Local carbachol application induces oral microvascular recruitment and improves gastric tissue oxygenation during hemorrhagic shock in dogs.

Introduction: Hemorrhagic shock is characterized by derangements of the gastrointestinal microcirculation. Topical therapy with nitroglycerine or iloprost improves gastric tissue oxygenation but not regional perfusion, probably due to precapillary adrenergic innervation. Therefore, this study was designed to investigate the local effect of the parasympathomimetic carbachol alone and in combination with either nitroglycerine or iloprost on gastric and oral microcirculation during hemorrhagic shock. Methods: In a cross-over design five female foxhounds were repeatedly randomized into six experimental groups. Carbachol, or carbachol in combination with either nitroglycerine or iloprost were applied topically to the oral and gastric mucosa. Saline, nitroglycerine, or iloprost application alone served as control groups. Then, a fixed-volume hemorrhage was induced by arterial blood withdrawal followed by blood retransfusion after 1h of shock. Gastric and oral microcirculation was determined using reflectance spectrophotometry and laser Doppler flowmetry. Oral microcirculation was visualized with videomicroscopy. Statistics: 2-way-ANOVA for repeated measurements and Bonferroni post-hoc analysis (mean ± SEM; p < 0.05). Results: The induction of hemorrhage led to a decrease of gastric and oral tissue oxygenation, that was ameliorated by local carbachol and nitroglycerine application at the gastric mucosa. The sole use of local iloprost did not improve gastric tissue oxygenation but could be supplemented by local carbachol treatment. Adding carbachol to nitroglycerine did not further increase gastric tissue oxygenation. Gastric microvascular blood flow remained unchanged in all experimental groups. Oral microvascular blood flow, microvascular flow index and total vessel density decreased during shock. Local carbachol supply improved oral vessel density during shock and oral microvascular flow index in the late course of hemorrhage. Conclusion: The specific effect of shifting the autonomous balance by local carbachol treatment on microcirculatory variables varies between parts of the gastrointestinal tract. Contrary to our expectations, the improvement of gastric tissue oxygenation by local carbachol or nitroglycerine application was not related to increased microvascular perfusion. When carbachol is used in combination with local vasodilators, the additional effect on gastric tissue oxygenation depends on the specific drug combination. Therefore, modulation of tissue oxygen consumption, mitochondrial function or alterations in regional blood flow distribution should be investigated.

Resuscitation and Care in the Trauma Bay.

Start balanced resuscitation early (pre-hospital if possible), either in the form of whole blood or 1:1:1 ratio. Minimize resuscitation with crystalloid to minimize patient morbidity and mortality. Trauma-induced coagulopathy can be largely avoided with the use of balanced resuscitation, permissive hypotension, and minimized time to hemostasis. Using protocolized "triggers" for massive and ultramassive transfusion will assist in minimizing delays in transfusion of products, achieving balanced ratios, and avoiding trauma induced coagulopathy. Once "audible" bleeding has been addressed, further blood product resuscitation and adjunct replacement should be guided by viscoelastic testing. Early transfusion of whole blood can reduce patient morbidity, mortality, decreases donor exposure, and reduces nursing logistics during transfusions. Adjuncts to resuscitation should be guided by laboratory testing and carefully developed, institution-specific guidelines. These include empiric calcium replacement, tranexamic acid (or other anti-fibrinolytics), and fibrinogen supplementation.

Toward Genetic Testing of Rivaroxaban? Insights from a Systematic Review on the Role of Genetic Polymorphism in Rivaroxaban Therapy.

BACKGROUND: Investigations into the rivaroxaban response from the perspective of genetic variation have been relatively recent and wide in scope, whereas there is no consensus on the necessity of genetic testing of rivaroxaban. Thus, this systematic review aims to thoroughly evaluate the relationship between genetic polymorphisms and rivaroxaban outcomes. METHODS: The PubMed, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), and Chinese databases were searched to 23 October 2022. We included cohort studies reporting the pharmacogenetic correlation of rivaroxaban. Outcomes measured included efficacy (all-cause mortality, thromboembolic events and coagulation-related tests), safety (major bleeding, clinically relevant non-major bleeding [CRNMB] and any hemorrhage), and pharmacokinetic outcomes. A narrative synthesis was performed to summarize findings from individual studies according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses and the reporting guideline for Synthesis Without Meta-Analysis. RESULTS: A total of 12 studies published between 2019 and 2022 involving 1364 patients were included. Ten, one, and six studies focused on the ABCB1, ABCG2, and CYP gene polymorphisms, respectively. Pharmacokinetic outcomes accounted for the majority of the outcomes reported (n = 11), followed by efficacy (n = 5) [including prothrombin time (PT) or international normalized ratio (n = 3), platelet inhibition rate (PIR) or platelet reactivity units (PRUs; n = 1), thromboembolic events (n = 1)], and safety (n = 5) [including major bleeding (n = 2), CRNMB (n = 2), any hemorrhage (n = 1)]. For ABCB1 gene polymorphism, the relationship between PT and ABCB1 rs1045642 was inconsistent across studies, however there was no pharmacogenetic relationship with other efficacy outcomes. Safety associations were found in ABCB1 rs4148738 and major bleeding, ABCB1 rs4148738 and CRNMB, ABCB1 rs1045642 and CRNMB, and ABCB1 rs2032582 and hemorrhage. Pharmacokinetic results were inconsistent among studies. For ABCG2 gene polymorphism, no correlation was observed between ABCG2 rs2231142 and dose-adjusted trough concentration (Cmin/D). For CYP gene polymorphisms, PIR or PRUs have a relationship with CYP2C19 rs12248560, however bleeding or pharmacokinetic effects did not show similar results. CONCLUSIONS: Currently available data are insufficient to confirm the relationship between clinical or pharmacokinetic outcomes of rivaroxaban and gene polymorphisms. Proactive strategies are advised as a priority in clinical practice rather than detection of SNP genotyping. CLINICAL TRIALS REGISTRATION: PROSPERO registration number CRD42022347907.

Clot time ratio (CTR) and treatment outcomes in Apixaban-treated atrial fibrillation patients.

There are clinical situations where information about the anticoagulant effects of Apixaban could be useful. Specialised methods for measuring Apixaban concentrations are not available at all medical laboratories while methods for measuring the functional effects of Apixaban, using clot time ratio (CTR), can be performed in most medical laboratories around the clock using well-established measurement procedures. The aim of this study was to investigate CTR in trough and peak samples during Apixaban treatment of atrial fibrillation and to correlate the findings to bleeds and thrombotic events. Three trough- and three peak samples from 61 patients (31 on Apixaban 5 mg twice daily and 30 on Apixaban 2.5 mg twice daily) were analysed with MRX PT DOAC. Patients were followed for 30 + /-15 months, and bleeds and thrombotic events were documented. The effect of Apixaban could be measured with MRX PT DOAC and there was a statistically significant difference between CTR in trough samples compared to peak samples (p < 0.001). A total of 21 patients suffered bleeds during follow-up; two patients suffered major bleeds, and 19 suffered minor bleeds. Patients with major bleeds had both mean peak- and mean trough CTR above the respective first to third quartile (Q1-Q3) range. Four patients suffered thromboembolic events. Generally, the peak CTRs were below or in the lower end of the peak Q1-Q3 for these patients. The new test MRX PT DOAC can be used to measure the effect of Apixaban during the treatment of atrial fibrillation. High mean peak- and mean trough CTR were seen in 2 patients with major bleeds, and low peak CTR was seen in 4 patients with thromboembolic events.

Incidence and Costs of Clinically Significant Events with Systemic Therapy in Patients with Unresectable Hepatocellular Carcinoma: A Retrospective Cohort Study.

INTRODUCTION: Systemic therapies have been associated with clinically significant events (CSEs) in patients with unresectable hepatocellular carcinoma (uHCC). We evaluated the incidence of CSEs (bleeding, clotting, encephalopathy, and portal hypertension), and their impact on healthcare resource utilization (HCRU) and costs, in patients with uHCC treated with first-line (1L) atezolizumab plus bevacizumab (A + B), lenvatinib (LEN), or sorafenib (SOR) in the USA. METHODS: A retrospective cohort study was performed using medical/pharmacy claims from Optum® Clinformatics® Data Mart. Patients diagnosed with HCC who initiated 1L A + B between June 01, 2020 and December 31, 2020 or LEN/SOR between January 01, 2016 and May 31, 2020 were included. Outcomes included incidence rates of CSEs, HCRU, and costs. Subgroup analysis was performed in patients with no CSEs or ≥ 1 CSE. RESULTS: In total, 1379 patients were selected (A + B, n = 271; LEN, n = 217; SOR, n = 891). Clotting (incidence rate per 100 patient-years [PY] 94.9) and bleeding (88.1 per 100 PY) were the most common CSEs in the A + B cohort. The most common CSEs in the LEN cohort were clotting (78.6 per 100 PY) and encephalopathy (66.3 per 100 PY). Encephalopathy (73.0 per 100 PY) and portal hypertension (72.3 per 100 PY) were the most common CSEs in the SOR cohort. Mean total all-cause healthcare costs per patient per month (PPPM) were $32,742, $35,623, and $29,173 in the A + B, LEN, and SOR cohorts, respectively. Mean total all-cause healthcare costs PPPM were higher in patients who had ≥ 1 CSE versus those who did not (A + B $34,304 versus $30,889; LEN $39,591 versus $30,621; SOR $31,022 versus $27,003). CONCLUSION: Despite improved efficacy of 1L systemic therapies, CSEs remain a concern for patients with uHCC, as well as an economic burden to the healthcare system. Newer treatments that reduce the risk of CSEs, while improving long-term survival in patients with uHCC, are warranted.

Certain treatments for liver cancer can cause serious side effects, including bleeding, blood clots, brain injury (encephalopathy), or increased blood flow to the liver (portal hypertension). We used an insurance database to find out how often these events, known as clinically significant events, occurred in people with liver cancer who were given treatments that target the immune system (immunotherapy) or specific proteins involved in cancer growth and survival (targeted therapy). The study included 1379 patients treated with atezolizumab (immunotherapy) plus bevacizumab (targeted therapy), or lenvatinib or sorafenib alone (both targeted therapies), as their first treatment. Clotting and bleeding were the most common clinically significant events in patients treated with atezolizumab plus bevacizumab, whereas clotting and encephalopathy were the most common clinically significant events with lenvatinib, and encephalopathy and portal hypertension were the most common clinically significant events with sorafenib. On average, for every 100 patients treated for 1 year, there were more than 50 of each of these events. Average healthcare costs per patient per month ranged from around $29,000 to around $36,000 in the three different treatment groups, and were higher in people who had at least one clinically significant event. These results suggest that clinically significant events are common in people with liver cancer who are given various types of treatment. As well as raising concerns for patient safety, these events result in higher costs to healthcare systems. Therefore, newer treatments that are less likely to cause clinically significant events, while improving survival in patients with liver cancer, are needed.

Granular Hemostatic Composite of Alginate, Calcium, and Zinc for Rapid and Effective Management of Post-Traumatic Hemorrhage.

Post-traumatic hemorrhage, which can result from accidents or battlefield injuries, is a significant global concern due to the high prehospital mortality rate. Substantial efforts have been made to develop hemostatic agents that can effectively reduce hemorrhage in the immediate aftermath of a traumatic event. The present study investigated the potential efficacy of Ca2+ and Zn2+ supplemented sodium alginate-based dry hemostatic particles (SA-CZ DHP) to manage excessive blood loss or post-traumatic hemorrhage. SA-CZ DHP were developed, followed by their physical and biochemical characterization, cytocompatibility and hemocompatibility testing, and critical evaluation of the hemostatic potential in vitro and in vivo. The safe SA-CZ DHP showed high absorption and accelerated blood clotting kinetics with reduced coagulation time (≈70%, p < 0.0001) in whole human blood, observed with insignificant hemolysis and uninterrupted RBC morphology. SA-CZ DHP significantly reduced the mean blood loss (≈90% in SD rats tail incision), and bleeding time (≈60% in BALB/c mice tail incision) was at par with commercially available Celox hemostatic granules. In conclusion, the biocompatible SA-CZ DHP exhibited rapid and effective management of excessive blood loss. It is also pertinent to note that the developed formulation could be a cost-effective alternative to its commercial counterparts.

The psychological intervention and clinical efficacy of Rosenthal effect and acupuncture bleeding on middle-aged and young patients with sudden hearing loss.

Combining traditional Chinese medicine theory and modern medical knowledge, this study explores the pathogenesis of sudden hearing loss in middle-aged and young people. Sixty-four young and middle-aged patients with sudden hearing loss who visited a public tertiary hospital in China are chosen as experimental objects. All experimental patients are broken into an experimental group (n = 32) and a control group (n = 32). The control group receive conventional Western medicine treatment regimen. The experimental group receive select acupoint acupuncture and bloodletting combined with Rosenthal effect for psychological intervention, and both groups have a treatment course of 14 days. The changes in the patient's condition before and after treatment are observed, and the differences in hearing threshold values, tinnitus, and dizziness clinical efficacy before and after treatment are observed and recorded. It evaluates the efficacy using the Anxiety, Depression Scale, and Hope Scale and statistically analyzes the data. The dizziness score of the experimental group decreased rapidly, the treatment onset time was shorter, and the improvement effect on dizziness symptoms was better (P < .05). After 1 month of intervention treatment, the intervention of the experimental group was better (P < .05). The hope level and self-efficacy of both groups of patients were raised in contrast with before treatment (P < .05). After 1 month, the intervention effect of the experimental group was more significant (P < .01). Both groups could improve patient ear blood circulation, but the experimental group had lower plasma viscosity, hematocrit, and red blood cell aggregation index, higher red blood cell deformation index, and more significant improvement effect (P < .05). The effective rates of improving hearing and tinnitus in the experimental group reached 87.5% and 81.5%, and the clinical treatment efficacy was better than that in the control group (P < .05). The level of depression and anxiety in the experimental group remained relatively stable, while that in the control group showed a significant rebound (P < .05). In conclusion, both groups had a certain effect in treating sudden deafness, both of which could effectively improve the patient's hearing. But in contrast with the control group, the experimental group had better clinical efficacy, higher safety, and better psychological intervention results, which is worthy of clinical promotion.

Topical and subconjunctival anesthesia versus topical anesthesia alone in patients with senile cataracts undergoing phacoemulsification: a double-blind randomized controlled trial.

BACKGROUND: This study compared topical anesthesia to a combination of topical anesthesia and subconjunctival anesthesia for phacoemulsification. METHODS: This double-blinded parallel placebo-controlled randomized trial involved senile cataract patients scheduled for phacoemulsification between May and December 2022. Patients were randomly assigned to receive either topical anesthesia with 0.5% tetracaine hydrochloride and subconjunctival balanced salt solution injection (Control group) or topical anesthesia and subconjunctival injection with 2% lidocaine (Lidocaine group). Baseline parameters, cataract grades, and various outcomes were recorded, including pain scores at specific time points, patient cooperation scores, requests for additional anesthesia, and complications. Statistical methods included Fisher's exact test, the t-test, ordinal logistic regression, and linear regression with robust standard errors. RESULTS: In total, 176 patients were included in the study after excluding 33 patients. A significant reduction in immediate postoperative pain was achieved in the Lidocaine group (p < 0.001) and was maintained for 2 h (p = 0.011). Additionally, better cooperation was observed in this group (p = 0.038). However, patients in the Lidocaine group experienced more pain during the subconjunctival injection (p = 0.001) and a significant increase in subconjunctival hemorrhage related to the injection (p < 0.001). Despite this, the rates of surgical complications were comparable between the groups, and all phacoemulsification procedures were successfully completed using the assigned anesthetic technique. CONCLUSIONS: The addition of subconjunctival lidocaine injection to topical anesthesia reduced postoperative pain and improved patient cooperation during phacoemulsification. However, the lidocaine injection was painful, and it carried a higher risk of spontaneous-relief subconjunctival hemorrhage. TRIAL REGISTRATION: Trial Registration Number: TCTR20220804003, date of registration August 4, 2022, retrospectively registered.

Acupuncture-Induced Hemothorax with Hypovolemic Shock: A Case Report.

This report describes a very rare but life-threatening complication that occurred in a 43-year-old woman after an acupuncture (AC) for lumbago. The patient presented to the emergency department displaying symptoms indicative of shock. Physical examination revealed the absence of breath sounds on the right thoracic side, further investigations indicated the presence of a hemothorax. Emergency surgery was performed to evacuate the hemothorax and control bleeding from two intercostal veins. Although AC is often considered a gentle form of medicine, it is important to recognize that it can occasionally result in severe complications, especially when acupoints are used on the thorax.

Safety outcomes of direct oral anticoagulants in older adults with atrial fibrillation: a systematic review and meta-analysis of (subgroup analyses from) randomized controlled trials.

Balancing stroke prevention and risk of bleeding in patients with atrial fibrillation (AF) is challenging. Direct oral anticoagulants (DOACs) are by now considered standard of care for treating patients with AF in international guidelines. Our objective was to assess the safety of long-term intake of DOACs in older adults with AF. We included RCTs in elderly (≥ 65 years) patients with AF. A systematic search in MEDLINE and EMBASE was performed on 19 April 2022. For determination of risk of bias, the RoB 2 tool was applied. We pooled outcomes using random-effects meta-analyses. The quality of evidence was assessed using GRADE. Eleven RCTs with a total of 63,374 patients were identified. Two RCTs compared apixaban with either warfarin or aspirin, four edoxaban with either placebo, aspirin, or vitamin K antagonists (VKAs), two dabigatran with warfarin and three rivaroxaban with warfarin. DOACs probably reduce mortality in elderly patients with AF (HR 0.89 95%CI 0.77 to 1.02). Low-dose DOACs likely reduce bleeding compared to VKAs (HR ranged from 0.47 to 1.01). For high-dose DOACS the risk of bleeding varied widely (HR ranged from 0.80 to 1.40). We found that low-dose DOACs probably decrease mortality in AF patients. Moreover, apixaban and probably edoxaban are associated with fewer major or clinically relevant bleeding (MCRB) events compared to VKAs. For dabigatran and rivaroxaban, the risk of MCRB varies depending on dose. Moreover, subgroup analyses indicate that in the very old (≥ 85) the risk for MCRB events might be increased when using DOACs.Registration: PROSPERO: CRD42020187876.

Bleeding Risk of Acupuncture for Patients with Hematological Malignancies Accompanying Thrombocytopenia: A Retrospective Chart Review.

Introduction: In recent years, it has been reported that acupuncture is useful for alleviating the symptoms of patients with hematological malignancies, but the safety of acupuncture for such patients has not been established. This study evaluated the risk of bleeding from acupuncture in patients with hematological malignancies accompanying thrombocytopenia. Methods: The authors performed a retrospective investigation of the medical records of patients with hematological malignancies who received acupuncture during hospitalization at the hematology department of a single medical center in Japan. The bleeding risk at the acupuncture site was evaluated in the following four groups according to the platelet count measured on the day of acupuncture treatment: (1) <20 × 103/µL, (2) 20-49 × 103/µL, (3) 50-99 × 103/µL, and (4) 100 × 103/µL or more. Occurrence of grade 2 or higher bleeding according to the Common Terminology Criteria for Adverse Events, version 5.0, within 24 h from the acupuncture session or before the next session was defined as an event, and the risk of occurrence of bleeding was examined in each group. Results: Of 2423 acupuncture sessions conducted on 51 patients with hematological malignancies, 815 were included in the analysis. Ninety sessions were performed in the <20 × 103/µL platelet count group, 161 in the 20-49 × 103/µL group, 133 in the 50-99 × 103/µL group, and 431 in the 100 × 103/µL or more group. No bleeding event according to the authors' definition occurred in any of these groups. Conclusions: This study is the largest to date to assess the bleeding risk of acupuncture in patients with hematological malignancies accompanying thrombocytopenia. The authors considered that acupuncture could be safely performed without causing serious bleeding for patients with hematological malignancies accompanying thrombocytopenia.

Risk of Incident Atrial Fibrillation and Subsequent Use of Oral Anticoagulants in Patients with Dementia.

BACKGROUND: Dementia and atrial fibrillation (AF) have many shared risk factors. Besides, patients with dementia are under-represented in randomized trials, and even if AF is present, oral anticoagulants (OACs) are not prescribed frequently. This study aimed to report the incidence of newly diagnosed AF in dementia patients, and the impacts of use of vitamin K antagonist (VKA; e.g., warfarin) and non-VKA OAC (NOACs) on stroke and bleeding outcomes. METHODS: Our study utilized the Taiwan National Health Insurance Research Database. A total of 554,074 patients with dementia were compared with 554,074 age- and sex-matched patients without dementia regarding the risk of incident AF. Among patients with dementia who experienced incident AF, the risks of clinical events of patients treated with warfarin or NOACs were compared with those without OACs (reference group). RESULTS: The risk of incident AF was greater for patients with dementia compared with those without (adjusted hazard ratio [aHR]: 1.054; 95% confidence interval [CI]: 1.040-1.068 for all types of dementia, aHR: 1.035; 95% CI: 1.020-1.051 for presenile/senile dementia, and aHR: 1.125; 95% CI: 1.091-1.159 for vascular dementia). Among patients with dementia and experienced incident AF, warfarin use was associated with a higher risk of ischemic stroke (aHR: 1.290; 95% CI: 1.156-1.440), intracranial hemorrhage (ICH; aHR: 1.678; 95% CI: 1.346-2.090), and major bleeding (aHR: 1.192; 95% CI: 1.073-1.323) compared with non-OACs. NOAC use was associated with a lower risk of ischemic stroke (aHR: 0.421; 95% CI: 0.352-0.503) and composite risk of ischemic stroke or major bleeding (aHR: 0.544; 95% CI: 0.487-0.608) compared with non-OACs. These results were consistent among the patients after the propensity matching. CONCLUSION: In this large nationwide cohort, the risk of newly diagnosed AF was higher in patients with dementia (all dementia, presenile/senile dementia, and vascular dementia) compared with those without dementia. For patients with dementia who experienced incident AF, NOAC use was associated with a better clinical outcome compared with non-OAC. Patients with dementia require a holistic approach to their care and management, including the use of NOACs to reduce the risks of clinical events.

Effect of spiritual care on the quality of life in patients who underwent intracranial hemorrhage surgery: a randomized controlled trial.

INTRODUCTION: One of the most important complications of stroke after intracranial haemorrhage surgery is impaired quality of life. This study was conducted to determine the impact of spiritual care on the quality of life of stroke patients. METHODS: This single-blind clinical trial with a pre-test and post-test design was conducted on 100 stroke patients. Participants were recruited and randomly assigned to a control group and an intervention group. The stroke-specific quality of life (SS -QoL) scale was used to assess the quality of life of stroke patients. The intervention group received four sessions of spiritual care. RESULTS: The independent t -test showed no significant difference between the two groups in the mean quality of life score ( t =-0.120, P =0.281) and its dimensions before the intervention. However, after the intervention, the results showed a significant difference between the two groups in terms of the mean quality of life score ( t =1.984, P <0.001) and its dimensions. In addition, the results of the paired t -test showed that in the intervention group, the mean score of quality of life ( t =5.161, P <0.001) and its dimensions were significantly different before and after the intervention. Furthermore, the results showed that before and after the intervention in the control group, the mean score of quality of life ( t =1.109, P =0.614) and its dimensions were not significantly different. CONCLUSIONS: Based on this results, the authors strongly recommend the use of spiritual care as a holistic care and complementary method to improve the symptoms and quality of life of stroke patients.

Utilizing epoxy Bletilla striata polysaccharide collagen sponge for hemostatic care and wound healing.

Hemostatic materials that are lightweight and possess good blood absorption performance have been widely considered for use in modern wound care. Natural hemostatic ingredients derived from traditional Chinese medicine have also received extensive attention. Bletilla polysaccharides are valued by researchers for their excellent hemostatic performance and good reactivity. Collagen is favored by researchers due to its high biocompatibility and low immunogenicity. In this study, Bletilla striata polysaccharide, the main hemostatic component of Bletilla striata, was activated by epoxy groups, and epoxidized Bletilla striata polysaccharide (EBSP) was prepared. Then, EBSP was crosslinked with collagen under alkaline conditions, and a new hemostatic material that was an epoxidized Bletilla polysaccharide crosslinked collagen hemostatic sponge was prepared. We demonstrated that endowing collagen with better hemostatic performance, cytocompatibility, and blood compatibility does not destroy its original three-stranded helical structure. Compared with the medical gauze, hemostasis time was shorter (26.75 ±â€¯2.38 s), and blood loss was lower (0.088 ±â€¯0.051 g) in the rat liver injury hemostasis model. In the rat model of severed tail hemostasis, hemostasis time was also shorter (47.33 ±â€¯2.05 s), and the amount of blood loss was lower (0.330 ±â€¯0.122 g). The sponge possessed good hemostatic and healing performance.

Dual antithrombotic therapy dose-dependently alters hemostatic plug structure and function.

BACKGROUND: Antithrombotic medications carry an inherent risk of bleeding, which may be exacerbated when anticoagulant and antiplatelet therapeutics are combined. Prior studies have shown different effects of antiplatelet vs anticoagulant drugs on the structure and function of hemostatic plugs in vivo. OBJECTIVES: We examined whether dual antithrombotic treatment consisting of combined antiplatelet and anticoagulant therapeutics alters hemostatic plug structure and function differently from treatment with either therapeutic alone. METHODS: Mice were treated with the P2Y12 antagonist clopidogrel and the factor Xa inhibitor rivaroxaban across a range of doses, either alone or in combination. The hemostatic response was assessed using a mouse jugular vein puncture injury model. Platelet accumulation and fibrin deposition were evaluated using quantitative multiphoton fluorescence microscopy, and bleeding times were recorded. RESULTS: Mice treated with clopidogrel alone exhibited a decrease in platelet accumulation at the site of injury, with prolonged bleeding times only at the highest doses of clopidogrel used. Mice treated with rivaroxaban alone instead showed a reduction in fibrin deposition with no impact on bleeding. Mice treated with both clopidogrel and rivaroxaban exhibited platelet and fibrin accumulation that was similar to that with either drug given alone; however, dual antithrombotic therapy resulted in impaired hemostasis at doses that had no impact on bleeding when given in isolation. CONCLUSION: Combined administration of antiplatelet and anticoagulant therapeutics exacerbates bleeding as compared to that with either drug alone, potentially via combined loss of both adenosine 5'-diphosphate- and thrombin-mediated platelet activation. These findings enhance our understanding of the bleeding risk associated with dual antithrombotic therapy.

Instructional and didactic support tool for teaching-learning Post-Partum Haemorrhage care in simulated settings: Creation and validation.

OBJECTIVE: To describe the creation and validation process of an instructional, didactic and self-applied support tool for teaching-learning Post-Partum Haemorrhage care in simulated settings. BACKGROUND: Students frequently face difficulties performing the actions in the proper sequence in Post-Partum Haemorrhage simulated cases. Even in a controlled environment, anxiety, nervousness and fear of making mistakes are evident, which render the simulated experience highly stressful. Having a tool with a guideline can help students perform these actions more assertively. DESIGN: A methodological study to develop a didactic tool. METHODS: The creation process of the didactic tool, called Instructional Disk for the Management of Post-Partum Haemorrhage, was divided into five phases: Analysis, Design, Development, Implementation and Evaluation. Nine experts specialised in Obstetrics and Midwifery validated the tool by answering a questionnaire with nine items; in turn, 32 undergraduate Midwifery program students carried out the evaluation using a questionnaire on applicability, functionality, clarity, coherence and usability of the tool in Post-Partum Haemorrhage simulated stations. The data were analysed descriptively, considering absolute agreement when the answers to all questions in the five-point Likert scale corresponded to 5 (I totally agree). The Content Validity Index was calculated for the experts' questionnaires. RESULTS: In the validation stage, the experts agreed or totally agreed with all nine items, reaching a Content Validity Index = 1. In the total scores assigned by the experts, there was a variation between 80.0% and 100% absolute agreement, with a mean of 95.6%. In the students' assessment, the variation was between 87.5% and 100% absolute agreement, with a mean of 97.7%, in the eight items evaluated. The agreement level above 90% among experts and students was considered high. CONCLUSIONS: The Instructional Disk for the Management of Post-Partum Haemorrhage was validated by experts with extensive experience in Obstetrics and Midwifery care and teaching, ensuring that the content included in the guidelines for the management of Post-Partum Haemorrhage adopted in Brazil is covered. The students positively evaluated this support tool for learning the care to be provided in Post-Partum Haemorrhage cases in the simulated stations.

Efficacy and Safety of Direct Oral Anticoagulants for Stroke Prevention in Older Patients With Atrial Fibrillation: A Network Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Although older patients with atrial fibrillation are at heightened risk of thromboembolic and bleeding events, their optimal treatment choice remains uncertain. METHODS AND RESULTS: This meta-analysis was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We searched the PubMed, EMBASE, and Cochrane databases for randomized controlled trials that compared thromboembolic or bleeding outcomes between a direct oral anticoagulant (DOAC) and a vitamin K antagonist (VKA) and reported outcomes for patients aged ≥75 years with atrial fibrillation. The efficacy outcome was the composite of stroke and systemic embolism. Safety outcomes included major bleeding, any clinically relevant bleeding, and intracranial hemorrhage. Each DOAC and VKA was compared pairwise in a network meta-analysis. High- and low-dose regimens and factor IIa and Xa inhibitors were also compared. Seven randomized controlled trials were included in the analysis. Stroke and systemic embolism risks did not differ significantly among DOACs. There were no significant differences in major bleeding between each DOAC and VKA. Intracranial hemorrhage risk was significantly lower with dabigatran, apixaban, and edoxaban than with VKA and rivaroxaban, which had similar risks. High-dose regimens led to lower risks of stroke or systemic embolism compared with VKA and low-dose regimens, with both doses having similar bleeding risks. CONCLUSIONS: In patients aged ≥75 years with atrial fibrillation, DOACs were associated with fewer thromboembolic events compared with VKA, whereas dabigatran, apixaban, and edoxaban were associated with lower risks of intracranial hemorrhage compared with VKA and rivaroxaban. REGISTRATION: URL: www.crd.york.ac.uk/prospero/. Unique identifier: CRD42022329557.

Two Cases of Intractable Radiation-Induced Hemorrhagic Cystitis Treated with Transcatheter Embolization.

Radiation-induced hemorrhagic cystitis is a late complication of radiotherapy, and in rare cases, refractory. Refractory bleeding may not be resolved by transurethral electrocoagulation (TUEC) or hyperbaric oxygen (HBO) therapy and requires transcatheter arterial embolization (TAE) or urinary diversion. Here, we report two cases of radiation-induced hemorrhagic cystitis successfully treated with TAE. Case 1 was a 61-yearold man who underwent total prostatectomy for prostate cancer followed by salvage radiation therapy. The patient developed radiation-induced hemorrhagic cystitis 2 years and 3 months after radiotherapy. After no improvement with TUEC and HBO, TAE was performed. Case 2 was a 78-year-old man who underwent total prostatectomy followed by salvage radiation therapy and developed radiation-induced hemorrhagic cystitis 12 years later. TAE was performed after no improvement with HBO. TAE proved successful in both patients, and there was no relapse. TAE is a potential treatment option for refractory radiation-induced hemorrhagic cystitis.

Benefits and Harms of Standard Versus Reduced-Dose Direct Oral Anticoagulant Therapy for Older Adults With Multiple Morbidities and Atrial Fibrillation.

Background Dose reduction of direct oral anticoagulant (DOAC) medications is inconsistently applied to older adults with multiple morbidities, potentially due to perceived harms and unknown benefits of standard dosing. Methods and Results Using 2013 to 2017 US Medicare claims linked to Minimum Data Set records, we conducted a retrospective cohort study. We identified DOAC initiators (apixaban, dabigatran, rivaroxaban) aged ≥65 years with nonvalvular atrial fibrillation residing in a nursing home. We estimated inverse-probability of treatment weights for DOAC dose using propensity scores. We examined safety (hospitalization for major bleeding) and effectiveness outcomes (all-cause mortality, thrombosis [myocardial infarction, stroke, systemic embolism, venous thromboembolism]). We estimated hazard ratios (HRs) and 95% CIs using cause-specific hazard-regression models. Of 21 878 DOAC initiators, 48% received reduced dosing. The mean age of residents was 82.0 years, 66% were female, and 31% had moderate/severe cognitive impairment. After estimating inverse-probability of treatment weights, standard dosing was associated with a higher rate of bleeding (HR, 1.18 [95% CI, 1.03-1.37]; 9.4 versus 8.0 events per 100 person-years). Standard-dose therapy was associated with the highest rates of bleeding among those aged >80 years (9.1 versus 6.7 events per 100 person-years) and with a body mass index <30 kg/m2 (9.4 versus 7.4 events per 100 person-years). There was no association of dosing with mortality (HR, 0.99 [95% CI, 0.96-1.06]) or thrombotic events (HR, 1.16 [95% CI, 0.96-1.41]). Conclusions In this nationwide study of nursing home residents with nonvalvular atrial fibrillation, we found a higher rate of bleeding and little difference in effectiveness of standard versus reduced-dose DOAC treatment. Our results support the use of reduced-dose DOACs for many older adults with multiple morbidities.

Effect of Perioperative Tranexamic Acid on Blood Loss following Open Simple Prostatectomy: A Prospective Review in Nigerian Men.

BACKGROUND: Haemorrhage is a common complication following open simple prostatectomy and patients may sometimes require a blood transfusion. Tranexamic acid has been shown to reduce blood loss following transurethral resection of the prostate and open radical prostatectomy. This study evaluated the effect of perioperative intravenous administration of tranexamic acid on blood loss and blood transfusion rates in patients who had OSP for benign prostatic enlargement. METHODOLOGY: This was a comparative study of patients with documented prostate glands 60g and above scheduled for OSP. Initial hematocrit was done a day before surgery. The patients were randomized into a tranexamic acid group, which received perioperative intravenous tranexamic acid and the no-TXA group which received placebo (0.9% saline). All patients had open simple retropubic prostatectomy. Final post-operative hematocrit was assessed 72 hours after surgery, and blood loss was calculated using the modified Gross formula (actual blood loss = estimated blood volume x change in hematocrit / mean hematocrit). The transfusion rate was documented. RESULTS: Fifty-six patients participated in this study and were randomized into a tranexamic acid group and no-tranexamic acid group. The mean age of patients in the tranexamic acid group was 66.07 ±7.08 years and was comparable to the no- tranexamic acid group which was 66.50 ± 8.80 years (P = 0.842). The median total blood loss was lower in the tranexamic acid group (502mls, IQR 613) compared to the no-tranexamic acid group (801mls, IQR 1069). The difference in the median blood loss between the two groups was 299mls (U 275, P 0.055). The rate of blood transfusion was lower in the tranexamic acid group (6 patients, 21%) compared to the no tranexamic acid group (11 patients, 39%), (P = 0.146). There was no difference in complication rates between the two groups. CONCLUSION: The use of tranexamic acid in patients undergoing open simple prostatectomy showed a trend towards reduced intraoperative blood loss and less need no tranexamic for blood transfusion. This is of clinical significance, especially in elderly patients with low cardiovascular reserve.

CONTEXTE: L'hémorragie est une complication courante après une prostatectomie simple ouverte et les patients doivent parfois recevoir une transfusion sanguine. Il a été démontré que l'acide tranexamique réduit la perte de sang après une résection transurétrale de la prostate et une prostatectomie radicale ouverte. Cette étude a évalué l'effet de l'administration intraveineuse périopératoire d'acide tranexamique sur les pertes sanguines et les taux de transfusion sanguine chez des patients ayant subi une PSO pour hypertrophie bénigne de la prostate. MÉTHODOLOGIE: Il s'agissait d'une étude comparative de patients dont la prostate de 60 g et plus était documentée et qui devaient subir une PSO. L'hématocrite de base a été effectué un jour avant la chirurgie. Les patients ont été répartis aléatoirement dans le groupe acide tranexamique, qui a reçu de l'acide tranexamique periopératoire par voie intraveineuse, et dans le groupe sans TXA, qui a reçu un placebo. Tous les patients ont subi une prostatectomie rétropubienne simple ouverte. L'hématocrite postopératoire a été évalué, et la perte de sang calculée à l'aide de la formule de Gross modifiée. Le taux de transfusion a été documenté. RÉSULTATS: Cinquante-six patients ont participé à cette étude et ont été randomisés entre le groupe avec acide tranexamique et le groupe sans acide tranexamique. L'âge moyen des patients du groupe acide tranexamique était de 66,07 ±7,08 ans et était comparable à celui du groupe sans acide tranexamique qui était de 66,50 ± 8,80 ans (P =0,842). La perte sanguine totale médiane était plus faible dans le groupe avec acide tranexamique (502 ml, IQR 613) que dans le groupe sans acide tranexamique (801 ml, IQR 1069). La différence de la perte de sang médiane entre les deux groupes était de 299 ml (U 275, P 0,055). Le taux de transfusion sanguine était inférieur dans le groupe acide tranexamique (6 patients, 21%) par rapport au groupe sans acide tranexamique (11 patients, 39%), (P =0,146). Il n'y avait pas de différence dans les taux de complication entre les deux groupes. CONCLUSION: L'utilisation de l'acide tranexamique chez les patients subissant une prostatectomie simple ouverte a montré une tendance à la réduction de la perte de sang peropératoire et un besoin moindre de transfusion sanguine. Mots clés: Hypertrophie bénigne de la prostate, Prostatectomie simple ouverte, Hémorragie, Acide tranexamique.