Effect of geography on the use of ultrafiltration during cardiac surgery with cardiopulmonary bypass.

BACKGROUND: Ultrafiltration (UF) is a common practice during cardiopulmonary bypass (CPB) where it is used as a blood management strategy to reduce red blood cell (RBC) transfusion, minimize adverse effects of hemodilution, and reduce proinflammatory mediators. However, its clinical utilization has been shown to vary throughout the continents. PURPOSE: The purpose of this investigation was to assess the distribution of UF use across the United States. DATA COLLECTION: Data on UF use during cardiac surgery was obtained from a national (United States) perfusion database for adult cardiac procedures performed from January 2016 through December 2018. STUDY SAMPLE: Four geographical regions were established: Northeast (NE), South (SO), Midwest (MW) and West (WE). The primary endpoint was the use of UF with secondary endpoints UF volume, CPB and anesthesia asanguineous volumes, intraoperative allogeneic RBC transfusion, nadir hematocrit and urine output (UO). 92,859 adult cardiac cases from 191 hospitals were reviewed. RESULTS: The NE and the WE had similar usages of UF (59.9% and 59.7% respectively), which were higher than the MW and the SO (38.6% and 34.9%, p < .001). When UF was utilized, the median [IQR] volume removed was highest in the NE (1900 [1200-2800]mL), and similar in all other regions (WE 1500 [850-2400 mL, MW 1500 [900-2300]mL and SO 1500 [950-2200]mL, p < .001. Median total UO was lowest in the NE 400 [210,650]mL vs all other regions (p < .001), and remained so when indexed by patient weight and operative time (NE-0.8 [0.5, 1.3]mL/kg/hour, MW-1.1 [0.7, 1.8] mL/kg/hour, SO-1.3 [0.8, 2.0]mL/kg/hour, WE-1.1 [0.7, 1.3]mL/kg/hour, p < .001. Intraoperative RBC transfusion rate was highest in the SO (21.3%) and WE (20.5%), while similar rates seen in the NE (16.2%) and MW (17.6%), p < .001. CONCLUSIONS: Across the United States there is geographic variation on the use of UF. Further research is warranted to investigate why these practice variations exist and to better understand and determine their reasons for use.

Establishment of a national quality improvement process on oxygen delivery index during cardiopulmonary bypass.

Targeted oxygen delivery during cardiopulmonary bypass (CPB) has received significant attention due to its influence on patient outcomes, especially in mitigating acute kidney injury. While it has gained popularity in select institutions, there remains a gap in establishing it globally across multiple centers. The purpose of this investigation was to describe the development of a quality improvement process of targeted oxygen delivery during CPB across hospitals throughout the United States. A systematic approach to utilize oxygen delivery index (DO2i) as a key performance indicator within hospitals serviced by a national provider of perfusion services. The process included a review of the current literature on DO2i, which yielded a target nadir value (272 mL/min/m2) and an area under the curve (DO2i272AUC) cut off of 632. All data is displayed on a dashboard with results categorized across multiple levels from system-wide to individual clinician performance. From January 2020 through December 2022, DO2i data from 91 hospitals and 11,165 coronary artery bypass graft procedures were collected. During this period the monthly proportion of DO2i measurements above the target nadir DO2i272 ranged from 60.5% to 78.4% with a mean+/-SD of 70.8 +/- 4.2%. Binary logistic regression for the first 7 months following monthly DO2i performance reporting has shown a statistically significant positive linear trend in the probability of achieving the target DO2i272 (p < .001), with a crude increase of approximately 7.8% for DO2i272AUC, and a 73.8% success rate (p < .001). A survey was sent to all individuals measuring oxygen delivery during CPB to assess why a target DO2i272 could not be reached. The two most common responses were an 'inability to improve CPB flow rates' and 'restrictive allogeneic red blood cell transfusion policies'. This study demonstrates that targeting a minimum level of oxygen delivery can serve as a key performance indicator during CPB using a structured quality improvement process.

Variation in outcomes with extracorporeal membrane oxygenation in the era of coronavirus: A multicenter cohort evaluation.

Extracorporeal membrane oxygenation (ECMO) is used in critically ill patients with coronavirus disease 2019 (COVID-19) with acute respiratory distress syndrome unresponsive to other interventions. However, a COVID-19 infection may result in a differential tolerance to both medical treatment and ECMO management. The aim of this study was to compare outcomes (mortality, organ failure, circuit complications) in patients on ECMO with and without COVID-19 infection, either by venovenous (VV) or venoarterial (VA) cannulation. This is a multicenter, retrospective analysis of a national database of patients placed on ECMO between May 2020 and January 2022 within the United States. Nine-hundred thirty patients were classified as either Pulmonary (PULM, n = 206), Cardiac (CARD, n = 279) or COVID-19 (COVID, n = 445). Patients were younger in COVID groups: PULM = 48.4 ± 15.8 years versus COVID = 44.9 ± 12.3 years, p = 0.006, and CARD = 57.9 ± 15.4 versus COVID = 46.5 ± 11.8 years, p < 0.001. Total hours on ECMO were greatest for COVID patients with a median support time two-times higher for VV support (365 [101, 657] hours vs 183 [63, 361], p < 0.001), and three times longer for VA support (212 [99, 566] hours vs 70 [17, 159], p < 0.001). Mortality was highest for COVID patients for both cannulation types (VA-70% vs 51% in CARD, p = 0.041, and VV-59% vs PULM-42%, p < 0.001). For VA supported patients hepatic failure was more often seen with COVID patients, while for VV support renal failure was higher. Circuit complications were more frequent in the COVID group as compared to both CARD and PULM with significantly higher circuit change-outs, circuit thromboses and oxygenator failures. Anticoagulation with direct thrombin inhibitors was used more often in COVID compared to both CARD (31% vs 10%, p = 0.002) and PULM (43% vs 15%, p < 0.001) groups. This multicenter observational study has shown that COVID patients on ECMO had higher support times, greater hospital mortality and higher circuit complications, when compared to patients managed for either cardiac or pulmonary lesions.

Patterns of Plumericin Concentration in Leaves of Himatanthus tarapotensis (Apocynaceae) and Its Interactions with Herbivory in the Peruvian Amazon.

We explored the concentration patterns of the bioactive metabolite plumericin produced by Himatanthus tarapotensis (Apocynaceae) under different edaphic conditions and variations in rainfall intensity, as well as its potential role in the chemical defense against insect herbivores. Values of plumericin concentration from leaves were obtained by High-Performance Liquid Chromatography, and evaluated as a function of differences in soil types, variation of precipitation, and variation of the abundance of insect herbivores, using first a Repeated Measures Correlation (rmcorr) and then a Generalized Linear Mixed Model (GLMM) analysis. Plumericin concentration is highly variable among plants, but with a significantly higher concentration in plants growing on clay soil compared to that of the white-sand soil habitat (p < 0.001). Plumericin concentration is not affected by precipitation. The caterpillar of Isognathus leachii (Lepidoptera: Sphingidae) is the most conspicuous herbivore of H. tarapotensis, and its presence is continuous but not related to plumericin concentration, probably because of its capacity to elude the chemical defense of this plant. Nevertheless, our multivariate model revealed that plumericin concentration is related to the abundance of Hymenoptera (Formicidae), and this relationship is significantly influenced by the soil parameters of carbon percentage, clay percentage, and phosphorous percentage (p < 0.001). Plumericin is a mediating agent in the interaction between H. tarapotensis and its natural environment. Variation in plumericin concentration would be induced by the abundance of Hymenoptera (Formicidae), probably as a chemical response against these insects, and by differences in soil nutrient availability.

Multi-institutional Analysis of 505 Patients With Coronavirus Disease-2019 Supported With Extracorporeal Membrane Oxygenation: Predictors of Survival.

BACKGROUND: We reviewed our experience with 505 patients with confirmed coronavirus disease-2019 (COVID-19) supported with extracorporeal membrane oxygenation (ECMO) at 45 hospitals and estimated risk factors for mortality. METHODS: A multi-institutional database was created and used to assess all patients with COVID-19 who were supported with ECMO. A Bayesian mixed-effects logistic regression model was estimated to assess the effect on survival of multiple potential risk factors for mortality, including age at cannulation for ECMO as well as days between diagnosis of COVID-19 and intubation and days between intubation and cannulation for ECMO. RESULTS: Median time on ECMO was 18 days (interquartile range, 10-29 days). All 505 patients separated from ECMO: 194 patients (38.4%) survived and 311 patients (61.6%) died. Survival with venovenous ECMO was 184 of 466 patients (39.5%), and survival with venoarterial ECMO was 8 of 30 patients (26.7%). Survivors had lower median age (44 vs 51 years, P < .001) and shorter median time interval from diagnosis to intubation (7 vs 11 days, P = .001). Adjusting for several confounding factors, we estimated that an ECMO patient intubated on day 14 after the diagnosis of COVID-19 vs day 4 had a relative odds of survival of 0.65 (95% credible interval, 0.44-0.96; posterior probability of negative effect, 98.5%). Age was also negatively associated with survival: relative to a 38-year-old patient, we estimated that a 57-year-old patient had a relative odds of survival of 0.43 (95% credible interval, 0.30-0.61; posterior probability of negative effect, >99.99%). CONCLUSIONS: ECMO facilitates salvage and survival of select critically ill patients with COVID-19. Survivors tend to be younger and have shorter time from diagnosis to intubation. Survival of patients supported with only venovenous ECMO was 39.5%.

The assessment of patients undergoing cardiac surgery for Covid-19: Complications occurring during cardiopulmonary bypass.

The outbreak of the novel coronavirus pandemic (COVID-19) has resulted in dramatic changes to the conduct of surgery both from a patient management perspective and in protecting healthcare providers. The current study reports on the status of COVID-19 infections in patients presenting for cardiac surgery with cardiopulmonary bypass (CPB) on circuit complications. A tracking process for monitoring the presence of COVID-19 in adult cardiac surgery patients was integrated into a case documentation system across United States hospitals where out-sourced perfusion services were provided. Assessment included infection status, testing technique employed, surgery status and CPB complications. Records from 5612 adult patients who underwent cardiac surgery between November 1, 2020 and January 18, 2021 from 176 hospitals were reviewed. A sub-cohort of coronary artery bypass graft patients (3283) was compared using a mixed effect binary logistic regression analysis. 4297 patients had negative test results (76.6%) while 49 (0.9%) tested positive for COVID-19, and unknown or no results were reported in 693 (12.4%) and 573 (10.2%) respectively. Coagulation complications were reported at 0.2% in the negative test results group versus 4.1% in the positive test result group (p < 0.001). Oxygenator gas exchange complications were 0.2% in the negative test results group versus 2.0% in the positive test results group (p = 0.088). Coronary artery bypass graft patients with a positive test had significantly higher risk for any CPB complication (p = 0.003) [OR 10.38, CI 2.18-49.53] then negative test patients [OR 0.01, CI 0.00-0.20]. The present study has shown that patients undergoing cardiac surgery with CPB who test positive for COVID-19 have higher CPB complication rate than those who test negative.

Indoloquinoxaline derivatives as promising multi-functional anti-Alzheimer agents.

To confront a disease like Alzheimer's disease having complex pathogenesis, development of multitarget-directed ligands has emerged as a promising drug discovery approach. In our endeavor towards the development of multitarget-directed ligands for Alzheimer's disease, a series of indoloquinoxaline derivatives were designed and synthesized. In vitro cholinesterase inhibition studies revealed that all the synthesized compounds exhibited moderate to good cholinesterase inhibitory activity. 6-(6-(Piperidin-1-yl)hexyl)-6H-indolo[2,3-b]quinoxaline 9f was identified as the most potent and selective BuChE inhibitor (IC50 = 0.96 µM, selectivity index = 0.17) that possessed 2 fold higher BuChE inhibitory activity compared to the commercially approved reference drug donepezil (IC50 = 1.87 µM). Moreover, compound 9f is also endowed with self-induced Aß1-42 aggregation inhibitory activity (51.24% inhibition at 50 µM concentration). Some of the compounds of the series also displayed moderate anti-oxidant activity. To perceive a putative binding mode of the compound 9f, molecular docking studies were carried out, and the results pointed out significant interactions of compound 9f with the enzymes in the binding sites of cholinesterases as well as Aß1-42. Additionally, compound 9f exhibited favorable in silico ADMET properties. Put together these findings project compound 9f as a potential multitarget-directed ligand in the direction of developing novel anti-AD drugs.Communicated by Ramaswamy H. Sarma.

Carbazole-based semicarbazones and hydrazones as multifunctional anti-Alzheimer agents.

With the aim to combat a multi-faceted neurodegenerative Alzheimer's disease (AD), a series of carbazole-based semicarbazide and hydrazide derivatives were designed, synthesized and assessed for their cholinesterase (ChE) inhibitory, antioxidant and biometal chelating activity. Among them, (E)-2-((9-ethyl-9H-carbazol-3-yl)methylene)-N-(pyridin-2-yl)hydrazinecarbothioamide (62) and (E)-2-((9-ethyl-9H-carbazol-3-yl)methylene)-N-(5-chloropyridin-2-yl)hydrazinecarbothioamide (63) emerged as the premier candidates with good ChE inhibitory activities (IC50 values of 1.37 µM and 1.18 µM for hAChE, IC50 values of 2.69 µM and 3.31 µM for EqBuChE, respectively). All the test compounds displayed excellent antioxidant activity (reduction percentage of DPPH values for compounds (62) and (63) were 85.67% and 84.49%, respectively at 100 µM concentration). Compounds (62) and (63) conferred specific copper ion chelating property in metal chelation study. Molecular docking studies of compounds (62) and (63) indicate strong interactions within the active sites of both the ChE enzymes. Besides that, these compounds also exhibited significant in silico drug-like pharmacokinetic properties. Thus, taken together, they can serve as a starting point in the designing of multifunctional ligands in pursuit of potential anti-AD agents that might further prevent the progression of ADs.Communicated by Ramaswamy H. Sarma.

Multi-institutional Analysis of 200 COVID-19 Patients Treated With Extracorporeal Membrane Oxygenation: Outcomes and Trends.

BACKGROUND: The role of extracorporeal membrane oxygenation (ECMO) in the management of patients with COVID-19 continues to evolve. The purpose of this analysis is to review our multi-institutional clinical experience involving 200 consecutive patients at 29 hospitals with confirmed COVID-19 supported with ECMO. METHODS: This analysis includes our first 200 COVID-19 patients with complete data who were supported with and separated from ECMO. These patients were cannulated between March 17 and December 1, 2020. Differences by mortality group were assessed using χ2 tests for categoric variables and Kruskal-Wallis rank sum tests and Welch's analysis of variance for continuous variables. RESULTS: Median ECMO time was 15 days (interquartile range, 9 to 28). All 200 patients have separated from ECMO: 90 patients (45%) survived and 110 patients (55%) died. Survival with venovenous ECMO was 87 of 188 patients (46.3%), whereas survival with venoarterial ECMO was 3 of 12 patients (25%). Of 90 survivors, 77 have been discharged from the hospital and 13 remain hospitalized at the ECMO-providing hospital. Survivors had lower median age (47 versus 56 years, P < .001) and shorter median time from diagnosis to ECMO cannulation (8 versus 12 days, P = .003). For the 90 survivors, adjunctive therapies on ECMO included intravenous steroids (64), remdesivir (49), convalescent plasma (43), anti-interleukin-6 receptor blockers (39), prostaglandin (33), and hydroxychloroquine (22). CONCLUSIONS: Extracorporeal membrane oxygenation facilitates survival of select critically ill patients with COVID-19. Survivors tend to be younger and have a shorter duration from diagnosis to cannulation. Substantial variation exists in drug treatment of COVID-19, but ECMO offers a reasonable rescue strategy.

Anticoagulant Use During Extracorporeal Membrane Oxygenation Using Heparin and Direct Thrombin Inhibitors in COVID-19 and ARDS Patients.

Coagulopathies develop in patients supported with the use of extracorporeal membrane oxygenation (ECMO) and can be hemorrhagic and/or thrombophilic in spite of the use of systemic anticoagulation. The purpose this study was to examine the use of heparin and direct thrombin inhibitors (DTI) in COVID-19 patients with acute respiratory distress syndrome (ARDS) on ECMO, with a subset analysis by disease state. Following IRB approval, 570 consecutive records were reviewed of adult patients on venovenous ECMO between May 2020 and December 2021. Patients were grouped by anticoagulant use: Heparin Only (n = 373), DTI Only (bivalirudin or argatroban, n = 90), or DTI after Heparin (n = 107). The effect of anticoagulant grouping was assessed using Bayesian mixed-effects logistic regression adjusting for age, body mass index (BMI), gender, days of mechanical ventilation prior to ECMO, indication for ECMO support, hepatic and renal failure, hours on ECMO, hours off anticoagulation, coagulation monitoring target, and hospital. The primary endpoint was circuit failure requiring change-out with secondary endpoints of organ failure and mortality. Regression-adjusted probability of circuit change-outs were as follows: DTI after Heparin patients-32.7%, 95% Credible Interval [16.1-51.9%]; DTI Only patients-23.3% [7.5-40.8%]; and Heparin Only patients-19.8% [8.1-31.3%]. The posterior probability of difference between groups was strongest for DTI after Heparin vs. Heparin Only (97.0%), moderate for DTI after Heparin vs. DTI Only (88.2%), and weak for DTI Only vs. Heparin only (66.6%). The occurrence of both hepatic and renal failure for DTI Only and DTI after Heparin patients was higher than that of Heparin Only patients. Unadjusted mortality was highest for DTI after Heparin (64.5%) followed by DTI Only (56.7%), and Heparin Only (50.1%, p = 0.027). DTI after Heparin was associated with an increased likelihood of circuit change-out. Unadjusted hepatic failure, renal failure, and mortality were more frequent among DTI patients than Heparin Only patients.

Zero-Balance Ultrafiltration during Cardiopulmonary Bypass Is Associated with Decreased Urine Output.

Zero-balance ultrafiltration (ZBUF) during cardiopulmonary bypass (CPB) has been purported to reduce pro-inflammatory mediators during cardiac surgery. However, its clinical benefit is equivocal and its effect on renal function unknown. The purpose of this study was to examine the effect of ZBUF on urine output in adult patients undergoing CPB. Following institutional review board approval, 98,953 records from a national registry of adult patients at 215 U.S. hospitals between January 2016 and September 2019 were reviewed. Groups were stratified according to ZBUF use. Anuric patients were excluded from the study as they were patients with missing data on urine output, ultrafiltration use, or ZBUF volume. The primary endpoint was intraoperative urine output normalized to body weight and procedure duration (total operative time). Final analysis of this endpoint was carried out using a linear mixed-effects regression model adjusting for patient and procedural characteristics, as well as practice patterns associated with surgeons and perfusionists. There was a significant 16.1% reduction in median urine output for ZBUF patients (.94 [.54, 1.47] mL/kg/h) vs. the non-ZBUF group (1.12 [.70,-1.73] mL/kg/h), p < .001. After statistically adjusting for patient and procedural characteristics, each liter of ZBUF volume was associated with an estimated change in intraoperative urine output of -.03 mL/kg/h (95% CI: [-.04 to -.02], p < .001). The median ZBUF volume was 1,550 [1,000, 2,600] mL, and when ZBUF was used, conventional ultrafiltration (CUF) was more likely to be used as well (88.4% vs. 44.8%, p < .001). ZBUF patients had median asanguineous volume and crystalloid cardioplegia nearly two times more than non-ZBUF patients, and had slightly higher red blood cell transfusions (17.6% vs. 16.3%, p < .05). The application of ZBUF during CPB was associated with patients having lower urine output and significantly higher use of CUF. Further research is required to determine if these results are reproducible in prospective clinical studies.

Multi-institutional Analysis of 100 Consecutive Patients with COVID-19 and Severe Pulmonary Compromise Treated with Extracorporeal Membrane Oxygenation: Outcomes and Trends Over Time.

The role of extracorporeal membrane oxygenation (ECMO) in the management of severely ill patients with coronavirus disease 2019 (COVID-19) continues to evolve. The purpose of this study is to review a multi-institutional clinical experience in 100 consecutive patients, at 20 hospitals, with confirmed COVID-19 supported with ECMO. This analysis includes our first 100 patients with complete data who had confirmed COVID-19 and were supported with ECMO. The first patient in the cohort was placed on ECMO on March 17, 2020. Differences by the mortality group were assessed using χ2 tests for categorical variables and Kruskal-Wallis rank-sum tests and Welch's analysis of variance for continuous variables. The median time on ECMO was 12.0 days (IQR = 8-22 days). All 100 patients have since been separated from ECMO: 50 patients survived and 50 patients died. The rate of survival with veno-venous ECMO was 49 of 96 patients (51%), whereas that with veno-arterial ECMO was 1 of 4 patients (25%). Of 50 survivors, 49 have been discharged from the hospital and 1 remains hospitalized at the ECMO-providing hospital. Survivors were generally younger, with a lower median age (47 versus 56.5 years, p = 0.014). In the 50 surviving patients, adjunctive therapies while on ECMO included intravenous steroids (26), anti-interleukin-6 receptor blockers (26), convalescent plasma (22), remdesivir (21), hydroxychloroquine (20), and prostaglandin (15). Extracorporeal membrane oxygenation may facilitate salvage and survival of selected critically ill patients with COVID-19. Survivors tend to be younger. Substantial variation exists in the drug treatment of COVID-19, but ECMO offers a reasonable rescue strategy.

Comparative Study of Bupivacaine-Fentanyl versus Ropivacaine-Fentanyl for Epidural Analgesia in Labor.

Background: Labor pain is one of the most intense pains that a woman experiences. Almost 60% of primiparous women described the pain of uterine contractions as unbearable extremely severe or excruciating. Aims: Our study aimed to relieve pain suffering of mother and to decrease fetal acidosis to make the delivery process safer for mother and baby. Settings and Design: Thus, epidural labor analgesia was designed comparing ropivacaine-fentanyl (RF) and bupivacaine-fentanyl (BF) as intermittent bolus technique. Materials and Methods: Sixty women who requested epidural analgesia having ≥3 cm cervical dilatation were allocated in two groups, one group received RF and the other group received BF. Each group received study drug 16 mL with 50 µg fentanyl and top of 10 mL and 25 µg fentanyl when visual analog scale (VAS) ≥3. The efficacy of analgesia, adverse effects, and obstetric and neonatal outcomes were compared. Statistical Analysis: For skewed data or ordered categorical data, nonparametric Mann-Whitney U-test was used for statistical analysis of two groups. For categorical data, comparisons were made by Pearson's Chi-square test or Fisher's exact test as appropriate (%). Results: Both groups were comparable in terms of demographic data and obstetric and neonatal parameters at the onset of labor Comparison of heart rate, systolic blood pressure (BP), diastolic BP, and saturation between Group RF and Group BF. It was found statistically not significant. VAS score before the epidural study drug was given, was 5 (4-5) in RF group, and was 5 (3-6) in BF group, and after 1 min, VAS score was 1 in both the groups thereafter. The score remained zero till at 100 min in both the groups till the time when the top-up dose was given. Bearing down reflex was present in all the patients as judged by the obstetrician. It was sluggish in 20% of patients in Group RF as compared to 10% in Group BF. Conclusions: From clinical and safety perspective, both RF and BF were reasonable choice for labor analgesia.

The Use of Extracorporeal Membrane Oxygenation in COVID-19 Patients with Severe Cardiorespiratory Failure: The Influence of Obesity on Outcomes.

Extracorporeal membrane oxygenation (ECMO) in the management of severely ill patients with COVID-19 has been reported in more than 5,827 cases worldwide according to the Extracorporeal Life Support Organization (ELSO). Several pre-existing conditions have been linked to an increase in COVID-19 mortality risk including obesity. The purpose of this research is to review the clinical experience from a cohort of 342 COVID-19 patients treated with ECMO in which 61.7% (211/342) are confirmed obese. Following institutional review board approval, we reviewed all 342 COVID-19 patients supported with ECMO between March 17, 2020 and March 18, 2021, at 40 American institutions from a multi-institutional database. Descriptive statistics comparing survivors to non-survivors were calculated using chi-square, Welch's ANOVA, and Kruskal-Wallis rank sum test as appropriate. Multivariable logistic regression was used to estimate the effect of body mass index (BMI) on the odds of survival while adjusting for age, gender, chronic renal failure, diabetes, asthma, hypertension, and pre-ECMO P/F ratio. Descriptive analysis showed that obese patients were more likely to be hypertensive (58.1% vs. 32%, p < .001), diabetic (42% vs. 30%, p < .05), and female (35% vs. 21%, p < .05), and had longer median days from intubation to cannulation (4.0 vs. 2.0, p < .05). Obese patients appeared to also have a slightly lower median age (47.9 vs. 50.5, p = .07), higher incidence of asthma (17.8% vs. 10.2%, p = .09), and a slightly lower pre-ECMO PaO2/FiO2 ratio (67.5 vs. 77.5, p = .08) though these differences were slightly less statistically reliable. Results from the logistic regression model suggest no statistically reliable association between BMI and odds of survival. Age had a moderately large and statistically reliable negative association with survival; the relative odds of survival for a 59-year-old patient were approximately half those of a 41-year-old patient (OR = .53, 95% CI: .36-.77, p < .001). Obesity does not seem to be a major risk factor for poor outcomes in COVID-19 patients supported with ECMO; however, age was moderately negatively associated with survival. The potential influence of other comorbidities on odds of survival among these patients warrant further investigation.

Further Studies on Triazinoindoles as Potential Novel Multitarget-Directed Anti-Alzheimer's Agents.

The inadequate clinical efficacy of the present anti-Alzheimer's disease (AD) drugs and their low impact on the progression of Alzheimer's disease in patients have revised the research focus from single targets to multitarget-directed ligands. A novel series of substituted triazinoindole derivatives were obtained by introducing various substituents on the indole ring for the development of multitarget-directed ligands as anti-AD agents. The experimental data indicated that some of these compounds exhibited significant anti-AD properties. Among them, 8-(piperidin-1-yl)-N-(6-(pyrrolidin-1-yl)hexyl)-5H-[1,2,4]triazino[5,6-b]indol-3-amine (60), the most potent cholinesterase inhibitor (AChE, IC50 value of 0.32 µM; BuChE, IC50 value of 0.21 µM), was also found to possess significant self-mediated Aß1-42 aggregation inhibitory activity (54% at 25 µM concentration). Additionally, compound 60 showed strong antioxidant activity. In the PAMPA assay, compound 60 exhibited blood-brain barrier penetrating ability. An acute toxicity study in rats demonstrated no sign of toxicity at doses up to 2000 mg/kg. Furthermore, compound 60 significantly restored the cognitive deficits in the scopolamine-induced mice model and Aß1-42-induced rat model. In the in silico ADMET prediction studies, the compound satisfied all the parameters of CNS acting drugs. These results highlighted the potential of compound 60 to be a promising multitarget-directed ligand for the development of potential anti-AD drugs.

The Effect of Antifibrinolytic Use on Intraoperative Cell Salvage: Results from a National Registry of Surgical Procedures.

Intraoperative cell salvage (ICS) is a critical component of any blood management program involving surgery with a high potential for blood loss. The introduction of antifibrinolytics (AF) may reduce blood loss. The purpose of this study was to evaluate the use of AF on ICS in non-cardiac surgical procedures. Following institutional review board approval, 69,935 consecutive case records between January 2016 and September 2019 from a national registry of adult surgical patients were reviewed. Procedure types were stratified into one of nine surgical categories: general (GN, n = 1,525), neurosurgical (NS, n = 479), obstetric (OB, n = 1,563), cervical spine (CS, n = 2,701), lumbar spine (LS, n = 38,383), hip arthroplasty (HA, n = 13,327), knee arthroplasty (KA, n = 596), vascular (VA, n = 9,845), or orthopedic other (OO, n = 1,516). The primary endpoint was the use of AF with the secondary endpoints ICS shed blood volume and volume available for return. The overall use of AF across all surgical procedures increased from 21.4% in 2016 to 25.4% in 2019. The greatest increases were seen in NS (4.4% to 16.2%), LS (13.7% to 23.1%), and HA (55.8% to 61.9%). For several procedure types, there was an initial increase then either a leveling off or a decline in AF use: OB initially increased from 6.2% to 10.8% in 2018, whereas GN (9.4% to 7.2%) and VA surgery declined slightly (9.9% to 5.7%). When comparing patients who did not receive AF with those who did, there were similar volumes of ICS available for return in all groups, except for LS, GN, and VA, where lower volumes were seen in the No-AF groups. The use of AF has increased each year over the 4-year period in most of the surgical categories, but several have declined. There may be a beneficial effect of AF with lower ICS volumes available for return in a few groups.

Novel carbazole-stilbene hybrids as multifunctional anti-Alzheimer agents.

Molecules capable of engaging with multiple targets associated with pathological condition of Alzheimer's disease have proved to be potential anti-Alzheimer's agents. In our goal to develop multitarget-directed ligands for the treatment of Alzheimer's disease, a novel series of carbazole-based stilbene derivatives were designed by the fusion of carbazole ring with stilbene scaffold. The designed compounds were synthesized and evaluated for their anti-AD activities including cholinesterase inhibition, Aß aggregation inhibition, antioxidant and metal chelation properties. Amongst them, (E)-1-(4-(2-(9-ethyl-9H-carbazol-3-yl)vinyl)phenyl)-3-(2-(pyrrolidin-1-yl)ethyl)thiourea (50) appeared to be the best candidate with good inhibitory activities against AChE (IC50 value of 2.64 µM) and BuChE (IC50 value of 1.29 µM), and significant inhibition of self-mediated Aß1-42 aggregation (51.29% at 25 µM concentration). The metal chelation study showed that compound (50) possessed specific copper ion chelating property. Additionally, compound (50) exhibited moderate antioxidant activity. To understand the binding mode of 50, molecular docking studies were performed, and the results indicated strong non-covalent interactions of 50 with the enzymes in the active sites of AChE, BuChE as well as of the Aß1-42 peptide. Additionally, it showed promising in silico ADMET properties. Putting together, these findings evidently showed compound (50) as a potential multitarget-directed ligand in the course of developing novel anti-AD drugs.

Strengthening antioxidant defense & cardio protection by Piper betle: An in-vitro study.

INTRODUCTION: The purpose of this research work was to evaluate Piper betle ethyl acetate extract (PBEA) for its free radical scavenging, antioxidant, anti-apoptotic activities and its role in protecting against oxidative cardiac cell injury. METHODS: The Free radical scavenging activity and antioxidant potential of PBEA were evaluated using various non-cellular methods (1,1-Diphenyl-2-picrylhydrazyl, ß-carotene bleaching, superoxide anion, hydroxyl radical, hydrogen peroxide, Reducing power, Total phenolics and Total flavonoids). PBEA was standardized with Eugenol by GC-FID analysis. Furthermore, PBEA was also assessed for its cytotoprotective effect against 100µM H2O2 in H9c2 cells using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay. Intracellular reactive oxygen species scavenging and anti-apoptoic activity of PBEA was assessed by using 2', 7'-Dichlorofluorescein diacetate and Annexin- Propidium Iodide, respectively. RESULTS: PBEA exhibited radical scavenging and antioxidant defense response at different magnitudes of potency. Eugenol, a cardiac protective bioactive molecule in PBEA was found to be 43.43 ± 1.46 mg/g of PBEA extract. Further, pre-incubation of H9c2 cells with 10 µg/ml PBEA for 24 h exhibited remarkable cytoprotective effect against H2O2 induced oxidative stress. PBEA at 10 µg/ml dose with 24 h contact with H9c2 cells significantly enhanced the activity of cellular defense system and significantly decreased intracellular ROS (P < 0.001) and apoptosis (P < 0.01) thereby protecting against the cytotoxic effects of H2O2. CONCLUSION: These outcomes indicated that PBEA could shield against oxidative and apoptotic cardiac cell injury in invitro studies. Thus, PBEA might be a desirable antioxidant of natural origin that has future clinical implications in both health care and food industry.

Facile synthesis of stable selenocystine peptides and their solution state NMR studies.

A facile general route for the synthesis of various selenocystine tripeptides containing acidic, basic and neutral side chain amino acids is reported. Here, TFA labile side chain protected selenocysteine has been used as a precursor for the synthesis of selenopeptides. The peptides are highly stable in dimethyl sulphoxide, thus enabling detailed NMR studies by solution phase 1- and 2-dimensional NMR spectroscopy.

Novel Multitarget Directed Triazinoindole Derivatives as Anti-Alzheimer Agents.

The multifaceted nature of Alzheimer's disease (AD) demands treatment with multitarget-directed ligands (MTDLs) to confront the key pathological aberrations. A novel series of triazinoindole derivatives were designed and synthesized. In vitro studies revealed that all the compounds showed moderate to good anticholinesterase activity; the most active compound 23e showed an IC50 value of 0.56 ± 0.02 µM for AChE and an IC50 value of 1.17 ± 0.09 µM for BuChE. These derivatives are also endowed with potent antioxidant activity. To understand the plausible binding mode of the compound 23e, molecular docking studies and molecular dynamics simulation studies were performed, and the results indicated significant interactions of 23e within the active sites of AChE as well as BuChE. Compound 23e successfully diminished H2O2-induced oxidative stress in SH-SY5Y cells and displayed excellent neuroprotective activity against H2O2 as well as Aß-induced toxicity in SH-SY5Y cells in a concentration dependent manner. Furthermore, it did not show any significant toxicity in neuronal SH-SY5Y cells in the cytotoxicity assay. Compound 23e did not show any acute toxicity in rats at doses up to 2000 mg/kg, and it significantly reversed scopolamine-induced memory deficit in mice model. Additionally, compound 23e showed notable in silico ADMET properties. Taken collectively, these findings project compound 23e as a potential balanced MTDL in the evolution process of novel anti-AD drugs.