Analisi di Fem coordinata da University College Cork
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Dieta mirata con psicobiotici riduce stress e ansia
Analisi di Fem coordinata da University College Cork
Abstract 104: Cytochrome B5 Reductase 3 Regulates The Erythropoietin Response To Ischemic Stroke In A Mouse Model Of Chronic Anemia And Oxidative Stress
Stroke, Volume 54, Issue Suppl_1, Page A104-A104, February 1, 2023. Introduction:Cytochrome b5 reductase 3 (Cyb5R3) is a heme iron reductase that reverses oxidized soluble guanylate cyclase (sGC) heme iron (Fe3+Fe2+) to preserve nitric oxide signaling. Under oxidative stress, such as occurs with sickle cell disease (SCD) and ischemic stroke, Cyb5R3 redox signaling provides resilience against tissue damage. A loss-of-function (roughly 50%) Cyb5R3 missense variant (T117S) occurs with high frequency (0.23 minor allele) in persons of African ancestry, who also suffer a greater burden of sickle cell anemia and ischemic stroke than other races. We hypothesized that Cyb5R3 regulates the erythropoietin response to ischemic stroke in a mouse model of SCD.Methods:Age-matched male SCD mice with wild-type Cyb5R3 (SSWT) or T117S Cyb5R3 (SST117S) underwent middle cerebral artery occlusion (55 min) and reperfusion (48 hr). Blood was sampled at baseline and 48h reperfusion for hematology measurements. Brains were stained with 2,3,5-triphenyltetrazolium chloride to quantify infarct volume. Erythropoietin (EPO), heme oxygenase 1 (HMOX1) and sGC were assayed by Western blot.Results:We found brain infarct volume to be greater in SST117Svs SSWT(63 vs 27 cm3, respectively; P=0.003). Red cells, hematocrit and hemoglobin decreased in SST117Spost-stroke, which was opposite to SSWT(red cells: -13% vs 13%, P=0.01; hematocrit: -20% vs 0%, P=0.03; hemoglobin: -18% vs 3%, P=0.02, respectively). In the absence of stroke (age-matched controls), SSWThad elevated HMOX1 protein compared to SST117S, which normalized in post-stroke SSWTbut was unchanged in post-stroke SST117S. Kidney and plasma EPO levels significantly increased in SSWTpost-stroke, but not in SST117S. In vitro studies using HEK293 cells showed EPO and HMOX1 decrease with Cyb5R3 knockdown by siRNA.Conclusion:Our findings suggest a modifying role for Cyb5R3 in brain-kidney crosstalk during ischemic stroke, wherein loss of T117S Cyb5R3 activity negatively impacts renal and plasma EPO levels and resilience against infarct of ischemic brain tissue. The Cyb5R3 axis on which the brain-kidney-blood response to stroke in SCD turns represents a novel target for precision medicine approaches to managing stroke risk and pathology in SCD carriers of the T117S variant.
Il ruolo della dieta nel trattamento delle malattie infiammatorie intestinali (MICI)
A woman case with chronic anemia, hypoalbuminemia, and ileo-ileal fistula
Dieta mediterranea protegge da rischio gestosi in gravidanza
Studio, verdure, legumi e pesce i cibi ‘amici’
Oxygen Delivery in the Treatment of Anemia
New England Journal of Medicine, Volume 387, Issue 25, Page 2362-2365, December 2022.
Practical Anemia Bundle for Sustained Blood Recovery (PABST-BR) in critical illness: a protocol for a randomised controlled trial
Introduction
Anaemia is highly prevalent in critical illness and is associated with impaired outcomes during and after hospitalisation. However, the impact of interventions designed to attenuate or treat anaemia during critical illness on post-hospitalisation haemoglobin recovery and functional outcomes is unclear.
Methods and analysis
The Practical Anemia Bundle for Sustained Blood Recovery (PABST-BR) clinical trial is a pragmatic, open-label, parallel group, single-centre, randomised clinical trial assessing the impact of a multifaceted anaemia prevention and treatment strategy versus standard care for improvement of haemoglobin concentrations and functional outcomes after critical illness. The intervention, which will be delivered early in critical illness for those with moderate-to-severe anaemia (ie, haemoglobin
Abstract 11358: Total Cost of Care in Heart Failure Patients Receiving Parenteral Iron Therapy for Iron Deficiency Anemia: A Retrospective Analysis
Circulation, Volume 146, Issue Suppl_1, Page A11358-A11358, November 8, 2022. Introduction:Iron deficiency (ID) is a common comorbidity in heart failure (HF) patients. This study compared healthcare costs between treatment with ferric carboxymaltose (FCM) and low dose IV iron (LDI) in HF patients with iron deficiency anemia (IDA).Methods:Medical and pharmacy claims from IQVIA PharMetrics®Plus data were analyzed. Adult patients who received FCM or LDI (i.e iron sucrose, iron dextran, sodium ferric gluconate complex in sucrose) from 2017 to 2019, who had HF and IDA medical claims and were continuously eligible 6 months before (baseline) and 12 months after first (index) IV iron infusion were included. Patients with chronic kidney disease who required dialysis were excluded. Eligible FCM patients were required to receive 2 FCM doses within 21 days of index date. Healthcare resource use and costs for pre- and post-index periods were summarized descriptively. Post-index monthly inpatient, outpatient (excluding IV iron), and total costs for FCM and LDI were compared using generalized linear model with gamma log-link adjusting for pre-index monthly cost, age, gender, year of index treatment and Charlson Comorbidity Index.Results:Data from 3,153 FCM patients and 3,971 LDI patients were analyzed. Unadjusted mean number of outpatient visits increased numerically in the LDI group and unchanged for FCM, whereas ER visits and inpatient admissions decreased numerically for both treatment groups in the post-index period compared to baseline. After adjusting for covariates, post-index monthly inpatient costs [adjusted cost ratio (ACR)= 0.70,p
Abstract 9537: Preliminary Analysis of the Impact of IV Iron Repletion in Patients With Iron Deficiency Anemia and Chronic Thromboembolic Pulmonary Hypertension Undergoing Pulmonary Thromboendarterectomy
Circulation, Volume 146, Issue Suppl_1, Page A9537-A9537, November 8, 2022. Introduction:Iron deficiency anemia (IDA) is associated with worse functional class, shorter 6-minute walk distance (6MWD), and higher mortality in heart failure. The associations of IDA with chronic thromboembolic pulmonary hypertension (CTEPH) have not been established.Methods:Retrospective chart review of 95 patients with CTEPH who underwent pulmonary thromboendarterectomy (PTE) and had iron studies. We determined the prevalence of IDA and the impact of IV iron repletion in the perioperative period.Results:Of the 95 patients, the mean age was 56 years, 55% were female, 52% were White, and 28% were Black. Thirteen (13.6%) had IDA and received IV iron perioperatively when admitted for PTE. Those who had IDA were younger (50.3 vs 57.7 years, p=0.09) and female (69.2%). Of the females, 3 (33.3%) had uterine fibroids. Baseline hemoglobin was lower in the group requiring IV iron (10.5 vs 13.1 g/dL, p=0.0004). The patients received 1-5 days of IV iron. Cardiac index (CI) pre-PTE was not different between IDA versus non-IDA groups (2.4 vs 2.2 L/min, p=0.35) and the PVR was non-statically different (8.4 vs. 7.2 WU, p=0.63). Post-PTE, CI were normal in both groups (2.4 vs 2.7 L/min, p=0.03). The IDA group had worse baseline NYHA functional class (75% class III or higher, p=0.66) than the non IDA group (90% class II or lower, p=0.66). Those with IDA had lower baseline 6MWD of 277 vs 343 meters (p=0.14; Fig 1), despite a similar baseline PVR and CI. Post PTE and after IV iron repletion, 6MWD were similar between the IDA and non IDA group 385 vs 348 meters; p=0.75, respectively.Conclusion:Our results suggest younger and female CTEPH patients may have a higher incidence of IDA. IDA contributes to the functional capacity of patients with precapillary CTEPH. There is a trend towards improvement of the functional impairment in the CTEPH patients when they receive IV iron repletion in the perioperative period of PTE, in groups that have similar baseline CI and PVR, and normal CI in the post-PTE period.
Abstract 13444: Acute Anemia With Mechanical Circulatory Support; Unmasking the Culprit
Circulation, Volume 146, Issue Suppl_1, Page A13444-A13444, November 8, 2022. Introduction:Mechanical circulatory support (MCS) is known to potentiate hemolytic anemia. Nevertheless, patients are also at an increased risk of spontaneous bleeding due to anticoagulation or post-procedural complication. We present two cases of acute anemia due to spontaneous retroperitoneal bleeding following insertion of the Impella assist device.Case Presentation:Two male patients aged 65 and 74 presented with cardiogenic shock secondary to ischemic cardiomyopathy with a low ejection fraction of 10% and 15%). Both patients initially had an intra-aortic balloon pump (IABP) inserted. Because of progressively deteriorating hemodynamics, IABP was switched to the Impella 5.5 device through the axillary artery. Following insertion of the Impella, they developed anemia requiring multiple blood transfusions. Despite repositioning of Impella, hemoglobin continued to drop prompting further workup. CT abdomen/pelvis revealed left retroperitoneal hematoma. CT angiogram showed active bleeding from the left L3 lumbar artery in one patient and multiple foci of active arterial extravasation in the other patient. Coil embolization was performed, achieving hemostasis and stabilization of hemoglobin levels in both patients.Discussion:Hemolytic anemia associated with the use of the Impella that improves with repositioning or device removal is well known and documented. However, patients with MCS are also at increased risk of spontaneous bleeding due to procedural injury and the use of anticoagulation. We report 2 cases with retroperitoneal bleeding from the lumbar artery diagnosed a few days after the placement of Impella. The occurrence of retroperitoneal hemorrhage was possibly spontaneous due to anticoagulation along with Impella-induced hemolysis resulting in acute anemia. Neither patient had any vascular access through the left groin making post-procedural complications less likely. The concealed nature and non-specific symptoms of retroperitoneal bleed can lead to a delay in diagnosis. Early identification and control of bleeding can prevent fatal outcomes.Conclusion:Our cases highlight the importance of clinicians having a broad differential and low threshold to investigate other causes of anemia in patients with MCS.
Abstract 15178: Impact of Anemia on Mortality Among Patients With Type 2 Myocardial Infarction
Circulation, Volume 146, Issue Suppl_1, Page A15178-A15178, November 8, 2022. Introduction:Anemia, a common precipitant of Type 2 Myocardial Infarction (T2MI), is well studied in Acute Coronary Syndrome (ACS), but its impact on mortality in T2MI population is lacking. We evaluated the association of hemoglobin (Hgb) levels on all-cause mortality within 60 days in patients with T2MI.Methods:In this single-center retrospective study, we evaluated 812 patients with Hgb > 7g/dl and troponin >0.04 ng/L ( >99thpercentile) presenting to a tertiary ED from 08/2016-08/2018. Exclusion criteria included patients with ischemic EKG changes, ACS treatment, cardiac catheterization showing intervenable lesions. Adjusted confounding variables are included in the figure. Iterative code was created to test each possible Hgb cut-off, from 7.1 to 15.2, to maximize the area under the curve while also looking for the smallest p-value and largest odds ratio. Five Hgb categories were then created, and mortality was calculated across groups. A multivariate-adjusted logistic regression model was used to predict mortality using Hgb category 13+ as the reference group.Results:Cut-off analysis showed Hgb of 9.9 as an inflection point of maximal mortality benefit (p 9.9.
Abstract 13962: Anemia Correction Improves Mortality and Other Outcomes in Patients With Incident Atrial Fibrillation: A Nationwide Cohort Study
Circulation, Volume 146, Issue Suppl_1, Page A13962-A13962, November 8, 2022. Background:Emerging evidence has suggested that anemia in patients with atrial fibrillation (AF) may lead to poor outcomes. We investigated the association of anemia after AF diagnosis with mortality and cardiovascular (CV) events.Methods:Using the database of Korean National Health Insurance Service and health examination, a total of 102,801 patients newly diagnosed with AF (2005-2015) were categorized into four groups according to the status of anemia before and after AF diagnosis. The primary outcomes were all-cause mortality and composite of CV death, ischemic stroke, heart failure hospitalization, or acute myocardial infarction.Results:The median follow-up duration was 5.3 years. Among AF patients with anticoagulation, the non-anemia to anemia and consistent anemia groups were associated with a higher risk of mortality (hazard ratio [95% CI]: 1.56 [1.34-1.80] and 1.59 [1.30-1.95]) and CV composite outcome (1.30 [1.15-1.47] and 1.28 [1.09-1.51]) compared to the consistent non-anemia group, respectively. Correction of anemia after diagnosis of AF (anemia to non-anemia group, HR [95%CI]: 1.38 [1.13-1.69]) showed a lower risk of mortality compared to the patients with persistent uncorrected anemia (consistent anemia group, 1.59 [1.30-1.95]). These results were consistently observed in AF patients without anticoagulation.Conclusions:Anemia was associated with an increased risk of mortality and CV outcomes in patients with newly diagnosed AF. Anemia correction after AF diagnosis could reduce the risk of subsequent CV events and mortality. Correction of anemia should be encouraged as part of a comprehensive approach to AF management to improve outcomes.
Abstract 15523: Breaking Bad – Severe Mechanical Hemolytic Anemia After Failed Mitral Valve Repair
Circulation, Volume 146, Issue Suppl_1, Page A15523-A15523, November 8, 2022. Introduction:Hemolytic anemia is a rare complication of mitral valve repair surgery. Mechanisms include a high-velocity regurgitant jet striking the annuloplasty ring or displacement of the annuloplasty ring with para-annular leak.Case Report:A 66 year old man with a past history of coronary artery disease was found to have severe, eccentric mitral regurgitation (MR) due to anterior mitral valve leaflet prolapse/flail at the A2 segment. At another institution, he underwent surgical mitral valve repair involving chordal transfer from P2 to A2 segment, suture closure of the resulting P2 defect, and ring annuloplasty. Intra-operative transesophageal echocardiography confirmed the elimination of MR. Three weeks later the patient presented with fatigue and cola-colored urine. Physical examination revealed a murmur of MR. Lab tests were consistent with severe hemolytic anemia, including hemoglobin of 6 g/dL, indirect hyperbilirubinemia, elevated lactate dehydrogenase, and a low haptoglobin level. Peripheral blood smear showed dysmorphic red blood cells suggestive of mechanical lysis. The patient required multiple transfusions of packed red blood cells. Acute kidney injury developed and was attributed to pigment nephropathy. He was transferred to our institution.Decision-making:Recurrent MR from failure of recent mitral valve repair was suspected. Transthoracic and transesophageal echocardiography confirmed severe eccentric MR. The Heart Team recommended re-operation. In the operating room, the suture repair of the P2 defect was found to have dehisced. Re-repair was deemed infeasible, and the mitral valve was replaced with a porcine bioprosthesis. Post-operatively, hemolysis resolved and renal function recovered.Conclusion:This case illustrates the importance of suspecting hemolysis from recurrent MR in patients presenting with unexplained anemia after mitral valve surgery. Re-operation is generally required to treat this rare condition.
Abstract 15411: Life After the Valve, Analyzing Post-Procedural Anemia and Mortality in Transcatheter Aortic Valve Replacement Patients
Circulation, Volume 146, Issue Suppl_1, Page A15411-A15411, November 8, 2022. Introduction:Transcatheter Aortic Valve Replacement (TAVR) has become the primary therapeutic option for many patients with severe aortic stenosis (AS). As a result, anemia is a prevalent co-morbidity amongst the TAVR population. Recent studies have demonstrated pre-procedural anemia is associated with increased long-term mortality in TAVR patients. However, the comparison of TAVR patients’ post-procedural anemia and its effect on mortality has not been fully investigated.Methods:Retrospective analysis of electronic medical records from 2018-2021 at the University of Illinois at Chicago and Jesse Brown VA Medical Center identified TAVR patients. Primary outcomes included all-cause mortality and significant bleeding at 6-months and 12-months post-TAVR.Results:We included 160 patients in the analysis. They were 122 males, 56.88% non-white, and an average age of 73.88. At 6-months, patients who experienced all-cause mortality had an average hemoglobin of 9.85 (g/dL) compared to an average hemoglobin of 11.31 in those patients that survived (p = 0.020). There was no significant difference in major bleeding events between the two groups (p = 0.974) as well as no significant difference in past-medical history, including hypertension, hyperlipidemia (HLD), diabetes mellitus, history of stroke and history of myocardial infarction. At 12-months, patients who experienced all-cause mortality had an average hemoglobin of 10.18 compared to an average hemoglobin of 11.36 in those patients that survived (p = 0.014). There was no significant difference in major bleeding events (p = 0.753) and no significant difference in past-medical history, except for hyperlipidemia. The prevalence of HLD was 59.09% in those that experienced all-cause mortality compared to 78.72% in those that did not (p = 0.045).Conclusions:Our results suggest that patients with lower hemoglobin levels after TAVR are at a greater risk of all-cause mortality compared to those with higher hemoglobin levels. These patients may benefit from closer follow-up after the procedure.
Abstract 10855: Murine Model of Phenylhydrazine-Induced Chronic Hemolytic Anemia Leads to Development of Early Pulmonary Hypertension
Circulation, Volume 146, Issue Suppl_1, Page A10855-A10855, November 8, 2022. Introduction:Pulmonary hypertension (PH) in sickle cell disease is associated with high morbidity and early mortality, yet the pathogenesis remains incompletely understood.In vitrodata by our group implicates extracellular hemoglobin in the endothelial dysfunction that leads to precapillary vascular changes seen in PH and identifies endothelial to mesenchymal transition (EndoMT) as a likely mechanism. To support these findings, we hypothesize that a murine model of chronic hemolysis will show signs of EndoMT and early development of PH.MethodsC57BL/6J mice were treated with 40 mg/kg of phenylhydrazine (PHZ), a toxin known to induce hemolysis, or saline, as control, twice a week for three weeks. Plasma cytokine concentrations and complete blood counts were measured. Non-invasive and invasive measures of PH were obtained by echocardiography (TTE), hemodynamic pressure assessments, and measures of right ventricular (RV) hypertrophy. Explanted lung tissue was homogenized and subjected to Western blot analysis to evaluate markers of EndoMT.ResultsPHZ administration causes anemia (9.1 g/dL vs 11.4 g/dL in control mice) without a significant drop in other hematopoietic cell lines. PHZ-treated mice have increased plasma cytokines CXCL1 and IL-6, which are known to be upregulated in PH. TTE shows significantly decreased pulmonary artery acceleration time (16.7 vs 19.5 msec, p < 0.05), and a trend toward decreased tricuspid annular plane systolic excursion in PHZ-treated mice (0.9 vs 1.2 mm). Invasive hemodynamics show a slight increase in right ventricular systolic pressure (25.6 vs 23.4 mm Hg) and analysis of RV hypertrophy shows increased Fulton index in PHZ-treated mice compared to control (0.28 vs 0.24). Western blot analysis of lung tissue shows upregulation of EndoMT transcription factor SNAI2 in PHZ-treated mice versus control.ConclusionsPHZ-treated mice demonstrate early invasive and non-invasive signs of PH with upregulation of EndoMT transcription factor SNAI2, suggesting a relationship between hemolysis, EndoMT, and the development of PH. PHZ administration may be a novel murine model for PH due to chronic hemolysis, facilitating pathobiological and therapeutic discovery for this devastating complication of sickle cell disease.