Circulatory Dysfunction Research Articles

Terapia médico-nutricional en pacientes politraumatizados: una carrera contra el tiempo.

A polytraumatized patient is defined as one who has multiple lesions involving different organs and systems, which are usually serious and lead to life-threatening respiratory or circulatory dysfunction. Traumatic stress in the polytraumatized patient results in many metabolic changes that are evident from the first days, but usually persist for weeks, requiring adequate nutritional support as they influence outcomes. Nutritional treatment should be a priority in the comprehensive treatment of polytraumatized patients since it attenuates the metabolic response to trauma and prevents the deterioration of body reserves. It should be noted that some patients present previous nutritional risk. Nutritional intervention should be considered at the same level as any other therapy that supports organic functions, especially in patients in the intensive care unit. Nutritional intervention in polytraumatized patients is a pillar of treatment that has multiple benefits and can improve prognosis. All efforts must be aimed at the early detection of malnourished patients at nutritional risk and providing timely therapies that improve clinical outcomes.

Prognostic value of neutrophil-lymphocyte ratio in out-of-hospital cardiac arrest patients receiving targeted temperature management: An observational cohort study

Out-hospital cardiac arrest (OHCA) is a major cause of mortality and morbidity worldwide. The magnitude of the post-resuscitation inflammatory response is closely related to the severity of the circulatory dysfunction. Currently, targeted temperature management (TTM) has become an essential part of the post-resuscitation care for unconscious OHCA survivors. Some novel prognostic inflammatory markers may help predict outcomes of OHCA patients after TTM. A retrospective observational cohort study of 65 OHCA patients treated with TTM was conducted in a tertiary hospital in Taiwan. The primary outcome measure was in-hospital mortality. Baseline and post-TTM neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte (PLR), and the systemic immune inflammation index (SII) were identified as potential predictors. These patients had a mean age of 62.2±17.0 years. Among the total sample, 53.8% had an initial shockable rhythm and 61.5% had a presumed cardiac etiology. The median resuscitation duration was 20min (IQR 13.5-28.5) and 60% received subsequent percutaneous coronary intervention. The mean baseline NLR, PLR and SII were 7.5±16.7, 118±207, 1395±3004, and the mean post-TTM NLR, PLR and SII were 15.0±11.6, 206±124, 2369±2569, respectively. Using multiple logistic regression analysis, post-TTM NLR was one of the independent factors which predicted in-hospital mortality (adjusted odds ratio (aOR): 1.249, 95% confidence interval (CI): 1.040-1.501, p=0.017). Post-TTM NLR is a predictor of in-hospital mortality in OHCA patients who underwent TTM.

Abstract 143: Sepsis And Risk Of Major Postoperative Vascular Complications

Introduction: Stroke, myocardial infarction (MI), and pulmonary embolism (PE) greatly increase postoperative morbidity and mortality. Sepsis has been linked to increased risk of major vascular events, but the risk related to sepsis exposure throughout the postoperative period is uncertain. Hypothesis: Perioperative sepsis exposure increases the 30-day risk of postoperative stroke, myocardial infarction (MI), and pulmonary embolism (PE). Methods: Data were obtained from the American College of Surgeons National Surgical Quality Improvement Program (NSQIP), a formulaic sampling of surgical cases from participating United States institutions that prospectively collects demographic, clinical, surgical and 30-day outcome data. Sepsis was defined by systemic inflammatory response syndrome with either positive blood culture or evidence for infection found intraoperatively, and severe sepsis/shock as sepsis with evidence of organ dysfunction or circulatory dysfunction. We used mixed-effects Cox proportional hazard models, treating type of surgery as a random effect, to estimate the hazard ratios for major vascular complications due to sepsis and severe sepsis/shock exposure, adjusting for otherrisk factors. Results: We studied 6,614,937 surgical procedures. There were 201,230 cases with sepsis and an additional 78,052 cases of severe sepsis/shock. Outcomes included 13,939 strokes, 23,600 MIs, 21,893 PEs, and 1690 cases with multiple major vascular complications. Exposure to sepsis (HR 1.98, 95% confidence interval 1.91 to 2.06) or severe sepsis/shock (HR 3.27, 3.14 to 3.40) increased the risk of major vascular complications with larger effect than other established risks. Sepsis improvement within the preoperative period was associated with reduced risk (HR 0.82, 0.77 to 0.88). These findings were consistent in separate models for each complication. Conclusions: Sepsis approximately doubles and severe sepsis or shock triples the 30-day postoperative risk of major vascular complications. Improvement in sepsis severity prior to operation is associated with a 20% risk reduction.

Considerations for Advanced Heart Failure Consultation in Individuals With Fontan Circulation: Recommendations From ACTION.

Individuals with Fontan circulation are at risk of late mortality from both cardiac and noncardiac causes. Despite the known risk of mortality, referral indications for advanced heart failure care vary between centers, and many individuals die from Fontan circulation-related complications either after late consideration for advanced heart failure therapies or having never seen a heart failure specialist. There is a critical need for guidelines to direct appropriately timed referral for advanced heart failure consultation. The Advanced Cardiac Therapies Improving Outcomes Network (ACTION) Fontan Committee has developed recommended thresholds for advanced heart failure referral to guide primary cardiologists. These recommendations are divided into 4 categories of clinical Fontan circulatory dysfunction including (1) cardiac/systemic ventricular dysfunction, (2) Fontan pathway dysfunction, (3) lymphatic dysfunction, and (4) extracardiac dysfunction.

Midodrine versus Albumin to Prevent Paracentesis Induced Circulatory Dysfunction in Acute on Chronic Liver Failure Patients in the Outpatient Clinic–a Randomized Controlled Trial

Paracentesis-induced circulatory disturbance (PICD) occurs in 12-20% of patients receiving human albumin for large-volume paracentesis, and can occur at lower than five liter paracentesis in acute-on-chronic liver failure (ACLF). Albumin infusions are associated with higher costs and more prolonged daycare admissions. The aim of the study was to determine if oral midodrine-hydrochloride can prevent PICD in these patients by increasing the mean arterial pressure (MAP). This open-labeled randomized controlled trial included ACLF patients undergoing paracentesis between 3 and 5L, who were randomized to receive either 20% human albumin or midodrine hydrochloride 7.5mg thrice daily for three days, 2h before paracentesis. MAP was recorded daily. The primary outcome was the plasma renin activity (PRA) on day six, and a 50% increase from baseline was considered PICD. 183 consecutive patients of ACLF were screened, and 50 patients were randomized to either arms. Alcohol was the most common underlying cause of cirrhosis. On day 6, PRA was non-significantly (P=0.056) higher in the midodrine group. The absolute change of PRA between the two groups was not significant (P= 0.093). Four (16%) patients in the albumin group and five (20%) in the midodrine group developed PICD. MAP increase was not different between the albumin and midodrine arms (P= 0.851). Midodrine was found to be more cost-effective. Three days of oral midodrine is as effective as a human-albumin infusion in preventing PICD in ACLF patients undergoing paracentesis lesser than that done in large volume paracentesis.

Human Albumin Infusion for the Management of Liver Cirrhosis and Its Complications: An Overview of Major Findings from Meta-analyses.

The role of human albumin (HA) infusion in cirrhotic patients has been increasingly recognized. This paper aims to summarize the evidence from meta-analyses regarding HA infusion for the management of cirrhosis and its complications. A systematic search in the PubMed, EMBASE, and Cochrane library databases, and in reference lists was conducted. All relevant meta-analyses were identified and their findings were reviewed. The Assessment of Multiple Systematic Reviews 2 (AMSTAR-2) checklist was used to evaluate the methodological quality and the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) system to assess the quality of evidence for significant outcomes. Among 300 papers initially identified, 18 meta-analyses have been included. Short- and long-term HA infusion at high doses decreased the mortality of patients with decompensated cirrhosis. In cirrhotic patients with ascites, long-term HA infusion reduced the recurrence of ascites, but not mortality. In cirrhotic patients undergoing large-volume paracentesis (LVP), HA infusion reduced the incidence of post-paracentesis circulatory dysfunction and hyponatremia, but not mortality or renal impairment. In cirrhotic patients with overt hepatic encephalopathy (HE), HA infusion improved the severity of overt HE, but not overall mortality. In cirrhotic patients with spontaneous bacterial peritonitis (SBP), but not those with non-SBP infections, HA infusion reduced the mortality and renal impairment. In cirrhotic patients with type-1 hepatorenal syndrome (HRS), an increment of 100g in cumulative HA dose increased 1.15-fold survival, but not HRS reversal. In these meta-analyses, the quality of methodology was low or critically low, and that of the evidence was from very low to moderate. Based on the limited evidence from these meta-analyses, HA infusion appears to be beneficial in cirrhotic patients with ascites, overt HE, and SBP and in those undergoing LVP, but not in those with non-SBP infections.

Efficacy and safety of extracorporeal membrane oxygenation for burn patients: a comprehensive systematic review and meta-analysis.

Respiratory and circulatory dysfunction are common complications and the leading causes of death among burn patients, especially in severe burns and inhalation injury. Recently, extracorporeal membrane oxygenation (ECMO) has been increasingly applied in burn patients. However, current clinical evidence is weak and conflicting. This study aimed to comprehensively evaluate the efficacy and safety of ECMO in burn patients. A comprehensive search of PubMed, Web of Science and Embase from inception to 18 March 2022 was performed to identify clinical studies on ECMO in burn patients. The main outcome was in-hospital mortality. Secondary outcomes included successful weaning from ECMO and complications associated with ECMO. Meta-analysis, meta-regression and subgroup analyses were conducted to pool the clinical efficacy and identify influencing factors. Fifteen retrospective studies with 318 patients were finally included, without any control groups. The commonest indication for ECMO was severe acute respiratory distress syndrome (42.1%). Veno-venous ECMO was the commonest mode (75.29%). Pooled in-hospital mortality was 49% [95% confidence interval (CI) 41-58%] in the total population, 55% in adults and 35% in pediatrics. Meta-regression and subgroup analysis found that mortality significantly increased with inhalation injury but decreased with ECMO duration. For studies with percentage inhalation injury ≥50%, pooled mortality (55%, 95% CI 40-70%) was higher than in studies with percentage inhalation injury <50% (32%, 95% CI 18-46%). For studies with ECMO duration ≥10days, pooled mortality (31%, 95% CI 20-43%) was lower than in studies with ECMO duration <10days (61%, 95% CI 46-76%). In minor and major burns, pooled mortality was lower than in severe burns. Pooled percentage of successful weaning from ECMO was 65% (95% CI 46-84%) and inversely correlated with burn area. The overall rate of ECMO-related complications was 67.46%, and infection (30.77%) and bleedings (23.08%) were the two most common complications. About 49.26% of patients required continuous renal replacement therapy. ECMO seems to be an appropriate rescue therapy for burn patients despite the relatively high mortality and complication rate. Inhalation injury, burn area and ECMO duration are the main factors influencing clinical outcomes.

The progression of hepatorenal syndrome-acute kidney injury in acute alcohol-associated hepatitis: renal outcomes after liver transplant.

Hepatorenal syndrome-acute kidney injury (HRS-AKI) is a complication of advanced liver disease in patients with ascites and circulatory dysfunction. Little data remain on the relationship between HRS-AKI outcomes and different etiologies of liver disease post-liver transplant (LT). The primary aim was to evaluate the effect of HRS-AKI on renal outcomes in patients with acute alcohol-associated hepatitis (AAH) compared to chronic liver disease (CLD) after LT. The secondary aim was to evaluate the impact of acuity and chronicity of alcohol-associated liver disease in patients with HRS-AKI post-LT renal outcomes. A retrospective observational study of patients undergoing urgent inpatient liver transplant evaluation (LTE) for cirrhosis and AAH at single academic LT center between October 2017 and July 2021 was conducted. Patients with HRS-AKI were selected based on indication for LTE: acute AAHHRS or CLDHRS. CLDHRS was categorized by disease etiology: cirrhosis due to alcohol (A-CLDHRS) versus cirrhosis from other causes (O-CLDHRS). CLD patients without HRS-AKI were labeled CLDno HRS. A total of 210 subjects underwent LTE; 25% were evaluated for AAH and 75% were evaluated for CLD. Hepatorenal syndrome was more common in subjects evaluated for AAH (37/47) than CLD (104/163) (78.7 versus 63.8%, p = 0.04). For the primary outcome, AAHHRS subjects required ⩾30 days post-LT renal replacement therapy (RRT) more often than subjects with CLDHRS (p = 0.02) and CLDno HRS (p < 0.01). There was no significant difference in other forms of long-term renal outcomes including kidney transplant referral and kidney transplant among cohorts. In subgroup analysis, 30-days post-LT RRT was more common in AAHHRS than in A-CLDHRS (p = 0.08). Logistic regression showed that AAHHRS conferred a 20× and 3.3× odds of requiring ⩾30 days post-LT RRT compared to CLDno HRS and CLDHRS, respectively. Postoperative complications were similar across cohorts, but had a significant effect on 30-day renal outcome post-LT. Patients with AAH were more likely to develop HRS and require RRT pre- and post-LT at our center. The etiology of hepatic decompensation and postoperative complications affect renal recovery post-LT. The systemic inflammation of AAH in addition to conditions favoring renal hypoperfusion may contribute to the unfavorable outcomes of HRS-AKI after LT in this patient population.

Serum copeptin is associated with major complications of liver cirrhosis and spontaneous bacterial peritonitis.

We aimed to investigate the possible association between serum copeptin and complications of liver cirrhosis, including its potential role as a stress biomarker in spontaneous bacterial peritonitis (SBP). This cross-sectional study included 89 cirrhotic ascitic patients (37 with SBP and 52 without SBP) admitted to Sohag University Hospitals, Egypt, between June 2021 and February 2022. Serum copeptin was measured in all patients, and its association with SBP and other complications of liver cirrhosis was investigated. Serum copeptin was significantly elevated in patients with SBP compared to those without SBP (p = 0.032) and significantly correlated with ascitic fluid study parameters, systemic inflammatory markers, and liver, renal, and circulatory functions. Serum copeptin and C-reactive protein (CRP) were independent risk factors for the presence of SBP. Serum copeptin detects SBP at a cut-off value of 9 pmol/l, with sensitivity and specificity of 73% and 64%, respectively. Serum copeptin was significantly associated with hepatic encephalopathy, gastrointestinal bleeding, hepatorenal syndrome, and larger amounts of ascites. Serum copeptin is an independent risk factor for the presence of SBP and significantly increased in patients presented with major complications of liver cirrhosis, demonstrating its ability to reflect circulatory dysfunction and systemic inflammation.

CO19 Adjunctive Albumin Infusion During Large-Volume Paracentesis May Improve Days to Next Hospital Readmission in Cirrhotic Patients

Ascites is a common complication in patients with cirrhosis, often requiring large-volume (>5 L) paracentesis (LVP). Albumin is recommended by the American Association for the Study of Liver Diseases to be infused at the time of LVP to mitigate the risks of post-paracentesis circulatory dysfunction. This research examined the time to hospital readmission after discharge among patients who received and did not receive adjunctive albumin during an LVP procedure.

Midodrine and albumin as a possible "winning pair" in managing paracentesis-induced circulatory dysfunction: a clinical case report.

Paracentesis-induced circulatory dysfunction (PICD) is a "silent killer syndrome" occurring after large volume paracenteses (LVPs). We here report an unusual case of PICD induced by right heart failure recognized and managed successfully. A 60-year-old woman was admitted to our Emergency Department for worsening dyspnea and hypoxia. Her medical history enclosed a chronic heart failure with reduced ejection fraction and post-stroke dysarthria associated to right hemiplegia. Clinical and laboratory examination defined a severe right-heart failure unresponsive to high-dose diuretic therapy. Diagnostic and therapeutic paracentesis was thus performed determining, initially, a progressive normalization of the abdominal volume, followed, subsequently, by a severe hypotension associated with an acute kidney injury (AKI) combined with severe hyponatremia associated with a normal cardiac output. In the hypothesis of a PICD, abdominal drainage and diuretic therapy were interrupted, reninemia sampling was performed, resulting in diagnostic, and treatment with albumin and norepinephrine was started. The latter was tapered and then replaced with Midodrine that conferred the possibility to reach clinical and laboratory stability, allowing relocation in a cardiological rehabilitation. PICD represents an independent predictor of mortality. Midodrine's prophylactic use in PICD has been suggested as a cheaper alternative to albumin, as it appears to improve renal perfusion and reduce ascites with better clinical handling, as demonstrated in our patient. Our clinical case wants to show how not all PICDs are secondary to hepatic dysfunctions with Midodrine playing a possible therapeutic role by counteracting the pathophysiological mechanism in a rapid and non-invasive way, representing a valid therapeutic option in adjunction to albumin.

Transjugular intrahepatic portosystemic shunt in portal hypertension: How to go further while staying on track?

Transjugular intrahepatic portosystemic shunt in portal hypertension: How to go further while staying on track?

Choroid plexus perfusion and bulk cerebrospinal fluid flow across the adult lifespan

The choroid plexus (ChP) comprises a collection of modified ependymal cells that play an important role in the production of brain cerebrospinal fluid (CSF), and ChP perfusion aberrations have been implicated in a range of cerebrovascular and neurodegenerative disorders. To provide an exemplar for the growing interest in ChP activity, we evaluated ChP perfusion and bulk CSF flow cross-sectionally across the healthy adult lifespan. Participants (n = 77; age range = 21–86 years) were scanned at 3T using T1-weighted, T2-weighted-FLAIR, perfusion-weighted pCASL, and phase contrast MRI to calculate ChP anatomy, perfusion, and aqueductal CSF flow, respectively. Regression models were applied to evaluate aging effects on ChP volume and ChP perfusion in the lateral ventricles, as well as CSF flow. ChP volume (mean ± std = 2.81 ± 1.1 cm3) increased (p < 0.001), ChP perfusion (36.3 ± 8.6 mL/100 g/min) decreased (p = 0.0078), and ChP total blood flow (1.13 ± 0.34 mL/min) increased (p < 0.001) with age. Cranial-to-caudal net CSF flow (0.245 ± 0.20 mL/min) decreased, absolute CSF flow (4.86 ± 2.96 mL/min) increased, and CSF regurgitant fraction (0.87 ± 0.126) increased with age (all: p < 0.001). ChP perfusion was directly related to net cranial-to-caudal CSF flow through the aqueduct (p = 0.033). The implications of these findings are discussed in the context of the growing literature on CSF circulatory dysfunction in neurodegeneration and cerebrovascular disease.

S1191 Treatment Response to Terlipressin Plus Albumin Varies by Precipitating Factor in Patients With Hepatorenal Syndrome Type 1

Introduction: Hepatorenal syndrome (HRS) is a rapidly progressive form of renal failure that occurs in patients (pts) with advanced cirrhosis. Many cases of HRS are believed to be precipitated by an event such as infection, diuretic use, large volume paracentesis (LVP), or gastrointestinal bleeding (GIB). Terlipressin (TERLI) significantly reverses the renal and circulatory dysfunction in pts with HRS more effectively than placebo (PBO), although response rates may vary based on the presence of an underlying precipitant at baseline. Methods: Using pooled data from 3 Phase III PBO-controlled studies (OT-0401, REVERSE, and CONFIRM), the incidence of HRS reversal—defined as >1 serum creatinine value of ≤1.5 mg/dL while on treatment—and HRS reversal without renal replacement therapy (RRT) by Day 30 after treatment with TERLI + albumin (n=352) vs PBO + albumin (n=256) was evaluated in subgroups of pts with HRS who presented with either infection, LVP (with or without diuretic use), GIB, or no identifiable precipitant. Results: In the pooled population, pt age (mean±SD) was 54±11 years in each of the TERLI and PBO groups; 61% vs 65% of pts, respectively, were male; baseline MELD score was 33±6 in each group; and alcohol was the cause of cirrhosis in 60% vs 59% of pts, respectively. HRS reversal was achieved by 33% of pts in the TERLI group vs 16% in the PBO group (P< .001). HRS reversal without RRT was higher in the TERLI group (30%) vs the PBO group (15%; P< .001). Pts in the TERLI group who presented with infection had a higher incidence of HRS reversal and HRS reversal without RRT vs the PBO group (P=.018 and P=.014, respectively; Table). For LVP/diuretic use, HRS reversal was higher in the TERLI group vs the PBO group (P=.025), while a higher trend for HRS reversal without RRT was observed in the TERLI group (P=.077). HRS reversal and HRS reversal without RRT were similar between groups in pts with GIB, although the numbers in this group were small (P=.347 and P=.234, respectively). HRS reversal and HRS reversal without RRT were higher in TERLI-treated pts who presented without an identifiable precipitant vs the PBO group (P< .001 and P=.007, respectively). Conclusion: TERLI-treated pts who presented with infection, LVP, or no identifiable precipitant for HRS achieved HRS reversal and avoided RRT more frequently than pts in the PBO group. Few pts who presented with GIB achieved HRS reversal, regardless of treatment. Precipitants for HRS may modify the clinical response to TERLI in pts with HRS. Table 1. - HRS Reversal and HRS Reversal without RRT through Day 30 by Possible Precipitating Factors for HRS and Treatment Group, Pooled ITT Population Parameter Infection LVP and/orDiuretic Treatment GIB No Identifiable Precipitant TERLI (n=59) PBO (n=44) P Value* TERLI (n=83) PBO (n=59) P Value* TERLI (n=19) PBO (n=16) P Value* TERLI (n=177) PBO (n=107) P Value* HRS Reversal† 24 (41) 8 (18) .018 30 (36) 11 (19) .025 4 (21) 1 (6) .347 61 (35) 17 (16) < .001 HRS Reversal without RRT through Day 30‡ 21 (36) 6 (14) .014 26 (31) 10 (17) .077 3 (16) 0 .234 54 (31) 17 (16) .007 Data are presented as n (%). Data are pooled from the Phase III studies: OT-0401, REVERSE, and CONFIRM.*Calculated using a Fisher’s exact test.†The incidence of HRS reversal is defined as at least 1 SCr value of ≤1.5 mg/dL on treatment (up to 24 hours after the last dose of study medication). Any SCr values obtained posttransplant or RRT are excluded.‡For OT-0401 and CONFIRM, dates/times are used to determine 30 days. For REVERSE, RRT is recorded with dates/times through the end of the treatment period at the Day 30 visits without an RRT date.GIB, gastrointestinal bleeding; HRS, hepatorenal syndrome; ITT, intent-to-treat; LVP, large volume paracentesis; PBO, placebo; RRT, renal replacement therapy; SCr, serum creatinine; TERLI, terlipressin.

Cigarette smoke exposure reduces hemorrhagic shock induced circulatory dysfunction in mice with attenuated glucocorticoid receptor function.

IntroductionWe previously showed that attenuated glucocorticoid receptor (GR) function in mice (GRdim/dim) aggravates systemic hypotension and impairs organ function during endotoxic shock. Hemorrhagic shock (HS) causes impaired organ perfusion, which leads to tissue hypoxia and inflammation with risk of organ failure. Lung co-morbidities like chronic obstructive pulmonary disease (COPD) can aggravate tissue hypoxia via alveolar hypoxia. The most common cause for COPD is cigarette smoke (CS) exposure. Therefore, we hypothesized that affecting GR function in mice (GRdim/dim) and pre-traumatic CS exposure would further impair hemodynamic stability and organ function after HS.MethodsAfter 3 weeks of CS exposure, anesthetized and mechanically ventilated GRdim/dim and GR+/+ mice underwent pressure-controlled HS for 1h via blood withdrawal (mean arterial pressure (MAP) 35mmHg), followed by 4h of resuscitation with re-transfusion of shed blood, colloid fluid infusion and, if necessary, continuous intravenous norepinephrine. Acid–base status and organ function were assessed together with metabolic pathways. Blood and organs were collected at the end of the experiment for analysis of cytokines, corticosterone level, and mitochondrial respiratory capacity. Data is presented as median and interquartile range.ResultsNor CS exposure neither attenuated GR function affected survival. Non-CS GRdim/dim mice had a higher need of norepinephrine to keep target hemodynamics compared to GR+/+ mice. In contrast, after CS exposure norepinephrine need did not differ significantly between GRdim/dim and GR+/+ mice. Non-CS GRdim/dim mice presented with a lower pH and increased blood lactate levels compared to GR+/+ mice, but not CS exposed mice. Also, higher plasma concentrations of some pro-inflammatory cytokines were observed in non-CS GRdim/dim compared to GR+/+ mice, but not in the CS group. With regards to metabolic measurements, CS exposure led to an increased lipolysis in GRdim/dim compared to GR+/+ mice, but not in non-CS exposed animals.ConclusionWhether less metabolic acidosis or increased lipolysis is the reason or the consequence for the trend towards lower catecholamine need in CS exposed GRdim/dim mice warrants further investigation.

Fibrinolytic Enzyme - An Overview.

Cardiovascular diseases, like coronary heart disease or artery disorders (arteriosclerosis, including artery solidification), heart failure (myocardial infarction), arrhythmias, congestive heart condition, stroke, elevated vital signs (hypertension), rheumatic heart disorder, and other circulatory system dysfunctions are the most common causes of death worldwide. Cardiovascular disorders are treated with stenting, coronary bypass surgery grafting, anticoagulants, antiplatelet agents, and other pharmacological and surgical procedures; however, these have limitations due to their adverse effects. Fibrinolytic agents degrade fibrin through enzymatic and biochemical processes. There are various enzymes that are currently used as a treatment for CVDs, like streptokinase, nattokinase, staphylokinase, urokinase, etc. These enzymes are derived from various sources, like bacteria, fungi, algae, marine organisms, plants, snakes, and other organisms. This review deals with the fibrinolytic enzymes, their mechanisms, sources, and their therapeutic potential.

Practice guidance for the use of terlipressin for liver cirrhosis-related complications (2021)

Liver cirrhosis is a major global health burden worldwide due to its high risk of morbidity and mortality. Role of terlipressin for the management of liver cirrhosis related complications has been recognized during recent years. This paper aims to develop evidence-based clinical practice guidance on the use of terlipressin for liver cirrhosis related complications. Hepatobiliary Study Group of Chinese Society of Gastroenterology of Chinese Medical Association and Hepatology Committee of Chinese Research Hospital Association have invited gastroenterologists, hepatologists, infectious disease specialists, surgeons, and clinical pharmacists to formulate the clinical practice guidance based on comprehensive literature review and experts' clinical experiences. Overall, 10 major statements regarding efficacy and safety of terlipressin in liver cirrhosis were proposed. Terlipressin can be beneficial for the management of cirrhotic patients with acute variceal bleeding and hepatorenal syndrome (HRS). However, the evidence regarding the use of terlipressin in cirrhotic patients with ascites, post-paracentesis circulatory dysfunction, and bacterial infections and in those undergoing hepatic resection and liver transplantation remains insufficient. Terlipressin-related adverse events, mainly including gastrointestinal symptoms, electrolyte disturbance, and cardiovascular and respiratory adverse events, should be closely monitored. The current clinical practice guidance supports the use of terlipressin for gastroesophageal variceal bleeding and HRS in liver cirrhosis. High-quality studies are needed to further clarify its potential effects in other liver cirrhosis related complications.

Midodrine in Liver Cirrhosis With Ascites: A Systematic Review and Meta-Analysis.

Ascites is the most common complication of liver cirrhosis. Midodrine is a vasoconstrictor that improves splanchnic and systemic hemodynamics, reduces ascites, and improves clinical outcomes. Here, we aimed to examine the role of midodrine in cirrhosis-related ascites.Scopus, Embase, PubMed, and PubMed Central databases were searched for relevant randomized controlled trials comparing midodrine with other interventions in patients with cirrhotic ascites on November 25, 2020, using appropriate keywords like “midodrine”, “ascitic cirrhosis”, “peritoneal paracentesis” and suitable Boolean operators. Odds ratio (OR) and mean difference (MD) were used to analyze pool data as appropriate with a 95% confident interval (CI).A total of 14 studies were included in our analysis including 1199 patients. The addition of midodrine resulted in statistically significant improvement in mean arterial pressure (MAP) (MD, 3.95 mmHg; 95% CI, 1.53-6.36) and MELD (Model for End-Stage Liver Disease) score (MD, -1.27; 95% CI, -2.49 to -0.04) compared to standard medical treatment (SMT). There was also a significant improvement in plasma renin activity and plasma aldosterone concentration. However, there was no significant improvement in mortality or serum creatinine compared to SMT. In addition, there was no statistically significant improvement in MAP, plasma renin activity, plasma aldosterone concentration, MELD score, overall mortality, and paracentesis-induced circulatory dysfunction comparing midodrine with albumin.Midodrine alone leads to significant improvement in various clinical parameters in patients with cirrhotic ascites compared to standard medical care. At the same time, it was found to be non-inferior to albumin. Therefore, further well-designed studies need to be carried out on midodrine in addition to albumin for optimal clinical benefits among patients with ascites due to cirrhosis.

Study to Explore the Association of the Renin-Angiotensin System and Right Ventricular Function in Mechanically Ventilated Patients.

Background: Right ventricular (RV) dysfunction is associated with pulmonary vasoconstriction in mechanically ventilated patients. Enhancing the activity of angiotensin-converting enzyme 2 (ACE2), a key enzyme of the renin-angiotensin system (RAS), using recombinant human ACE2 (rhACE2) could alleviate RAS-mediated vasoconstriction and vascular remodeling. Methods: This prospective observational study investigated the association between concentrations of RAS peptides (Ang II or Ang(1–7)) and markers of RV function, as assessed by echocardiography (ratio of RV to left ventricular end-diastolic area, interventricular septal motion, and pulmonary arterial systolic pressure (PASP)). Results: Fifty-seven mechanically ventilated patients were enrolled. Incidence rates of acute cor pulmonale (ACP) and pulmonary circulatory dysfunction (PCD) were consistent with previous studies. In the 45 evaluable participants, no notable or consistent changes in RAS peptides concentration were observed over the observation period, and there was no correlation between Ang II concentration and either PASP or RV size. The model of the predicted posterior distributions for the pre- and post-dose values of Ang II demonstrated no change in the likelihood of PCD after hypothetical dosing with rhACE2, thus meeting the futility criteria. Similar results were observed with the other RAS peptides evaluated. Conclusions: Pre-defined success criteria for an association between PCD and the plasma RAS peptides were not met in the mechanically ventilated unselected patients.

Peripapillary circulatory dysfunction precedes structural loss in treatment-naive diabetic retinopathy.

The aim of this study was to compare the timing of peripapillary vascular damage between functional and structural parameters and examine their involvement with neurovascular coupling at different stages of diabetic retinopathy (DR). One hundred ninety eyes of 143 patients with type 2 diabetes mellitus (DM) and 88 healthy control eyes were enrolled. Eyes of DM patients were divided into 3 stages with no diabetic retinopathy (NDR), non-proliferative diabetic retinopathy (NPDR), and proliferative diabetic retinopathy (PDR). NPDR and PDR eyes were treatment-naive. OCT angiography was used to calculate radial peripapillary capillary (RPC)-flux index (FI) and RPC-perfusion density (PD). Spectral domain OCT was used to measure retinal nerve fiber layer (RNFL) thickness within the corresponding RPC areas. RPC-FI significantly decreased in NDR eyes compared to control eyes and thereafter remained unchanged among DM (NDR, NPDR, and PDR) eyes. In contrast, RPC-PD stayed unaltered between control and NDR eyes and significantly decreased in NPDR followed by PDR eyes at similar levels. From control to NPDR eyes, RNFL thickness showed positive correlations with both RPC-FI and RPC-PD, indicative of functional and structural neurovascular coupling. These vascular parameters were also correlated with each other in control and NPDR eyes but not NDR eyes, consistent with the difference in the timing of vascular damage between functional and structural parameters. Circulatory dysfunction preceded structural loss while maintaining peripapillary neurovascular coupling during progression of DR stages. RPC-FI would likely be more sensitive than RPC-PD in detecting early vascular damage in DR.