Rupture Risk of Intracranial Aneurysm and Prediction of Hemorrhagic Stroke after Liver Transplant.

Postoperative hemorrhagic stroke (HS) is a rare yet devastating complication after liver transplantation (LT). Unruptured intracranial aneurysm (UIA) may contribute to HS; however, related data are limited. We investigated UIA prevalence and aneurysmal subarachnoid hemorrhage (SAH) and HS incidence post-LT. We identified risk factors for 1-year HS and constructed a prediction model. This study included 3544 patients who underwent LT from January 2008 to February 2019. Primary outcomes were incidence of SAH, HS, and mortality within 1-year post-LT. Propensity score matching (PSM) analysis and Cox proportional hazard analysis were performed. The prevalence of UIAs was 4.63% (n = 164; 95% confidence interval (CI), 3.95-5.39%). The 1-year SAH incidence was 0.68% (95% CI, 0.02-3.79%) in patients with UIA. SAH and HS incidence and mortality were not different between those with and without UIA before and after PSM. Cirrhosis severity, thrombocytopenia, inflammation, and history of SAH were identified as risk factors for 1-year HS. UIA presence was not a risk factor for SAH, HS, or mortality in cirrhotic patients post-LT. Given the fatal impact of HS, a simple scoring system was constructed to predict 1-year HS risk. These results enable clinical risk stratification of LT recipients with UIA and help assess perioperative HS risk before LT.

Prognostic Value of B-Type Natriuretic Peptide in Liver Transplant Patients: Implication in Posttransplant Mortality.

BACKGROUND AND AIMS: Despite frequent cirrhotic cardiomyopathy or subclinical heart failure (HF), the prognostic value of peri-liver transplant (LT) B-type natriuretic peptide (BNP) has been poorly studied in advanced liver disease. We examined the association between BNP and mortality in a large cohort of LT patients and identified risk factors for peri-LT BNP increase. APPROACH AND RESULTS: Using prospectively collected data from the Asan LT Registry between 2008 and 2019, 3,811 patients who measured serial pretransplant BNP (preBNP) and peak BNP levels within the first 3 posttransplant days (postBNPPOD3 ) were analyzed. Thirty-day all-cause mortality predicted by adding preBNP and/or postBNPPOD3 to the traditional Revised Cardiac Risk Index (RCRI) was evaluated. PreBNP > 400 pg/mL (known cutoff of acute HF) was found in 298 (7.8%); however, postBNPPOD3  > 400 pg/mL was identified in 961 (25.2%) patients, specifically in 40.4% (531/1,315) of those with a Model for End-Liver Disease score (MELDs) > 20. Strong predictors of postBNPPOD3  > 400 pg/mL were preBNP, hyponatremia, and MELDs, whereas those of preBNP > 400 pg/mL were MELDs, kidney failure, and respiratory failure. Among 100 (2.6%) post-LT patients who died within 30 days, patients with postBNPPOD3  ≤ 150 pg/mL (43.1%, reference group), 150-400 pg/mL (31.7%), 400-1,000 pg/mL (18.5%), 1,000-2,000 pg/mL (4.7%), and >2,000 pg/mL (2.0%) had 30-day mortalities of 0.9%, 2.2%, 4.0%, 7.7%, and 22.4%, respectively. Adding preBNP, postBNPPOD3 , and both BNP to RCRI improved net reclassification index to 22.5%, 29.5%, and 33.1% of 30-day mortality, respectively. CONCLUSIONS: PostBNPPOD3  > 400 pg/mL after LT was markedly prevalent in advanced liver disease and mainly linked to elevated preBNP. Routine monitoring of peri-LT BNP provides incremental prognostic information; therefore, it could help risk stratification for mortality as a practical and useful biomarker in LT.

Recurrent thrombosis after carotid endarterectomy secondary to activated protein C resistance and essential thrombocytosis: A case report.

RATIONALE: Thrombosis is a major cause of morbidity in the perioperative period. Although many risk factors are known, activated protein C resistance is a prominent risk for thrombosis. Activated protein C resistance frequently occurs with recurrent thromboembolism. PATIENT CONCERNS: A 59-year-old Korean woman patient with hypertension was admitted due to dysarthria and left side motor weakness. DIAGNOSIS AND INTERVENTIONS: Magnetic resonance imaging showed subacute cerebral infarction with right frontoparietal lobe and stenosis at the right internal carotid artery. She underwent right carotid endarterectomy under general anesthesia. However, recurrent thrombosis on postoperative day 1 was noted at patient's right carotid artery, which prompted emergency surgery. Additional preoperative laboratory review revealed findings for activated protein C resistance, low protein S activity, antinuclear antibody (>1:160), anti-cardiolipin IgM antibody (16.6), and thrombocytosis, Janus kinase and factor V Leiden mutations. At the intensive care unit, heparin was continually infused until postoperative day 12 and was then switched to warfarin. OUTCOMES: Patient was discharged at postoperative day 21 without any event. Patient had no signs of recurrence within the 3-year follow-up period, and she is still on oral warfarin and clopidogrel. LESSONS: Screening test for hypercoagulability can be used to identify patients at higher risk of postoperative complications. If hypercoagulability state is confirmed by laboratory testing, a suitable anticoagulant treatment plan should be made within the perioperative period.

Change of QT variability index during general anesthesia.

BACKGROUND: The QT variability index (QTVI)-a non-invasive measure of beat-to-beat QT interval (QTI) fluctuations-is related to myocardial repolarization lability. The QTVI represents the relationship between QTI and the RR interval. Elevated QTVI is associated with an increased risk of malignant ventricular arrhythmias and sudden death. We investigated the influence of general anesthesia and tourniquets on the QTVI. METHODS: We studied fifty patients who received total knee replacement arthroplasty under sevoflurane anesthesia. We measured QTI, corrected QTI (QTc), T-wave peak-to-end interval (TPE), QTVI, and heart rate variability. All variables were calculated at baseline (B), 30 min after general anesthesia (A), 30 min (TQ1) and 60 min (TQ2) after tourniquet inflation, and at tourniquet deflation (TQR). RESULTS: Prolongation of QTI was detected at all times, and QTc was significantly prolonged TQR. TPE was unchanged during general anesthesia. The QTVI was significantly decreased and more negative during anesthesia and tourniquet inflation. After deflation of the tourniquet, the QTVI was restored to preanesthetic values. Low frequency (LF) was significantly decreased during general anesthesia, but high frequency (HF) was somewhat maintained, except at TQ2. The LF/HF ratio was significantly decreased at A and TQ2. CONCLUSIONS: Sevoflurane based general anesthesia induced repolarization stability and, more negativity of the QTVI, in patients undergoing total knee replacement arthroplasty.

Tristetraprolin suppresses the EMT through the down-regulation of Twist1 and Snail1 in cancer cells.

Inhibition of epithelial-mesenchymal transition (EMT)-inducing transcription factors Twist and Snail prevents tumor metastasis but enhances metastatic growth. Here, we report an unexpected role of a tumor suppressor tristetraprolin (TTP) in inhibiting Twist and Snail without enhancing cellular proliferation. TTP bound to the AU-rich element (ARE) within the mRNA 3'UTRs of Twist1 and Snail1, enhanced the decay of their mRNAs and inhibited the EMT of cancer cells. The ectopic expression of Twist1 or Snail1 without their 3'UTRs blocked the inhibitory effects of TTP on the EMT. We also observed that TTP overexpression suppressed the growth of cancer cells. Our data propose a new model whereby TTP down-regulates Twist1 and Snail1 and inhibits both the EMT and the proliferation of cancer cells.

General anesthesia in a patient with multicentric Castleman's disease: a case report.

Castleman's disease (CD) is a rare lymphoproliferative disorder of undetermined etiology. Unicentric Castleman's disease is confined to a single lymph node; it is usually asymptomatic though sometimes has local manifestations related to mass effects. In contrast, multicentric Castleman's disease (MCD) typically presents with lymphoid hyperplasia at multiple sites; it is associated with systemic symptoms and abnormal laboratory findings, with a less favorable prognosis. In case of anesthesia in CD, an exhaustive preanesthetic evaluation is essential to identify associated clinical manifestations which may influence the management of the anesthesia. Perioperative careful monitoring and proper anesthetic management are both important. We report a case of general anesthesia with anesthetic management in a patient with MCD that has not been documented in the literature.

Alteration of the QT variability index in end-stage liver disease.

BACKGROUND: A prolonged QT interval can lead to malignant ventricular arrhythmias and sudden cardiac death, and has frequently been found in end-stage liver disease (ESLD). However, myocardial repolarization lability has not yet been fully investigated. We evaluated the QT variability index (QTVI), a marker of temporal inhomogeneity in ventricular repolarization and an abnormality associated with re-entrant malignant ventricular arrhythmias. We determined whether QTVI is affected by the head-up tilt test in ESLD. METHODS: We assessed 36 ESLD patients and 12 control subjects without overt heart disease before and after the 70-degree head-up tilt test. The electrocardiography signal (lead II) was recorded on a computer with an analog-to-digital converter. The RR interval (RRI) and QT interval were measured after recording 5 min of the digitized electrocardiography. Then, the QT intervals were corrected with Bazett's formula (QTc). QTVI was calculated through the following formula: QTVI = log10 [(QTv/QTm2)/(RRIv/RRIm2)], QTv/RRIv: variance of QTI/RRI, QTm/RRIm: mean of QT interval/RRI. RESULTS: Cirrhotic patients exhibited an elevated QTVI. In particular, Child class C patients had a significantly increased QTVI compared to Child class A patients and the control subjects in the supine position. However, the head-up tilt test did not cause a significant difference in QTVI in relation to the severity of ESLD. CONCLUSIONS: Myocardial repolarization lability was significantly altered in end-stage liver disease. Our data suggest that the severity of ESLD is associated with the degree of the alteration in the QT variability index.

Ethanol production from galactose by a newly isolated Saccharomyces cerevisiae KL17.

A wild-type yeast strain with a good galactose-utilization efficiency was newly isolated from the soil, and identified and named Saccharomyces cerevisiae KL17 by 18s RNA sequencing. Its performance of producing ethanol from galactose was investigated in flask cultures with media containing various combination and concentrations of galactose and glucose. When the initial galactose concentration was 20 g/L, it showed 2.2 g/L/h of substrate consumption rate and 0.63 g/L/h of ethanol productivity. Although they were about 70 % of those with glucose, such performance of S. cerevisiae KL17 with galactose was considered to be quite high compared with other strains reported to date. Its additional merit was that its galactose metabolism was not repressed by the existence of glucose. Its capability of ethanol production under a high ethanol concentration was demonstrated by fed-batch fermentation in a bioreactor. A high ethanol productivity of 3.03 g/L/h was obtained with an ethanol concentration and yield of 95 and 0.39 g/L, respectively, when the cells were pre-cultured on glucose. When the cells were pre-cultured on galactose instead of glucose, fermentation time could be reduced significantly, resulting in an improved ethanol productivity of 3.46 g/L/h. The inhibitory effects of two major impurities in a crude galactose solution obtained from acid hydrolysis of galactan were assessed. Only 5-Hydroxymethylfurfural (5-HMF) significantly inhibited ethanol fermentation, while levulinic acid (LA) was benign in the range up to 10 g/L.

Relation between preoperative autonomic function and blood pressure change after tourniquet deflation during total knee replacement arthroplasty.

BACKGROUND: Tourniquets are used to provide a bloodless surgical field for extremities. Hypotension due to vasodilation and bleeding after tourniquet deflation is a common event. Hemodynamic stability is modulated by the autonomic nervous system (ANS). Heart rate variability (HRV) is a sensitive method for detecting individuals who may be at risk of hemodynamic instability during general anesthesia. The purpose of this study was to investigate ANS function to predict hypotension after tourniquet deflation. METHODS: Eighty-six patients who underwent total knee replacement arthroplasty (TKRA) were studied. HRV, systolic blood pressure variability (SBPV) and baroreflex sensitivity (BRS) were analyzed. We assigned two groups depending on the lowest systolic blood pressure (SBP) or mean BP (MBP) after tourniquet release (Group H; SBP < 80 mmHg or MBP < 60 mmHg, Group S; SBP > 80 mmHg and MBP > 60 mmHg). RESULTS: Fifteen patients developed severe hypotension and ten patients were treated with ephedrine. Of the parameters of HRV, SBPV, and BRS, only BRS(SEQ) was significant being low in Group H. BRS and high-frequency SBPV were correlated with the degree of MBP change after tourniquet deflation. CONCLUSIONS: Preoperative low BRS is associated with hypotension after tourniquet deflation, suggesting the importance of baroreflex regulation for intraoperative hemodynamic stability.

Laboratory variables associated with low near-infrared cerebral oxygen saturation in icteric patients before liver transplantation surgery.

BACKGROUND: Although regional cerebral oxygen saturation (rSO2) measurements can detect disturbances in cerebral oxygenation, their usefulness is limited in patients with hyperbilirubinemia. We examined the relationship between rSO2 and other laboratory variables that may affect interpretation of low rSO2 in awake patients with end-stage liver disease before liver transplantation surgery. METHODS: Before induction of general anesthesia, rSO2 was measured in 164 patients with liver cirrhosis (Child class A/B/C = 19/41/104) and 8 with fulminant hepatic failure. Patients with West Haven hepatic encephalopathy of grade 3 or 4 were excluded. Relationships between rSO2 and laboratory variables were evaluated by correlation and multivariate regression, and by receiver operating characteristic curve analysis. RESULTS: Univariate analyses showed that rSO2 (median 58.5%, range 15% to 82%) correlated with serum total bilirubin, hemoglobin (Hb), creatinine, sodium, and magnesium concentrations, and prothrombin time (P < 0.001 each), but not with serum concentrations of glucose, albumin, potassium, and ammonia. Multiple logistic regression analysis showed that only elevated total bilirubin (range 0.4 to 66 mg/dL; odds ratio [OR] = 1.31; 95% confidence interval [CI] = 1.18 to 1.45) and low Hb (range 5.3 to 15.7 g/dL; OR = 0.21; 95% CI = 0.11 to 0.43) were independently related to rSO2 <50%. The optimum cutoff points for observing an rSO2 < 50% were total bilirubin >7.2 mg/dL (sensitivity 89%, specificity 90%) and Hb <9.6 g/dL (sensitivity 70%, specificity 82%). CONCLUSIONS: High total bilirubin and low Hb concentrations were independently associated with rSO2 values below 50% in end-stage liver disease patients awaiting liver transplantation. The results of this study identify patients in whom a low rSO2 may be an artifact rather than cerebral ischemia.

Experience without using venoveno bypass in adult orthotopic liver transplantation.

BACKGROUND: Venoveno bypass (VVB) has been used to achieve hemodynamic stability and decrease the incidence of renal dysfunction. However, VVB has many complications. The purpose of this study is to verify the safety of total clamping of the suprahepatic inferior vena cava (IVC) without VVB during orthotropic liver transplantation (OLT) in terms of anesthetic management. METHODS: Twenty-five patients without preoperative renal dysfunction who underwent primary OLT were enrolled in this study. Hemodynamic data and blood gas measurements were collected 1 hour after incision, 30 minutes after IVC total clamping and 30 minutes after reperfusion. Postoperative laboratory data, including blood urea nitrogen (BUN), creatinine (Cr) and glomerular filtration rate (GFR), were assessed at postoperative day (POD) 0-7, 30, 90, 180 and 1 year. RESULTS: Mean blood pressure was well maintained during IVC total clamping with infusion of inotropics. There was no case of severe acidosis (pH < 7.2) during the anhepatic period. The immediate postoperative Cr and GFR were not significantly different from those of the preoperative values. BUN increased from POD 1 and decreased after POD 6, while Cr increased at POD 90 only. CONCLUSIONS: In patients without preoperative renal dysfunction, when IVC was totally clamped, VVB does not need to be routinely performed to maintain hemodynamics during the anhepatic phase and renal function after OLT.

Pleural effusion caused by extravasation of irrigation fluid during arthroscopic shoulder surgery: A case report.

Arthroscopic shoulder surgery has become a common and routine procedure because it provides several advantages for the diagnosis and therapy of shoulder injuries. However, shoulder arthroscopy is not a technique that's void of complications. We describe here a unique case of a patient who experienced pleural effusion caused by extravasation of irrigation fluid during arthroscopic shoulder surgery, and this surgery was done under general anesthesia.

Altered autonomic cardiovascular regulation after combined deep and superficial cervical plexus blockade for carotid endarterectomy.

Compromised cardiac autonomic modulation can produce cardiovascular disturbances. We investigated whether combined deep and superficial cervical plexus (CP) blockade for carotid endarterectomy (CEA) produces changes in autonomic cardiovascular regulation. To estimate alterations in cardiovascular autonomic control before and after combined CP blockade in 22 patients undergoing CEA, the heart rate (HR) variability, systolic blood pressure (SBP) variability, and baroreflex sensitivity were analyzed. We found that SBP (157 +/- 28 mm Hg versus 191 +/- 38 mm Hg before and after combined CP blockade, respectively) and HR (68 +/- 10 bpm versus 84 +/- 9 bpm) increased after combined CP blockade. The high frequency power of HR variability (3.7 +/- 0.9 versus 2.2 +/- 1.2 ln/ms2) decreased (decrease in parasympathetic drive), whereas the low frequency power of SBP variability (5.5 +/- 4.7 versus 8.6 +/- 9.4 mm Hg2) increased (increase in vascular sympathetic outflow). Baroreflex sensitivity decreased, and this decrease was negatively correlated with a SBP increase (r = -0.455). The present results suggest that combined CP blockade impairs autonomic cardiovascular homeostasis and suggests an association between combined CP blockade and intraoperative or postoperative adverse cardiovascular events in high-risk cardiac patients undergoing CEA that merits further studies.

Low-dose atropine amplifies cardiac vagal modulation and increases dynamic baroreflex function in humans.

It has been previously known that low-dose atropine (LDA) enhances vagal outflow to the heart. To demonstrate the importance of vagal cardiac modulation in arterial blood pressure (ABP) stability, we evaluated the effect of vagal cardiac stimulation with administration of LDA on ABP fluctuation during dynamic hypertensive and hypotensive stimuli. We assessed changes in RR interval (RRI), ABP, power spectral densities of heart rate variability (HRV) and ABP variability, and spontaneous baroreflex sensitivity (BRS) in 16 healthy volunteers before and after administration of LDA (2 microg/kg). Transient hypertension was induced by phenylephrine (2 microg/kg), whereas hypotension was induced by bilateral thigh cuff deflation after a 3-min suprasystolic occlusion. LDA elicited bradycardia and significantly increased high-frequency (HF, 0.15-0.4 Hz) power of HRV and spontaneous BRS, as determined by transfer function analysis. The increase in systolic blood pressure (SBP) after phenylephrine administration was significantly attenuated by LDA (16+/-2 to 11+/-3 mmHg, P<0.005) and was associated with the augmented reflex bradycardia, whereas the decrease in SBP after cuff deflation was not affected (14+/-5 to 13+/-5 mmHg) with the augmented reflex tachycardia. Increases of HF HRV were correlated significantly and negatively with the increased SBP induced by phenylephrine before and after LDA (r=-0.502, P<0.05). These data suggest that the increased vagal cardiac function induced by LDA augments HR buffering effects, and is important in minimizing arterial pressure fluctuation during dynamic hypertensive stimuli.