Resilient anatomy and local plasticity of naive and stress haematopoiesis.

The bone marrow adjusts blood cell production to meet physiological demands in response to insults. The spatial organization of normal and stress responses are unknown owing to the lack of methods to visualize most steps of blood production. Here we develop strategies to image multipotent haematopoiesis, erythropoiesis and lymphopoiesis in mice. We combine these with imaging of myelopoiesis1 to define the anatomy of normal and stress haematopoiesis. In the steady state, across the skeleton, single stem cells and multipotent progenitors distribute through the marrow enriched near megakaryocytes. Lineage-committed progenitors are recruited to blood vessels, where they contribute to lineage-specific microanatomical structures composed of progenitors and immature cells, which function as the production sites for each major blood lineage. This overall anatomy is resilient to insults, as it was maintained after haemorrhage, systemic bacterial infection and granulocyte colony-stimulating factor (G-CSF) treatment, and during ageing. Production sites enable haematopoietic plasticity as they differentially and selectively modulate their numbers and output in response to insults. We found that stress responses are variable across the skeleton: the tibia and the sternum respond in opposite ways to G-CSF, and the skull does not increase erythropoiesis after haemorrhage. Our studies enable in situ analyses of haematopoiesis, define the anatomy of normal and stress responses, identify discrete microanatomical production sites that confer plasticity to haematopoiesis, and uncover unprecedented heterogeneity of stress responses across the skeleton.

Sex Differences in Sympathetic Responses to Lower-Body Negative Pressure.

INTRODUCTION: Trauma-induced hemorrhage is a leading cause of death in prehospital settings. Experimental data demonstrate that females have a lower tolerance to simulated hemorrhage (i.e., central hypovolemia). However, the mechanism(s) underpinning these responses are unknown. Therefore, this study aimed to compare autonomic cardiovascular responses during central hypovolemia between the sexes. We hypothesized that females would have a lower tolerance and smaller increase in muscle sympathetic nerve activity (MSNA) to simulated hemorrhage. METHODS: Data from 17 females and 19 males, aged 19-45 yr, were retrospectively analyzed. Participants completed a progressive lower-body negative pressure (LBNP) protocol to presyncope to simulate hemorrhagic tolerance with continuous measures of MSNA and beat-to-beat hemodynamic variables. We compared responses at baseline, at two LBNP stages (-40 and -50 mmHg), and at immediately before presyncope. In addition, we compared responses at relative percentages (33%, 66%, and 100%) of hemorrhagic tolerance, calculated via the cumulative stress index (i.e., the sum of the product of time and pressure at each LBNP stage). RESULTS: Females had lower tolerance to central hypovolemia (female: 561 ± 309 vs male: 894 ± 304 min·mmHg [time·LBNP]; P = 0.003). At LBNP -40 and -50 mmHg, females had lower diastolic blood pressures (main effect of sex: P = 0.010). For the relative LBNP analysis, females exhibited lower MSNA burst frequency (main effect of sex: P = 0.016) accompanied by a lower total vascular conductance (sex: P = 0.028; main effect of sex). CONCLUSIONS: Females have a lower tolerance to central hypovolemia, which was accompanied by lower diastolic blood pressure at -40 and -50 mmHg LBNP. Notably, females had attenuated MSNA responses when assessed as relative LBNP tolerance time.

Effect of Therapeutically Related Drugs on Coagulation-Anticoagulation Balance in Acute Promyelocytic Leukemia.

Acute promyelocytic leukemia (APL) usually presents with a series of coagulation-anticoagulation disturbance. Early administration of All-trans retinoic acid (ATRA) can reduce the risk of bleeding, but the potential for thrombosis needs to be addressed in some cases. The role of arsenic agent in correcting coagulation disorder remains to be studied, but oral arsenic agent shows potential advantages in coagulation recovery compared with intravenous agent, and chemotherapy can aggravate the progress of coagulation disease. In addition to early application of ATRA, avoiding invasive procedures and transfusion support can reduce the risk of bleeding. Whether the administration of heparin, thrombomodulin, recombinant factor VIIa or antifibrinolytics reduces the risk of bleeding and thrombosis associated with APL remains to be further explored, and their routine use outside of clinical trials is not recommended. This article reviews the effects of related drugs on coagulation-anticoagulation balance in APL patients.

Choice of antithrombotic therapy for patients with atrial fibrillation undergoing carotid angioplasty and stenting: a nationwide population-based study.

Nonvalvular atrial fibrillation (NVAF) and carotid stenosis are important risk factors for stroke. Carotid angioplasty and stent placement (CAS) is recommended for patients with symptomatic high-grade carotid stenosis. The optimal medical management for patients with NVAF after CAS remains unclear. We aimed to clarify this issue using real-world data from the Taiwanese National Health Insurance Research Database (NHIRD). In total, 2116 consecutive NVAF patients who received CAS between January 1, 2010, and December 31, 2016, from NHIRD were divided into groups based on post-procedure medication as follows: only antiplatelet agent (OAP, n = 587); only anticoagulation agent (OAC, n = 477); dual antiplatelet agents (DAP, n = 49); and a combination of antiplatelet and anticoagulation agents (CAPAC, n = 304). Mortality, vascular events, and major bleeding episodes were compared after matching with the Charlson comorbidity index and CHA2DS2-VASc score. The CAPAC and the OAC groups had lower mortality rates than the OAP group (P = 0.0219), with no statistical differences in major bleeding, ischemic stroke, or vascular events. Conclusively, OAC therapy after CAS appears suitable for NVAF patients. CAPAC therapy might be considered as initial therapy or when there is concern about vascular events.

ADP-induced platelet reactivity and bleeding events in patients with acute myocardial infarction complicated by cardiogenic shock.

While previous reports showed ADP-induced platelet reactivity to be an independent predictor of bleeding after PCI in stable patients, this has never been investigated in patients with cardiogenic shock. The association of bleeding events with respect to ADP-induced platelet aggregation was investigated in patients undergoing primary PCI for acute myocardial infarction complicated by cardiogenic shock and with available on-treatment ADP-induced platelet aggregation measurements. Out of 233 patients, 74 suffered from a severe BARC3 or higher bleed. ADP-induced platelet aggregation was significantly lower in patients with BARC≥3 bleedings (p < .001). Multivariate analysis identified on-treatment ADP-induced platelet aggregation as an independent risk factor for bleeding (HR = 0.968 per AU). An optimal cutoff value of <12 AU for ADP-induced platelet aggregation to predict BARC≥3 bleedings was identified via ROC analysis. Moreover, the use of VA-ECMO (HR 1.972) or coaxial left ventricular pump (HR 2.593), first lactate (HR 1.093 per mmol/l) and thrombocyte count (HR 0.994 per G/l) were independent predictors of BARC≥3 bleedings. In conclusion, lower on-treatment ADP-induced platelet aggregation was independently associated with severe bleeding events in patients with AMI-CS. The value of platelet function testing for bleeding risk prediction and guidance of anti-thrombotic treatment in cardiogenic shock warrants further investigation.

Renal Denervation in Combination With Angiotensin Receptor Blockade Prolongs Blood Pressure Trough During Hemorrhage.

Majority of patients with hypertension and chronic kidney disease (CKD) undergoing renal denervation (RDN) are maintained on antihypertensive medication. However, RDN may impair compensatory responses to hypotension induced by blood loss. Therefore, continuation of antihypertensive medications in denervated patients may exacerbate hypotensive episodes. This study examined whether antihypertensive medication compromised hemodynamic responses to blood loss in normotensive (control) sheep and in sheep with hypertensive CKD at 30 months after RDN (control-RDN, CKD-RDN) or sham (control-intact, CKD-intact) procedure. CKD-RDN sheep had lower basal blood pressure (BP; ≈9 mm Hg) and higher basal renal blood flow (≈38%) than CKD-intact. Candesartan lowered BP and increased renal blood flow in all groups. 10% loss of blood volume alone caused a modest fall in BP (≈6-8 mm Hg) in all groups but did not affect the recovery of BP. 10% loss of blood volume in the presence of candesartan prolonged the time at trough BP by 9 minutes and attenuated the fall in renal blood flow in the CKD-RDN group compared with CKD-intact. Candesartan in combination with RDN prolonged trough BP and attenuated renal hemodynamic responses to blood loss. To minimize the risk of hypotension-mediated organ damage, patients with RDN maintained on antihypertensive medications may require closer monitoring when undergoing surgery or experiencing traumatic blood loss.

Low-dose fentanyl does not alter muscle sympathetic nerve activity, blood pressure, or tolerance during progressive central hypovolemia.

Hemorrhage is a leading cause of battlefield and civilian trauma deaths. Several pain medications, including fentanyl, are recommended for use in the prehospital (i.e., field setting) for a hemorrhaging solider. However, it is unknown whether fentanyl impairs arterial blood pressure (BP) regulation, which would compromise hemorrhagic tolerance. Thus, the purpose of this study was to test the hypothesis that an analgesic dose of fentanyl impairs hemorrhagic tolerance in conscious humans. Twenty-eight volunteers (13 females) participated in this double-blinded, randomized, placebo-controlled trial. We conducted a presyncopal limited progressive lower body negative pressure test (LBNP; a validated model to simulate hemorrhage) following intravenous administration of fentanyl (75 µg) or placebo (saline). We quantified tolerance as a cumulative stress index (mmHg·min), which was compared between trials using a paired, two-tailed t test. We also compared muscle sympathetic nerve activity (MSNA; microneurography) and beat-to-beat BP (photoplethysmography) during the LBNP test using a mixed effects model [time (LBNP stage) × trial]. LBNP tolerance was not different between trials (fentanyl: 647 ± 386 vs. placebo: 676 ± 295 mmHg·min, P = 0.61, Cohen's d = 0.08). Increases in MSNA burst frequency (time: P < 0.01, trial: P = 0.29, interaction: P = 0.94) and reductions in mean BP (time: P < 0.01, trial: P = 0.50, interaction: P = 0.16) during LBNP were not different between trials. These data, the first to be obtained in conscious humans, demonstrate that administration of an analgesic dose of fentanyl does not alter MSNA or BP during profound central hypovolemia, nor does it impair tolerance to this simulated hemorrhagic insult.

Thrombotic and Hemorrhagic Incidences in Patients After Discharge from COVID-19 Infection: A Systematic Review and Meta-Analysis.

BACKGROUND: The association between coronavirus infection 2019 (COVID-19) and thrombosis has been explicitly shown through numerous reports that demonstrate high rates of thrombotic complications in infected patients. Recently, much evidence has shown that patients who survived COVID-19 might have a high thrombotic risk after hospital discharge. This current systematic review and meta-analysis was conducted to better understand the incidence of thrombosis, bleeding, and mortality rates among patients discharged after COVID-19 hospitalization. METHODS: Using a search strategy that included terms for postdischarge, thrombosis, and COVID-19, 2 investigators independently searched for published articles indexed in the MEDLINE, Embase, and Scopus databases that were published before August 2021. Pooled incidences and 95% confidence intervals were calculated using the DerSimonian-Laird random-effects model with a double arcsine transformation. RESULTS: Twenty articles were included in the meta-analysis. They provided a total of 19 461 patients discharged after COVID-19 hospitalization. The weighted pooled incidence of overall thrombosis among the patients was 1.3% (95 CI, 0. 6-2; I2 90.5), with a pooled incidence of venous thrombosis of 0.7% (95 CI, 0. 4-1; I2 73.9) and a pooled incidence of arterial thrombosis of 0.6% (95 CI, 0. 2-1; I2 88.1). The weighted pooled incidences of bleeding and mortality were 0.9% (95 CI, 0. 1-1.9; I2 95.1) and 2.8% (95 CI, 0. 6-5; I2 98.2), respectively. CONCLUSIONS: The incidences of thrombosis and bleeding in patients discharged after COVID-19 hospitalization are comparable to those of medically ill patients.

Rebalanced hemostasis in liver disease: a misunderstood coagulopathy.

The combination of frequently abnormal hemostatic markers and catastrophic bleeding as seen with variceal hemorrhage has contributed to the longstanding misperception that chronic liver disease (CLD) constitutes a bleeding diathesis. Laboratory studies of hemostasis in liver disease consistently challenge this with global coagulation assays incorporating activation of the protein C pathway demonstrating rebalanced hemostasis. It is now recognized that bleeding in CLD is predominantly secondary to portal hypertension (rather than a coagulopathy) and additionally that these patients are at increased risk of venous thrombosis, particularly in the portal venous system. This narrative review describes the current understanding of hemostasis in liver disease, as well as the periprocedural management of hemostasis and anticoagulation for management of venous thromboembolism in patients with CLD.

Quantification of stroke volume in a simulated healthy volunteer model of traumatic haemorrhage; a comparison of two non-invasive monitoring devices using error grid analysis alongside traditional measures of agreement.

INTRODUCTION: Haemorrhage is a leading cause of death following traumatic injury and the early detection of hypovolaemia is critical to effective management. However, accurate assessment of circulating blood volume is challenging when using traditional vital signs such as blood pressure. We conducted a study to compare the stroke volume (SV) recorded using two devices, trans-thoracic electrical bioimpedance (TEB) and supra-sternal Doppler (SSD), against a reference standard using trans- thoracic echocardiography (TTE). METHODS: A lower body negative pressure (LBNP) model was used to simulate hypovolaemia and in half of the study sessions lower limb tourniquets were applied as these are common in military practice and can potentially affect some haemodynamic monitoring systems. In order to provide a clinically relevant comparison we constructed an error grid alongside more traditional measures of agreement. RESULTS: 21 healthy volunteers aged 18-40 were enrolled and underwent 2 sessions of LBNP, with and without lower limb tourniquets. With respect to absolute SV values Bland Altman analysis showed significant bias in both non-tourniquet and tourniquet strands for TEB (-42.5 / -49.6 ml), rendering further analysis impossible. For SSD bias was minimal but percentage error was unacceptably high (35% / 48%). Degree of agreement for dynamic change in SV, assessed using 4 quadrant plots showed a seemingly acceptable concordance rate for both TEB (86% / 93%) and SSD (90% / 91%). However, when results were plotted on an error grid, constructed based on expert clinical opinion, a significant minority of measurement errors were identified that had potential to lead to moderate or severe patient harm. CONCLUSION: Thoracic bioimpedance and suprasternal Doppler both demonstrated measurement errors that had the potential to lead to clinical harm and caution should be applied in interpreting the results in the detection of early hypovolaemia following traumatic injury.

Blood pressure changes during the first 24 hours of life and the association with the persistence of a patent ductus arteriosus and occurrence of intraventricular haemorrhage.

Very low birthweight (VLBW) infants are at risk of intraventricular haemorrhage (IVH) and delayed closure of ductus arteriosus. We investigated mean arterially recorded blood pressure (MAP) changes during the first day of life in VLBW infants as potential risk factors for a patent ductus arteriosus (PDA) and IVH. This retrospective cohort study exploring MAP changes during adaption and risk factors for a PDA and IVH comprised 844 VLBW infants admitted to the Helsinki University Children's Hospital during 2005-2013. For each infant, we investigated 600 time-points of MAP recorded 4-24 hours after birth. Based on blood pressure patterns revealed by a data-driven method, we divided the infants into two groups. Group 1 (n = 327, mean birthweight = 1019 g, mean gestational age = 28 + 1/7 weeks) consisted of infants whose mean MAP was lower at 18-24 hours than at 4-10 hours after birth. Group 2 (n = 517, mean birthweight = 1070 g, mean gestational age = 28 + 5/7 weeks) included infants with a higher mean MAP at 18-24 hours than at 4-10 hours after birth. We used the group assignments, MAP, gestational age at birth, relative size for gestational age, surfactant administration, inotrope usage, invasive ventilation, presence of respiratory distress syndrome or sepsis, fluid intake, and administration of antenatal steroids to predict the occurrence of IVH and use of pharmacological or surgical therapy for a PDA before 42 weeks of gestational age. Infants whose mean MAP is lower at 18-24 hours than at 4-10 hours after birth are more likely to undergo surgical ligation of a PDA (odds ratio = 2.1; CI 1.14-3.89; p = 0.018) and to suffer from IVH (odds ratio = 1.83; CI 1.23-2.72; p = 0.003).

Predictors of hemorrhagic complications after intravenous thrombolysis in acute cerebral infarction patients: A single-center study of 391 cases.

ABSTRACT: For patients with ischemic stroke, intravenous (IV) thrombolysis with Urokinase within 6 hours has been accepted as beneficial, but its application is limited by high risk of hemorrhagic complications after thrombolysis. This study aimed to analyze the risk factors of hemorrhagic complications after intravenous thrombolysis using Urokinase in acute cerebral infarction (ACI) patients.Total 391 consecutive ACI patients were enrolled and divided into 2 groups: the hemorrhagic complications group and the non-hemorrhagic complications group. The related data were collected and analyzed.Univariate analysis showed significant differences in prothrombin time, atrial fibrillation (AF), Mean platelet volume, large platelet ratio (L-PLR), triglyceride (TG), Lactate dehydrogenase, alanine aminotransferase (ALT), high-density lipoprotein, and baseline National Institute of Health Stroke Scale score between the hemorrhagic complications and the non-hemorrhagic complications group (P < .1). Multivariate logistic regression analysis indicated that AF (odds ratio [OR] = 2.91, 95% confidence interval [CI] = 1.06-7.99 P = .039) was the risk factor of hemorrhagic complications, while ALT (OR = 0.27, 95% CI = 0.10-0.72 P = .009) and TG (OR = 0.16, 95% CI = 0.06-0.45 P = .000) were protective factors of hemorrhagic complications.For patients with AF and lower levels of ALT or TG, the risk of hemorrhagic complications might increase after ACI.

[Step by step - A diagnostic approach to bleeding disorders]. / Abklärung erhöhter Blutungsneigung ­ Schritt für Schritt.

The main symptom of hemorrhagic diathesis is an increased bleeding tendency. Due to the subjectivity of various features of the bleeding history, unclarity of the family history, and an individualization of the extent of diagnostic the evaluation of a suspected bleeding disorder represents a challenging endeavour in hematology. Hemorrhagic diathesis can be divided into the following sub-categories: disorders in primary hemostasis (e. g. von Willebrand disease, different causes of thrombocytopenia), secondary hemostasis (e. g. hemophilia A and B, Vitamin K deficiency) and fibrinolysis, and in connective tissue or vascular formation. This article reviews available diagnostic methods for bleeding disorders, from structured patient history to highly specialized laboratory diagnosis.

Bleeding and Thrombosis: Insights into Pathophysiology of Bothrops Venom-Related Hemostasis Disorders.

Toxins from Bothrops venoms targeting hemostasis are responsible for a broad range of clinical and biological syndromes including local and systemic bleeding, incoagulability, thrombotic microangiopathy and macrothrombosis. Beyond hemostais disorders, toxins are also involved in the pathogenesis of edema and in most complications such as hypovolemia, cardiovascular collapse, acute kidney injury, myonecrosis, compartmental syndrome and superinfection. These toxins can be classified as enzymatic proteins (snake venom metalloproteinases, snake venom serine proteases, phospholipases A2 and L-amino acid oxidases) and non-enzymatic proteins (desintegrins and C-type lectin proteins). Bleeding is due to a multifocal toxicity targeting vessels, platelets and coagulation factors. Vessel damage due to the degradation of basement membrane and the subsequent disruption of endothelial cell integrity under hydrostatic pressure and tangential shear stress is primarily responsible for bleeding. Hemorrhage is promoted by thrombocytopenia, platelet hypoaggregation, consumption coagulopathy and fibrin(ogen)olysis. Onset of thrombotic microangiopathy is probably due to the switch of endothelium to a prothrombotic phenotype with overexpression of tissue factor and other pro-aggregating biomarkers in association with activation of platelets and coagulation. Thrombosis involving large-caliber vessels in B. lanceolatus envenomation remains a unique entity, which exact pathophysiology remains poorly understood.

Hemostasis using re-radiofrequency ablation for hepatic tract bleeding after ultrasound-guided percutaneous radiofrequency ablation of hepatic tumors.

OBJECTIVE: To evaluate the hemostatic efficacy of re-radiofrequency ablation (re-RFA) for hepatic tract bleeding after ultrasound-guided RFA of hepatic tumors. METHODS: A total of 4679 percutaneous ultrasound-guided RFA procedures were performed for hepatic tumors at Samsung Medical Center between January 2012 and December 2020. We identified patients who had hepatic tract bleeding after RFA by reviewing radiologic reports and ultrasound images and investigated the measures taken to control the bleeding and their outcomes. We also identified patients who had a significant peritoneal hematoma on immediate post-RFA CT or underwent transarterial embolization to control hepatic bleeding after RFA of hepatic tumors. RESULTS: In total, 91 patients with tract bleeding after RFA were identified. As initial measures to control the bleeding, external compression, re-RFA, and observation were performed in 71 (78%), 17 (19%), and 3 (3%) patients, respectively. Hemostasis using re-RFA was attempted to control tract bleeding in 40 patients as an initial measure or an additional measure after other initial efforts. In all 40 patients, the bleeding stopped after re-RFA on Doppler ultrasound, and there was no active bleeding on the immediate follow-up CT. During the study period, in the years when re-RFA was performed frequently, the number of transarterial embolizations to control tract bleeding and significant peritoneal hematoma formation tended to be low. CONCLUSION: Hemostasis using re-RFA of the needle tract is effective in controlling tract bleeding after ultrasound-guided RFA of hepatic tumors. ADVANCES IN KNOWLEDGE: Re-RFA is a simple, safe, and effective method to control tract bleeding.

Reversing Rivaroxaban Anticoagulation as Part of a Multimodal Hemostatic Intervention in a Polytrauma Animal Model.

BACKGROUND: Life-threatening bleeding requires prompt reversal of the anticoagulant effects of factor Xa inhibitors. This study investigated the effectiveness of four-factor prothrombin complex concentrate in treating trauma-related hemorrhage with rivaroxaban-anticoagulation in a pig polytrauma model. This study also tested the hypothesis that the combined use of a low dose of prothrombin complex concentrate plus tranexamic acid and fibrinogen concentrate could improve its subtherapeutic effects. METHODS: Trauma (blunt liver injury and bilateral femur fractures) was induced in 48 anesthetized male pigs after 30 min of rivaroxaban infusion (1 mg/kg). Animals in the first part of the study received prothrombin complex concentrate (12.5, 25, and 50 U/kg). In the second part, animals were treated with 12.5 U/kg prothrombin complex concentrate plus tranexamic acid or plus tranexamic acid and fibrinogen concentrate. The primary endpoint was total blood loss postinjury. The secondary endpoints (panel of coagulation parameters and thrombin generation) were monitored for 240 min posttrauma or until death. RESULTS: The first part of the study showed that blood loss was significantly lower in the 25 U/kg prothrombin complex concentrate (1,541 ± 269 ml) and 50 U/kg prothrombin complex concentrate (1,464 ± 108 ml) compared with control (3,313 ± 634 ml), and 12.5 U/kg prothrombin complex concentrate (2,671 ± 334 ml, all P < 0.0001). In the second part of the study, blood loss was significantly less in the 12.5 U/kg prothrombin complex concentrate plus tranexamic acid and fibrinogen concentrate (1,836 ± 556 ml, P < 0.001) compared with 12.5 U/kg prothrombin complex concentrate plus tranexamic acid (2,910 ± 856 ml), and there were no early deaths in the 25 U/kg prothrombin complex concentrate, 50 U/kg prothrombin complex concentrate, and 12.5 U/kg prothrombin complex concentrate plus tranexamic acid and fibrinogen concentrate groups. Histopathologic analyses postmortem showed no adverse events. CONCLUSIONS: Prothrombin complex concentrate effectively reduced blood loss, restored hemostasis, and balanced thrombin generation. A multimodal hemostatic approach using tranexamic acid plus fibrinogen concentrate enhanced the effect of low doses of prothrombin complex concentrate, potentially reducing the prothrombin complex concentrate doses required for effective bleeding control.

Another controller system for arterial pressure. AngII-vasopressin neural network of the parvocellular paraventricular nucleus may regulate arterial pressure during hypotension.

Angiotensin II (AngII) immunoreactive cells, fibers and receptors, were found in the parvocelluar region of paraventricular nucleus (PVNp) and AngII receptors are present on vasopressinergic neurons. However, the mechanism by which vasopressin (AVP) and AngII may interact to regulate arterial pressure is not known. Thus, we tested the cardiovascular effects of blockade of the AngII receptors on AVP neurons and blockade of vasopressin V1a receptors on AngII neurons. We also explored whether the PVNp vasopressin plays a regulatory role during hypotension in anesthetized rat or not. Hypovolemic-hypotension was induced by gradual bleeding from femoral venous catheter. Either AngII or AVP injected into the PVNp produced pressor and tachycardia responses. The responses to AngII were blocked by V1a receptor antagonist. The responses to AVP were partially attenuated by AT1 antagonist and greatly attenuated by AT2 antagonist. Hemorrhage augmented the pressor response to AVP, indicating that during hemorrhage, sensitivity of PVNp to vasopressin was increased. By hemorrhagic-hypotension and bilateral blockade of V1a receptors of the PVNp, we found that vasopressinergic neurons of the PVNp regulate arterial pressure towards normal during hypotension. Taken together these findings and our previous findings about angII (Khanmoradi and Nasimi, 2017a) for the first time, we found that a mutual cooperative system of angiotensinergic and vasopressinergic neurons in the PVNp is a major regulatory controller of the cardiovascular system during hypotension.

Length of stay following percutaneous left atrial appendage occlusion: Data from the prospective, multicenter Amplatzer Amulet Occluder Observational Study.

AIMS: To evaluate factors influencing the length of stay in patients undergoing percutaneous left atrial appendage occlusion (LAAO). METHODS AND RESULTS: Patient characteristics, procedural data and the occurrence of serious adverse events were analyzed from the AmplatzerTM AmuletTM Occluder Observational Study. Patients were divided into three groups: same day (S, 0day, n = 60, 5.6%) early (E, 1day, n = 526, 48.9%), regular (R, 2-3days, n = 338, 31.4%) and late (L, ≥4days, n = 152, 14.1%) discharge and followed up for 60 days. Procedure and device related SAE during the in-hospital stay (S: 0.0% vs. E: 1.0% vs. R: 2.1% vs. L: 23%, p<0.0001) were a major trigger for a prolonged in-hospital stay. Of the 37 subjects in the late discharge group with an SAE prior to discharge, cardiac or bleeding complications were the most common underlying conditions, occurring in 26 subjects. Multinomial logistic analysis only identified HAS-BLED score as an independent influencing factor (p = 0.04) for a late discharge. After 60 days, mortality tended to be greatest in the late discharge group (S: 0.0% vs. E: 1.0% vs. R: 1.2% vs. L: 3.3%, p = 0.1066). CONCLUSION: Over half of the subjects receiving an Amplatzer Amulet occluder were discharged within 1 day of the implant procedure. Serious adverse events were a major trigger for a late discharge after LAAO. Increased HAS-BLED score was associated with a prolonged in-hospital stay.

Adrenal hemorrhage and hemorrhagic masses; diagnostic workup and imaging findings.

Adrenal hemorrhage (AH) is a rare condition. It can be traumatic or non-traumatic. Most common causes are septicemia, coagulopathy or bleeding diathesis, and underlying neoplasms. Other reported less common causes of AH are COVID-19 and neonatal stress. Clinical diagnosis of AH is challenging due to its non-specific presentation and occurrence in the setting of acute medical illness. Therefore, most cases are diagnosed incidentally on imaging. Having high clinical suspicion in the proper clinical setting for AH is crucial to avoid life-threatening adrenal insufficiency that occurs in 16-50% of patients with bilateral AH. We discuss the clinical situations that predispose to AH, review the imaging features on different imaging modalities, highlight a variety of clinical cases, imaging features that should be concerning for an underlying neoplasm, and outline the potential role of interventional radiology in management of AH.

Compensatory reserve detects subclinical shock with more expeditious prediction for need of life-saving interventions compared to systolic blood pressure and blood lactate.

INTRODUCTION: We conducted a prospective observational study on 205 trauma patients at a level I trauma facility to test the hypothesis that a compensatory reserve measurement (CRM) would identify higher risk for progression to shock and/or need a life-saving interventions (LSIs) earlier than systolic blood pressure (SBP) and blood lactate (LAC). METHODS: A composite outcome metric included blood transfusion, procedural LSI, and mortality. Discrete measures assessed as abnormal (ab) were SBP <90 mmHg, CRM <60%, and LAC >2.0. A graded categorization of shock was defined as: no shock (normal [n] SBP [n-SBP], n-CRM, n-LAC); sub-clinical shock (ab-CRM, n-SBP, n-LAC); occult shock (n-SBP, ab-CRM, ab-LAC); or overt shock (ab-SBP, ab-CRM, ab-LAC). RESULTS: Three patients displayed overt shock, 53 displayed sub-clinical shock, and 149 displayed no shock. After incorporating lactate into the analysis, 86 patients demonstrated no shock, 25 were classified as sub-clinical shock, 91 were classified as occult shock, and 3 were characterized as overt shock. Each shock subcategory revealed a graded increase requiring LSI and transfusion. Initial CRM was associated with progression to shock (odds ratio = 0.97; p < .001) at an earlier time than SBP or LAC. CONCLUSIONS: Initial CRM uncovers a clinically relevant subset of patients who are not detected by SBP and LAC. Our results suggest CRM could be used to more expeditiously identify injured patients likely to deteriorate to shock, with requirements for blood transfusion or procedural LSI.