Simulation in Perioperative Liver Transplant Anesthesia: A Systematic Review.

Due to the complexity of liver transplant patients and the variability in exposure to transplantation by anesthesia trainees, simulation is often required as an adjunct to clinical experience. This systematic review identifies current simulation models in the literature that pertain to perioperative liver transplant anesthesia. Data were collected by performing an electronic search of the PubMed and Scopus databases for articles describing simulation in transplant anesthesia. Abstracts were screened using the preferred reporting items for systematic reviews and meta-analysis (PRISMA) guidelines. Three reviewers analyzed 16 abstracts found in the search and agreed upon articles that met the inclusion criteria for the systematic review. A total of five publications met the inclusion criteria; they could be grouped as cognitive skills and technical skills simulators. Cognitive skills simulators utilized high-fidelity mannequins and animal models combined with traditional educational material to enhance pattern recognition of critical complications during liver transplantation. One manuscript focused on a technical skills acquisition by utilizing transesophageal echocardiography (TEE) to identify intraoperative pathologies. There is a heterogeneity in the exposure to liver transplant care during anesthesia training. Simulation provides low-stakes exposure to the high-stakes skills required in the operating room. Hence, it can be used as an adjunct to improve both cognitive and technical skill acquisition for perioperative transplant anesthesia. The goal of these simulation programs is to improve patient outcomes and produce more capable anesthesiologists.

Impact of climate change on river water temperature and dissolved oxygen: Indian riverine thermal regimes.

The impact of climate change on the oxygen saturation content of the world's surface waters is a significant topic for future water quality in a warming environment. While increasing river water temperatures (RWTs) with climate change signals have been the subject of several recent research, how climate change affects Dissolved Oxygen (DO) saturation levels have not been intensively studied. This study examined the direct effect of rising RWTs on saturated DO concentrations. For this, a hybrid deep learning model using Long Short-Term Memory integrated with k-nearest neighbor bootstrap resampling algorithm is developed for RWT prediction addressing sparse spatiotemporal RWT data for seven major polluted river catchments of India at a monthly scale. The summer RWT increase for Tunga-Bhadra, Sabarmati, Musi, Ganga, and Narmada basins are predicted as 3.1, 3.8, 5.8, 7.3, 7.8 °C, respectively, for 2071-2100 with ensemble of NASA Earth Exchange Global Daily Downscaled Projections of air temperature with Representative Concentration Pathway 8.5 scenario. The RWT increases up to7 °C for summer, reaching close to 35 °C, and decreases DO saturation capacity by 2-12% for 2071-2100. Overall, for every 1 °C RWT increase, there will be about 2.3% decrease in DO saturation level concentrations over Indian catchments under climate signals.

Cross-Sectional Study of Osteopathic General Surgeons in University-Based General Surgery Departments.

INTRODUCTION: Discrepancy between osteopathic (DO) and allopathic (MD) graduates in general surgery spans across all levels of training. In this cross-sectional study, we characterized DO surgeons who serve as faculty at university-based general surgery departments. METHODS: Overall, 106 university-based surgery departments were reviewed. DO and MD surgeons from the same institutions were identified, and demographic data were tabulated. MD surgeons were the control group. Univariate analysis and multivariate regression models were used to compare total publications, h-index, and citations. RESULTS: A total of 70 DO surgeons from 34 institutions were identified: 53 assistant professors, 16 associate professors, and one full professor. Of the DO surgeons, 35.7% completed residency at a university-based program, and 92.9% completed a fellowship, with surgical critical care and trauma being the most common. They were compared to 1,307 MD surgeons from the same institutions. Univariate analysis showed that MD faculty graduated medical school earlier (mean years (standard deviation (SD)): 14.8 (6.0) versus 23.3 (10.6); p<0.0001), had more total publications (median (interquartile range (IQR)): 5 (2.0-18.3) versus 35 (15.0-79.0); p<0.0001), had higher number of citations (median (IQR): 61.0 (14.0-265.0) versus 655.0 (155.0-2267.0); p<0.001), and had a higher h-index (median (IQR): 3 (1.0-8.0) versus 12 (6.0-24.0); p<0.001). Negative binomial regression models accounting for years since graduation, gender, and degree were performed. At the assistant professor rank, MD surgeons had more total publications (exponential coefficient (CI): 2.24 (1.67-3.02); p<0.001), more citations (3.10 (2.20-4.11); p<0.001), and a higher h-index (1.93 (1.36-2.73); p<0.001). Similar trends were noted at the associate professor level with MD surgeons having more total publication (1.67 (1.00-2.79); p=0.049), more citations (3.63 (2.13-6.18); p<0.001), and higher h-index (1.93 (1.10-3.39); p=0.022). CONCLUSIONS: To address this discrepancy between DO and MD faculty surgeons, action must begin at the medical school and continue through residency. DO trainees need better access to mentorship and research support to foster an academic career.

Assessment of genetic determinants of the association of γ' fibrinogen in relation to cardiovascular disease.

OBJECTIVE: γ' fibrinogen is a newly emerging biomarker that is associated with cardiovascular disease (CVD). However, the genetic determinants of γ' fibrinogen levels are unknown. We therefore conducted a genome-wide association study on 3042 participants from the Framingham Heart Study Offspring Cohort. METHODS AND RESULTS: A genome-wide association study with 2.5 million single-nucleotide polymorphisms (SNPs) was carried out for γ' fibrinogen levels from the cycle 7 examination. Fifty-four SNPs in or near the fibrinogen gene locus demonstrated genome-wide significance (P<5.0×10(-8)) for association with γ' fibrinogen levels. The top-signal SNP was rs7681423 (P=9.97×10(-110)) in the fibrinogen gene locus near FGG, which encodes the γ chain. Conditional on the top SNP, the only other SNP that remained genome-wide significant was rs1049636. Associations between SNPs, γ' fibrinogen levels, and prevalent CVD events were examined using multiple logistic regression. γ' fibrinogen levels were associated with prevalent CVD (P=0.02), although the top 2 SNPs associated with γ' fibrinogen levels were not associated with CVD. These findings contrast those for total fibrinogen levels, which are associated with different genetic loci, particularly FGB, which encodes the Bß chain. CONCLUSIONS: γ' fibrinogen is associated with prevalent CVD and with SNPs exclusively in and near the fibrinogen gene locus.

Gamma' fibrinogen: evaluation of a new assay for study of associations with cardiovascular disease.

BACKGROUND: Studies of disease associations with gamma' fibrinogen, a newly emerging risk factor for cardiovascular disease, have been hampered by the lack of a standardized and well-characterized assay. METHODS: We developed an immunometric technique to measure gamma' fibrinogen concentrations in plasma and studied the clinical utility of this test in samples from healthy individuals enrolled in the Framingham Offspring Study and in a separate case/control study of coronary artery disease (CAD). Monoclonal antibody 2.G2.H9, specific for the unique carboxyl terminal peptide of the fibrinogen gamma' chain, was used as capture antibody. Sheep antihuman fibrinogen/horseradish peroxidase conjugate was used for detection, with 3,3',5,5'-tetramethylbenzidine as substrate. We evaluated the linearity, imprecision, analytical specificity, and lower limit of quantification of the assay. We determined the reference interval for gamma' fibrinogen in healthy individuals from the Framingham Offspring Study (n = 2879) and quantified associations between gamma' fibrinogen and cardiovascular disease risk factors. The sensitivity and specificity of gamma' fibrinogen in evaluating CAD patients (n = 133) was determined with ROC curve analysis. RESULTS: The gamma' fibrinogen ELISA had within-run CVs of 13.4% at 0.127 g/L and 4.8% at 0.416 g/L. The limit of quantification at an imprecision of 20% was 0.10 g/L. The reference interval for healthy individuals was 0.088-0.551 g/L. ROC curve analysis of results from patients with CAD yielded an area under the curve of 0.76, with a diagnostic accuracy of 0.78 at a decision threshold of 0.30 g/L. CONCLUSIONS: gamma' Fibrinogen shows excellent utility for cardiovascular risk analysis.

Anxiolytic effect of midazolam premedication assessed by clinical and platelet aggregation profiles.

BACKGROUND: It is well documented that surgery is associated with increased anxiety, which has an adverse impact on patient's outcome. This study was designed to assess the anxiolytic effect of midazolam in pre-anaesthetic medication by using clinical and platelet aggregation profiles. METHODS: Sixty ASA I and II female patients aged between 35 and 60 years undergoing elective abdominal hysterectomy were randomly divided into two equal groups. Group I received placebo as pre-medication while group II received 0.15 mg/kg midazolam as pre-medication 1 hour preoperatively. They were monitored for visual analogue scale (VAS) for anxiety, observer's anxiety criteria, sedation score, blood pressure, heart rate and platelet aggregation profile immediately before and 1 hour after pre-medication. RESULTS: There was statistically significant difference with respect to VAS of anxiety, observer's anxiety criteria, sedation scores, systolic and diastolic blood pressure (p<0.05). Heart rate was higher in the midazolam group but this was not statistically significant. There was no statistical significant difference in platelet aggregation profile in the two groups. CONCLUSION: Findings of the study suggest midazolam is a good anxiolytic for pre-medication and its effect on platelet aggregation profile needs to be further evaluated.

An imprecise fuzzy risk approach for water quality management of a river system.

Uncertainty plays an important role in water quality management problems. The major sources of uncertainty in a water quality management problem are the random nature of hydrologic variables and imprecision (fuzziness) associated with goals of the dischargers and pollution control agencies (PCA). Many Waste Load Allocation (WLA) problems are solved by considering these two sources of uncertainty. Apart from randomness and fuzziness, missing data in the time series of a hydrologic variable may result in additional uncertainty due to partial ignorance. These uncertainties render the input parameters as imprecise parameters in water quality decision making. In this paper an Imprecise Fuzzy Waste Load Allocation Model (IFWLAM) is developed for water quality management of a river system subject to uncertainty arising from partial ignorance. In a WLA problem, both randomness and imprecision can be addressed simultaneously by fuzzy risk of low water quality. A methodology is developed for the computation of imprecise fuzzy risk of low water quality, when the parameters are characterized by uncertainty due to partial ignorance. A Monte-Carlo simulation is performed to evaluate the imprecise fuzzy risk of low water quality by considering the input variables as imprecise. Fuzzy multiobjective optimization is used to formulate the multiobjective model. The model developed is based on a fuzzy multiobjective optimization problem with max-min as the operator. This usually does not result in a unique solution but gives multiple solutions. Two optimization models are developed to capture all the decision alternatives or multiple solutions. The objective of the two optimization models is to obtain a range of fractional removal levels for the dischargers, such that the resultant fuzzy risk will be within acceptable limits. Specification of a range for fractional removal levels enhances flexibility in decision making. The methodology is demonstrated with a case study of the Tunga-Bhadra river system in India.

gammaA/gamma' fibrinogen inhibits thrombin-induced platelet aggregation.

The minor gammaA/gamma' fibrinogen isoform contains a high affinity binding site for thrombin exosite II that is lacking in the major gammaA/gammaA fibrinogen isoform. We therefore investigated the biological consequences of the gamma' chain binding to thrombin. Thrombin-induced platelet aggregation was inhibited by gammaA/gamma' fibrinogen. Carboxyl terminal peptide fragment gamma'410-427 from the gamma' chain was also inhibitory, with an IC(50) of approximately 200 microM in whole plasma. Deletion of the peptide from either the amino or carboxyl end significantly decreased inhibition. In contrast to thrombin-induced platelet aggregation, aggregation induced by epinephrine, ADP, arachidonic acid, or SFLLRN peptide showed little inhibition by the gamma' peptide. The inhibition of thrombin-induced platelet aggregation was not due to direct inhibition of the thrombin active site, since cleavage of a small peptidyl substrate was 91% of normal even in the presence of 1 mM gamma'410-427. The gamma'410-427 peptide blocked platelet adhesion to immobilized thrombin under both static and flow conditions, blocked soluble thrombin binding to platelet GPIbalpha, and inhibited PAR1 cleavage by thrombin. These results suggest that the gamma' chain of fibrinogen inhibits thrombin-induced platelet aggregation by binding to thrombin exosite II. Thrombin that is bound to the gamma' chain is thereby prevented from activating platelets, while retaining its amidolytic activity.

Fibrinogen Hershey IV: a novel dysfibrinogen with a gammaV411I mutation in the integrin alpha(IIb)beta(3) binding site.

The carboxyl terminal segment of the fibrinogen gamma chain from gamma408-411 plays a crucial role in platelet aggregation via interactions with the platelet receptor alpha(IIb)beta(3). We describe here the first naturally-occurring fibrinogen point mutation affecting this region and demonstrate its effects on platelet interactions. DNA sequencing was used to sequence the proband DNA, and platelet aggregation and direct binding assays were used to quantitate the biological effects of fibrinogen Hershey IV. The Hershey IV proband was found to be heterozygous for two mutations, gammaV411I and gammaR275C. Little difference in aggregation was seen when fibrinogen Hershey IV was compared to normal fibrinogen. However, less aggregation inhibition was observed using a competing synthetic dodecapeptide containing the V411I mutation as compared to the wild-type dodecapeptide. Purified fibrinogen Hershey IV also bound to purified platelet alpha(IIb)beta(3) with a lower affinity than wild-type fibrinogen. These findings show that the gammaV411I mutation results in a decreased ability to bind platelets. In the heterozygous state, however, the available wild-type fibrinogen appears to be sufficient to support normal platelet aggregation.

Fibrinogen gamma' chain carboxy terminal peptide selectively inhibits the intrinsic coagulation pathway.

The minor gammaA/gamma' isoform of fibrinogen contains a high affinity binding site for thrombin exosite II that is lacking in the major fibrinogen isoform, gammaA/gammaA fibrinogen. The biological consequences of gamma' chain binding to thrombin were therefore investigated. Coagulation assays, thrombin activity assays, and a primate thrombosis model were used to characterize the biological effects of the gamma' 410-427 peptide. The gamma' peptide had little effect on thrombin cleavage of the small peptidyl substrate tosyl-glycyl-prolyl-arginine-4-nitranilide acetate. However, in vitro assays demonstrated that the gamma' peptide inhibited thrombin cleavage of larger proteinaceous substrates, including fibrinogen and factor VIII. The gamma' peptide inhibited the activated partial thromboplastin time in plasma and showed greater inhibition of activated partial thromboplastin time assays than prothrombin time assays, consistent with the inhibition of factor VIII cleavage. Studies in a baboon thrombosis model showed that the gamma' 410-427 peptide inhibited fibrin-rich thrombus formation (typical of venous thrombi) and, to a lesser extent, platelet-rich thrombus formation (typical of arterial thrombi). These results indicate that binding of thrombin exosite II by the gamma' peptide has selective effects on the intrinsic pathway.

General anaesthesia for emergency caesarian section in a patient with Eisenmenger's syndrome and pre-eclampsia.

Pregnancy is poorly tolerated in patients with Eisenmenger syndrome (ES) with maternal mortality of 30-50%. Physiological changes of pregnancy decreases systemic vascular resistance that further aggravates the bi-directional or right to left shunt associated with ES. When it occurs with eclampsia, the morbidity and mortality are even higher. We report a case of 30 weeks pregnant woman with ES, who underwent emergency caesarian section because of pre-eclampsia. The intra-operative course was uneventful but she died on the second post-operative day. Post-operatively she was managed by the cardiologist in the coronary care unit. The probable cause being that she was over transfused, as the fluid status was not assessed by any invasive monitoring (like CVP). It was concluded that patients should be monitored closely in the post-operative period in the intensive care unit with complete invasive monitoring for up to a week to prevent factors resulting in worsening of the shunt (such as fluid balance) and thromboembolic phenomenon.

Molecular characterization of marker-free transgenic lines of indica rice that accumulate carotenoids in seed endosperm.

A single Agrobacterium strain harbouring two binary plasmids was successfully used for the first time to develop a marker-free transgenic rice of improved nutritional value. Sixty-eight T0 co-transformants were obtained in three indica rice cultivars--two popular high-yielding Bangladeshi varieties (BR28 and BR29), and one high-iron rice cultivar (IR68144). Marker-free lines were obtained from 14 out of 24 selected co-transformants screened in the T1 generation. The accumulation of total carotenoids in polished T2 rice seeds of the primary transgenic VPBR29-17-37 reached levels of up to 3.0 microg/g, with the level of beta-carotene reaching 1.8 microg/g. In the cultivars BR28 and IR68144, total carotenoid levels in the transformants reached 2.0 microg/g of polished rice seeds. The levels of lutein and other carotenoids in the seeds were also significantly enhanced. T1 plants obtained from primary transgenics with simple gene-integration patterns tended to have a lower carotenoid content than the original parental lines. This study describes the development of marker-free transgenic rice lines containing high levels of carotenoids, and addresses the relationship between the rearrangement of transgenes and the presence of metabolic end products in transgenic rice.

Evaluation of cardiology consultations sought from the anaesthesia clinic.

OBJECTIVE: To evaluate the criteria for cardiology referrals and to assess the perioperative relevance of the cardiology advice given in patients evaluated for non-cardiac surgery. DESIGN: Single center, observational study. PLACE AND DURATION OF STUDY: Outpatient Anaesthesia Clinic at The Aga Khan University Hospital (AKUH), between January 2001- August 2001 and February 2002- August 2002. MATERIALS AND METHODS: A review of case files of 70 patients, scheduled for non-cardiac surgery, who were referred for cardiology consultations from the anaesthesia clinic at AKUH during the study period. The clinical criteria for seeking cardiology advice, the cardiology advice given, its influence on patient management, as well as number of adverse cardiac events in the perioperative period were documented. RESULTS: A history of hypertension, ischemic heart disease, and ECG abnormalities were the major criteria for seeking opinion on cardiac status. Cardiology advice frequently resulted in the ordering of extensive cardiac investigations. Among the patients identified for further tests by the cardiologists, 75% had no evidence of ischemic heart disease or myocardial dysfunction; none of them were monitored invasively intraoperatively or had adverse cardiac events in the perioperative period requiring intensive care or prolonged hospital stay. CONCLUSION: No definite criteria or pattern for referrals was identified. Most of the referrals did not fall within the AHA guidelines. Cardiology advice given had very little influence on the perioperative management.

Is there a role of a small dose of propofol in the treatment of laryngeal spasm?

BACKGROUND: Propofol has been found to depress the laryngeal reflexes. We studied whether this property could be utilized to relieve laryngeal spasm. METHODS: This study was conducted over a period of 3 years, and included children aged 3-10 years, ASA status I and II. Most of the children were undergoing minor surgical procedures, under general anaesthesia with Laryngeal Mask Airway (LMA trade mark ) and caudal epidural analgesia. RESULTS: During this period, 20 patients developed laryngeal spasm on removal of the LMA at the end of surgery. Initially, they all were treated with 100% O2, with gentle positive pressure ventilation. Out of 20 patients, seven responded well with 100% O2 and gentle positive pressure ventilation. The remaining 13 were treated with a small dose of propofol (0.8 mg.kg-1 body weight). Laryngeal spasm was relieved successfully in 10 patients and three patients required intubation to improve their oxygenation. CONCLUSIONS: Propofol in a small dose (0.8 mg.kg-1 body weight) was a useful drug to relieve laryngeal spasm in most children (76.9%) following the removal of the LMA. Because it was not found to be effective in all patients, succinylcholine still has a role to play in critical conditions. However, we recommend propofol as a suitable alternative for relieving laryngeal spasm in situations where succinylcholine is contraindicated.

Association of gammaA/gamma' fibrinogen levels and coronary artery disease.

GammaA/gamma' fibrinogen is a fibrinogen isoform that constitutes about 15% of total plasma fibrinogen. This isoform contains an additional binding site for zymogen factor XIII and for active thrombin, and forms fibrin clots that are resistant to fibrinolysis in vitro. Little is known about the variability of gammaA/gamma' fibrinogen levels in human populations, whereas total fibrinogen levels are known to increase with age and are higher in women than in men. In this report, evidence is presented that, in contrast to total fibrinogen levels, gammaA/gamma' fibrinogen levels showed no significant association with age or gender in a population of normal blood donors. A study of gammaA/gamma' fibrinogen levels in patients undergoing coronary angiography also showed that gammaA/gamma' fibrinogen levels were higher on average in coronary artery disease patients than in patients without coronary artery disease, and that this association was independent of total fibrinogen levels.

Effect of route of buprenorphine on recovery and postoperative analgesic requirement in paediatric patients.

BACKGROUND: We compared the effects of extradural with intravenous (i.v.) buprenorphine on postoperative pain and recovery characteristics. METHODS: Thirty patients, aged 11-13 years, who were undergoing inguinal hernia repair with or without orchidopexy, were randomly allocated to receive either caudal 0.5% bupivacaine alone (group A) or were additionally given i.v. buprenorphine 2.5 micro g.kg-1 (group B) or caudal buprenorphine in the same dose (group C). Patients were followed for 8 h after the end of surgery. RESULTS: All patients remained haemodynamically stable during the study period and no clinical respiratory depression was seen. Nausea, vomiting, urinary retention and pruritus were more common in the extradural buprenorphine group. Three patients in group A, five in group B and eight in group C did not require any additional analgesia during the study period. The incidence of vomiting was 20%, 50% and 80% in groups A, B and C, respectively. Four patients in group C had urinary retention compared with one each in the other two groups. CONCLUSIONS: Administration of buprenorphine resulted in a higher incidence of side-effects.