 patients with acute VTE, the proportion of high-risk patients according to the RIETE and VTE-BLEED scores was 7.1 and 62.3%, respectively. The performance of both scores across the different study periods (first 30 days after VTE diagnosis, days 31–90, days 91–180, and days 181–360) was similar, with areas under the receiving operating characteristics (ROC) curve (AUC) ranging between 0.69 and 0.72. However, the positive predictive values were low, ranging between 0.6 and 3.9 (better for early major bleeding than for later periods). A sensitivity analysis limited to patients with unprovoked VTE showed comparable results. Both scores showed a trend toward a better prediction of extracranial than intracranial major bleeding, the RIETE score resulting more useful for early extracranial bleeding and the VTE-BLEED for late intracranial hemorrhages. Our study reveals that the usefulness of available bleeding scores may vary depending on the characteristics of the patient population and the time frame evaluated. Dynamic scores could be more useful for this purpose.

Applying Metal Clips at the Tip of Gastrojejunostomy Stapling Site to Reduce Intraluminal Early Postoperative Bleeding

Nowadays, surgical option is the most powerful and durable treatment modality for morbid obese patients in the world. Postoperative Gastrointestinal bleeding is one of complications which has been encountered in the early and late postoperative period after bariatric surgery. One of probable locations of gastrointestinal bleeding after gastric bypass is gastrojejunostomy anastomosis site. Use of metal clips in the tip of inner aspect of gastrojejunostomy anastomosis may reduce intraluminal bleeding in early postoperative period.

The FAST VIP (First Aid for Severe Trauma "Virtual" in-Person) Educational Study.

IntroductionTrauma is the leading cause of death for young Americans. Increased school violence, combined with an emphasis on early hemorrhage control, has boosted demand to treat injuries in schools. Meanwhile, coronavirus disease 2019 (COVID-19) has made educating the public about trauma more difficult. A federally funded high school education program in development, called First Aid for Severe Trauma™ (FAST™), will teach students to aid the severely injured. The program will be offered in instructor-led, web-based, and blended formats. We created a program to prepare high school teachers to become FAST instructors via “virtual” in-person (VIP) instruction. We used a webinar followed by VIP skills practice, using supplies shipped to participants’ homes. To our knowledge, no prior studies have evaluated this type of mass, widely distributed, VIP education.MethodsThis study is a prospective, single-arm, educational cohort study. We enrolled a convenience sample of all high school teachers attending FAST sessions at the Health Occupations Students of America–Future Health Professionals International Leadership Conference. Half of the participants were randomized to complete the Stop the Bleed Education Assessment Tool (SBEAT) prior to the webinar, and the other completed it afterward; SBEAT is a validated tool to measure learning of bleeding competencies. We then performed 76 VIP video-training sessions from June–August 2020. The FAST instructors assessed each participant’s ability to apply a tourniquet and direct pressure individually, then provided interactive group skills training, and finally re-evaluated each participant’s performance post-training.ResultsA total of 190 (96%) participants successfully applied a tourniquet after VIP training, compared to 136 (68%) prior to training (P < 0.001). Participants significantly improved their ability to apply direct pressure: 116 (56%) pre-assessment vs 204 (100%) post-assessment (P < 0.001). The mean score for the SBEAT increased significantly from pre-training to post-training: 2.09 with a standard deviation (SD) of 0.97 to 2.55 post-training with a SD of 0.72 (P < 0.001).ConclusionThis study suggests that a webinar combined with VIP training is effective for teaching tourniquet and direct-pressure application skills, as well as life-threatening bleeding knowledge. VIP education may be useful for creating resuscitative medicine instructors from distributed locations, and to reach learners who cannot attend classroom-based instruction.

Recombinant Human Thrombopoietin (rhTPO) and High-Dose Dexamethasone (HD-DXM) Versus High-Dose Dexamethasone Monotherapy As Frontline Treatment in Newly Diagnosed Adult Immune Thrombocytopenia (ITP): a Prospective, Multicentre, Randomised, Controlled Trial

Introduction: Immune thrombocytopenia (ITP) is an acquired thrombocytopenia and caused by immune-mediated platelet destruction and impaired platelet production. Corticosteroids are recommended as the standard first-line treatment. As the immunosuppressive therapy,HD-DXM could decrease platelet destruction by regulating T cell immune abnormalities. Thrombopoietin (TPO) is the primary regulator of thrombopoiesis. Several studies have proved that TPO have profound effects on megakaryocyte development and platelet production as well as restore immune tolerance. We suppose the rhTPO and HD-DXM could work synergistically based on these mechanisms. Recently, several pilot studies have examined the efficacy and safety of TPO-RA in treatment-naive adult ITP patients. We present the results of the first prospective,multicenter,randomized,controlled trial on the largest cohort to date comparing the efficacy and safety of HD-DXM plus rhTPO vs HD-DXM as frontline therapy in newly diagnosed adult primary ITP patients.Methods: Between July 2013 and December 2016, 245 newly-diagnosed, treatment-naive ITP patients aged 18-75 years in 25 separate centers in China were enrolled in the trial (NCT01734044). DXM was administered orally at 40 mg daily for 4 consecutive days to both arms. The 4-day course of dexamethasone was repeated on days 11 to 14 in the case of lack of response. Patients in the experimental arm received subcutaneously rhTPO at a daily dose of 300U/kg concomitantly during the first 14 days. Patients with platelet counts higher than 100×109/L or more than 50×109/L increase of the baseline platelet count could discontinue the rhTPO treatments. Use of rescue treatments such as platelet transfusion and hemostatic agents were allowed at the discretion of the investigator if the platelet count <10×109/L or ≥10×109/L with active bleeding and were recorded. Patients were assessed at day 14. Study visits were scheduled every 1 month until the end of the 6th month or day of relapse. The primary endpoint was the early response rates at day 14 (OR: platelet count ≥30×109/L and at least 2-fold increase of the baseline platelet count and absence of bleeding, CR: platelet count ≥100×109/L). Key secondary endpoints were rates of sustain response and complete response at the end of month 6, duration of response (DOR), bleeding scores, assessments of adverse events (AEs). Any administration of additional ITP specific medication or withdrawn from the study because of no response was regarded as nonresponders.Results: 196 patients were randomly to receive HD-DXM with (n=100) or without (n=96) rhTPO. Demographics and baseline characteristics were balanced between the 2 arms. HD-DXM+ rhTPO resulted in a higher incidence of early OR at day 14 compared with HD-DXM monotherapy (89.0% vs 66.7%, P<0.001, table 1), the CR rate were 75.0% (HD-DXM+ rhTPO) vs 42.7% (HD-DXM) (P<0.001). Sustained OR and CR at the end of the 6th month was also higher in patients treated with HD-DXM+ rhTPO than in those treated with HD-DXM alone (OR: 51.0% vs 36.5%, P=0.022; CR: 46.0% vs 32.3%, P=0.043, table 1). Throughout the follow-up period, overall duration of response was greater in the experimental group, estimated by the Kaplan-Meier analysis (Figure 1, P=0.04). There was no difference between these 2 groups in terms of TTR, bleeding scores and rescue treatments. No statistically significant differences were observed in the incidence of treatment-related AEs between the two groups. Three patients had grade 4 or higher AEs in the HD-DXM+ rhTPO group, including early cerebral hemorrhage (n=2) and cerebral infarction (n=1); none were deemed treatment-related, one patient in the rhTPO group died of early cerebral hemorrhage. No patient was tested positive for neutralizing antibodies against TPO.Conclusions: Our findings suggest that the addition of rhTPO to HD-DXM is superior to HD-DXM monotherapy in the treatment of newly diagnosed treatment-naive adult ITP patients. Thus, this combination can be a feasible frontline therapy in adult ITP. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.