Machine Learning Model for Anesthetic Risk Stratification for Gynecologic and Obstetric Patients: A Novel Approach for Early Detection.

BACKGROUND: Preoperative evaluation is important, our study explored the application of machine learning methods for anesthetic risk classification and for the evaluation of the contributions of various factors. To minimize the effects of confounding variables during model training, we used a homogenous group with similar physiological states and ages undergoing similar pelvic organ-related procedures not involving malignancies. OBJECTIVE: Data on women of reproductive age (age = 20-50 years) who underwent gestational or gynecological surgery between January 1, 2017, and December 31, 2021, were obtained from the National Taiwan University Hospital Integrated Medical Database. METHODS: We first performed an exploratory analysis and selected key features. We then performed data preprocessing to acquire relevant features related to preoperative examination. To further enhance predictive performance, we employed the log likelihood ratio algorithm to generate comorbidity patterns. Lastly, we input the processed features into the light gradient boosting machine (LightGBM) model for training and subsequent prediction. RESULTS: A total of 10,892 patients were included. Within this data set, 9893 patients were classified as having low anesthetic risk (American Society of Anesthesiologists physical status score 1-2), and 999 patients were classified as having high anesthetic risk (American Society of Anesthesiologists physical status score > 2). The area under the receiver operating characteristic curve of the LightGBM model was 90.25. CONCLUSIONS: By combining comorbidity information and clinical laboratory data, our methodology based on the LightGBM model provides more accurate predictions for anesthetic risk classification. CLINICALTRIAL: This study was registered with the Research Ethics Committee of the National Taiwan University Hospital with trial number 202204010RINB.

Next-generation sequencing and bioinformatics to identify genetic causes of malignant hyperthermia.

BACKGROUND/PURPOSE: Malignant hyperthermia (MH) is a life-threatening pharmacogenetic disease with only two known causative genes, RYR1 and CACNA1S. Both are huge genes containing numerous exons, and they reportedly only account for 50-70% of known MH patients. Next-generation sequencing (NGS) technology and bioinformatics could help delineate the genetic diagnosis of MH and several MH-like clinical presentations. METHODS: We established a capture-based targeted NGS sequencing framework to examine the whole genomic regions of RYR1, CACNA1S and the 16.6 Kb mitochondrial genome, as well as 12 other genes related to excitation-contraction coupling and/or skeletal muscle calcium homeostasis. We applied bioinformatics analyses to the variants identified in this study and also to the 48 documented RYR1 pathogenic variants. RESULTS: The causative variants were identified in seven of the eight (87.5%) MH families, but in none of the 10 individuals classified as either normal controls (N = 2) or patients displaying MH-like clinical features later found to be caused by other etiologies (N = 8). We showed that RYR1 c.1565A>G (p.Tyr522Cys)(rs118192162) could be a genetic hot spot in the Taiwanese population. Bioinformatics analyses demonstrated low population frequencies and predicted damaging effects from all known pathogenic RYR1 variants. We estimated that more than one in 1149 individuals worldwide carry MH pathogenic variants at RYR1. CONCLUSION: NGS and bioinformatics are sensitive and specific tools to examine RYR1 and CACNA1S for the genetic diagnosis of MH. Pathogenic variants in RYR1 can be found in the majority of MH patients in Taiwan.

Medical students' affective reactions to workplace experiences: qualitative investigation in a Chinese cultural context.

BACKGROUND: Compassion fatigue, unprofessional behavior, and burnout are prompting educators to examine medical students' affective reactions to workplace experiences. Attributes of both students and learning environments are influenced by their socio-cultural backgrounds. To prevent 'educational cultural hegemony', opinion leaders have advocated research in under-represented cultural contexts, of which Asia is a prime example. This study aimed to broaden the discourse of medical education by answering the question: how do students react affectively to workplace experiences in a Chinese cultural context? METHODS: In 2014, the authors recruited five female and seven male Taiwanese clerkship students to make 1-2 audio-diary recordings per week for 12 weeks describing affective experiences, to which they had consciously reacted. The authors analyzed transcripts of these recordings thematically in the original Mandarin and prepared a thick description of their findings, including illustrative extracts. An English-speaking education researcher helped them translate this into English, constantly comparing the interpretation with the original, untranslated data. RESULTS: (Mis) matches between their visions of future professional life and clerkship experiences influenced participants' affective reactions, thoughts, and behaviors. Participants managed these reactions by drawing on a range of personal and social resources, which influenced the valence, strength, and nature of their reactions. This complex set of interrelationships was influenced by culturally determined values and norms, of which this report provides a thick description. CONCLUSION: To avoid educational cultural hegemony, educators need to understand professional behavior in terms of complex interactions between culturally-specific attributes of individual students and learning environments. TRIAL REGISTRATION: The ethics committee of the National Taiwan University (NTU) Hospital gave research ethics approval ( 20130864RINB ).

Metabolomic Analysis of Platelets of Patients With Aspirin Non-Response.

Background: Aspirin is the most commonly used antiplatelet agent for the prevention of cardiovascular diseases. However, a certain proportion of patients do not respond to aspirin therapy. The mechanisms of aspirin non-response remain unknown. The unique metabolomes in platelets of patients with coronary artery disease (CAD) with aspirin non-response may be one of the causes of aspirin resistance. Materials and Methods: We enrolled 29 patients with CAD who were aspirin non-responders, defined as a study subject who were taking aspirin with a platelet aggregation time less than 193 s by PFA-100, and 31 age- and sex-matched patients with CAD who were responders. All subjects had been taking 100 mg of aspirin per day for more than 1 month. Hydrophilic metabolites from the platelet samples were extracted and analyzed by nuclear magnetic resonance (NMR). Both 1D 1H and 2D J-resolved NMR spectra were obtained followed by spectral processing and multivariate statistical analysis, such as partial least squares discriminant analysis (PLS-DA). Results: Eleven metabolites were identified. The PLS-DA model could not distinguish aspirin non-responders from responders. Those with low serum glycine level had significantly shorter platelet aggregation time (mean, 175.0 s) compared with those with high serum glycine level (259.5 s). However, this association became non-significant after correction for multiple tests. Conclusions: The hydrophilic metabolic profile of platelets was not different between aspirin non-responders and responders. An association between lower glycine levels and higher platelet activity in patients younger than 65 years suggests an important role of glycine in the pathophysiology of aspirin non-response.

The critical role of respiratory sinus arrhythmia on temporal cardiac dynamics.

Temporal cardiac properties provide alternative information in analyzing heart rate variability (HRV), which may be disregarded by the standard HRV analyses. Patients with congestive heart failure (CHF) are known to have distinct temporal features from the healthy individuals. However, the underlying mechanism leading to the variation remains unclear. Whether or not these parameters can finely classify the severity for CHF patients is uncertain as well. In this work, an electrocardiogram was monitored in advanced CHF patients using 24-h Holter in four conditions, including baseline, one and three months after atenolol therapy, and healthy individuals. Slope and area under the curve (AUC) of multiscale entropy (MSE) curve over short (scales 1-5) and long (scales 6-20) scales, and detrended fluctuation analysis (DFA) scaling exponents at short (4-11 beats) and intermediate (>11 beats) window sizes were calculated. The results show that short-time scale MSE-derived parameters (slope: -0.08 ± 0.10, -0.03 ± 0.10, 0.02 ± 0.06, 0.08 ± 0.06; AUC: 4.03 ± 2.11, 4.69 ± 1.28, 4.73 ± 0.94, and 6.17 ± 1.23) and short-time scale DFA exponent (0.79 ± 0.16, 0.95 ± 0.22, 1.11 ± 0.19, and 1.35 ± 0.20) can hierarchically classify all four conditions. More importantly, simulated R-R intervals with different fractions and amplitude of respiratory sinus arrhythmia (RSA) components were examined to validate our hypothesis regarding the essentiality of RSA in the improvement of cardiovascular function, and its tight association with unpredictability and fractal property of HRV, which is in line with our hypothesis that RSA contributes significantly to the generation of the unpredictability and fractal behavior of HR dynamics.NEW & NOTEWORTHY Temporal cardiac properties provide useful diagnostic parameters for patients with congestive heart failure (CHF). Our study hierarchically classified CHF patients with ß-blocker treatment by using multiscale entropy and detrended fluctuation analysis. Also, we provided the evidence to validate the critical role of respiratory sinus arrhythmia in the fractal properties of heart rate variability.

Associations between Peripheral Thromboembolic Vascular Disease and Androgen Deprivation Therapy in Asian Prostate Cancer Patients.

This study aimed to investigate the risks of thromboembolic vascular disease following androgen deprivation therapy (ADT) administered to prostate cancer (PCa) patients. A total of 24,464 men with newly diagnosed PCa during 2000-2008 were recruited through a longitudinal health insurance database in Taiwan. All PCa patients were stratified into two: ADT and non-ADT groups. Patients with ADT treatment were grouped into three: surgical castration, chemical castration, and anti-androgen alone. The risks of pulmonary embolism (PE), peripheral arterial occlusion disease (PAOD), and deep vein thrombosis (DVT) were assessed in multiple Cox proportional-hazards regression with time-dependent covariates. During the 12-year follow-up period, incidence rates per 1000 person-years in ADT and non-ADT groups were 2.87 and 1.62 for DVT, 1.00 and 0.52 for PE, and 1.03 and 0.70 for PAOD, respectively. The DVT and PE risks were significantly increased in patients receiving combined androgen blockade (CAB) compared with the counterpart ADT non-recipients. After adjusting for potential risk factors, PCa patients receiving CAB had the highest PE risk (HR = 3.11), followed by DVT risk (HR = 2.53). The DVT risk remained elevated throughout the entire duration of chemical castration. However, high PE risk was observed in patients with ≤720-day treatment duration. No association was found between ADT and PAOD risks. Overall, the risks of PE and DVT were considerably heightened in Asian men subjected to CAB for PCa, whereas PAOD risk was unrelated to such treatments.

An observational study: The utility of perfusion index as a discharge criterion for pain assessment in the postanesthesia care unit.

Acute post-operative pain can remain untreated if patients cannot express themselves. The perfusion index (PI) may decrease when pain activates sympathetic tone and may increase after analgesics are administered. We evaluated if the perfusion index is a feasible indicator for objectively assessing pain relief in the postanesthesia care unit (PACU) and calculated the changes in PI measurements at the time of discharge from the PACU relative to baseline PI measurements to examine if the PI is a useful criterion for discharging patients from the postanesthesia care unit. This retrospective observational study enrolled female patients who were admitted for gynecological or general surgery. The patients received general anesthesia and were admitted to the postanesthesia care unit. The PI, visual analogue scale (VAS) score, heart rate, and blood pressure were recorded before and after administration of intravenous morphine. Changes in these parameters before and after analgesics were administered and the difference of these parameters between age and BMI subgroups were compared. The correlation between the PI and VAS score, ΔPI and ΔVAS, and %ΔPI and %ΔVAS were also evaluated. The percentage change in ΔPI (P9-T0/T0) of the patients at the time of discharge from the postanesthesia care unit relative to baseline PI measurements was calculated. Eighty patients were enrolled, and there were 123 instances during which analgesia was required. Heart rate, PI, and VAS score were significantly different before and after analgesics were administered (p < 0.0001). The difference of parameters between age and BMI subgroups were not significant. The correlation between the PI and VAS score, ΔPI and ΔVAS, and the percentage change in ΔPI and ΔVAS showed weak correlations in age, BMI subgroups, and all measurements. The baseline PI and the PI when arriving at and when being discharged from the postanesthesia care unit were significantly different (p < 0.01). The mean percentage change in Δ PI at the time of discharge from the PACU was 66.2%, and the 99% confidence interval was 12.2%~120.3%. The perfusion index was increased, and the VAS score was decreased significantly after analgesics were administered, but the correlation was weak in each subgroup. The VAS score is a subjective and psychometric parameter. The PI increased when partial pain relief was achieved after morphine was administered but did not reflect pain intensity or changes in the VAS score regardless of age or BMI. A percentage change in ΔPI at the time of discharge from the PACU relative to baseline PI measurements of greater than 12% can be used as a supplemental objective discharge criterion for pain assessment in the postanesthesia care unit.

Biomarkers and echocardiography for evaluating the improvement of the ventricular diastolic function after surgical relief of hydronephrosis.

The pathophysiology of cardio-renal syndrome (CRS) is complex. Hydronephrosis caused by urolithiasis may cause cytokine release and lead to cardiac dysfunction. The aim of this study was to evaluate cardiac function changes observed in patients who received double J placement using feasible biomarkers and echocardiography. This was a prospective, single-center study. Eighty-seven patients who presented with acute unilateral hydronephrosis and received ureteroscope stone manipulation were enrolled. Echocardiography and cytokines were measured on the day of the operation and 24 hours after the procedure. Changes before and after surgery were assessed by the paired t-test and Wilcoxon test. Correlation analyses between echocardiographic diastolic indices and cytokine levels were performed using Pearson's correlation coefficients. Patients with hydronephrosis showed a higher left atrium volume index (LAVI), decreased E', and increased E/ E' ratio, which indicated diastolic dysfunction. Patients with hydronephrosis also exhibited decreased global strain rates during isovolumetric relaxation (SRIVR) and E/ SRIVR, which confirmed the diastolic dysfunction. Significant reductions in LAVI, increases in SRIVR and decreases in E/ SRIVR were observed after the operation. Biomarkers, such as TGF-ß and serum NT-proBNP, were significantly decreased after surgery. In addition, a significant correlation was observed between the post-surgical decrease in TGF-ß1 and increase in SRIVR. Unilateral hydronephrosis causes cardiac diastolic dysfunction, and relieving hydronephrosis could improve diastolic function. Improvements in cardiac dysfunction can be evaluated by echocardiography and measuring cytokine levels. The results of this study will inform efforts to improve the early diagnosis of CRS and prevent further deterioration of cardiac function when treating patients with hydronephrosis.

Leading Comorbidity associated with 30-day post-anesthetic mortality in geriatric surgical patients in Taiwan: a retrospective study from the health insurance data.

BACKGROUND: Elderly patients with aged physical status and increased underlying disease suffered from more postoperative complication and mortality. We design this retrospective cohort study to investigate the relationship between existing comorbidity of elder patients and 30 day post-anesthetic mortality by using International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) from Health Insurance Database. METHODS: Patients aged above 65 years old who received anesthesia between 2000 and 2010 were included from 1 million Longitudinal Health Insurance Database in (LHID) 2005 in Taiwan. We use age, sex, type of surgery to calculate propensity score and match death group and survival one with 1:4 ratio (death: survival = 1401: 5823). Multivariate logistic model with stepwise variable selection was employed to investigate the factors affecting death 30 days after anesthesia. RESULTS: Thirty seven comorbidities can independently predict the post-anesthetic mortality. In our study, the leading comorbidities predict post-anesthetic mortality is chronic renal disease (OR = 2.806), acute myocardial infarction (OR = 4.58), and intracranial hemorrhage (OR = 3.758). CONCLUSIONS: In this study, we present the leading comorbidity contributing to the postoperative mortality in elderly patients in Taiwan from National Health Insurance Database. Chronic renal failure is the leading contributing comorbidity of 30 days mortality after anesthesia in Taiwan which can be explained by the great number of hemodialysis and prolong life span under National Taiwan Health Insurance. Large scale database can offer enormous information which can help to improve quality of medical care.

Emotional Learning and Identity Development in Medicine: A Cross-Cultural Qualitative Study Comparing Taiwanese and Dutch Medical Undergraduates.

PURPOSE: Current knowledge about the interplay between emotions and professional identity formation is limited and largely based on research in Western settings. This study aimed to broaden understandings of professional identity formation cross-culturally. METHOD: In fall 2014, the authors purposively sampled 22 clinical students from Taiwan and the Netherlands and asked them to keep audio diaries, narrating emotional experiences during clerkships using three prompts: What happened? What did you feel/think/do? How does this interplay with your development as a doctor? Dutch audio diaries were supplemented with follow-up interviews. The authors analyzed participants' narratives using a critical discourse analysis informed by Figured Worlds theory and Bakhtin's concept of dialogism, according to which people's spoken words create identities in imagined future worlds. RESULTS: Participants talked vividly, but differently, about their experiences. Dutch participants' emotions related to individual achievement and competence. Taiwanese participants' rich, emotional language reflected on becoming both a good person and a good doctor. These discourses constructed doctors' and patients' autonomy in culturally specific ways. The Dutch construct centered on "hands-on" participation, which developed the identity of a technically skilled doctor, but did not address patients' self-determination. The Taiwanese construct located physicians' autonomy within moral values more than practical proficiency, and gave patients agency to influence doctor-patient relationships. CONCLUSIONS: Participants' cultural constructs of physician and patient autonomy led them to construct different professional identities within different imagined worlds. The contrasting discourses show how medical students learn about different meanings of becoming doctors in culturally specific contexts.

Becoming a Doctor in Different Cultures: Toward a Cross-Cultural Approach to Supporting Professional Identity Formation in Medicine.

Becoming a doctor is fundamentally about developing a new, professional identity as a physician, which in and of itself may evoke many emotions. Additionally, medical trainees are increasingly moving from one cultural context to another and are challenged with navigating the resulting shifts in their professional identify. In this Article, the authors aim to address medical professional identity formation from a polyvocal, multidisciplinary, cross-cultural perspective. They delineate the cultural approaches to medical professionalism, reflect on professional identity formation in different cultures and on different theories of identity development, and advocate for a context-specific approach to professional identity formation. In doing so, the authors aim to broaden the developing professional identity formation discourse to include non-Western approaches and notions.

Unique clinical characteristics and SCN5A mutations in patients with Brugada syndrome in Taiwan.

BACKGROUND/PURPOSE: Brugada syndrome (BrS) is a hereditable sudden cardiac death (SCD). Mutations in the SCN5A gene (the most common BrS-causing gene) are responsible for 20-25% of this disease in Caucasian populations. However, the prevalence of SCN5A mutations in patients with BrS in the Chinese Han population in Taiwan remains unknown. Therefore, in this study, we investigated the prevalence of the SCN5A mutation in the largest BrS cohort in Taiwan. METHODS: We consecutively enrolled 47 unrelated patients with BrS from medical centers and hospitals in Taiwan between 2000 and 2010. Mutations within all the 27 translated exons, and exon-intron boundaries of the SCN5A-encoded cardiac sodium channel were screened in all patients with BrS using direct sequencing. A total of 500 unrelated healthy volunteers with a normal electrocardiogram were genotyped as a control group. RESULTS: SCN5A genetic variants were identified in 14 of the 47 patients with BrS and four of the 14 patients with BrS had missense mutations (1651 G>A, 1776 C>G, 3578 G>A). The prevalence rate of SCN5A mutations was approximately 8% (4/47), which was significantly lower than that reported in Caucasian populations (20-25%; p = 0.0007). The average age of these 14 BrS patients with SCN5A variants at diagnosis (12 men and 2 women) was 40 ± 13 years. Four patients experienced SCD, and six presented with seizure or syncope. Only three patients (3/14, 21.4%) had a family history of SCD. CONCLUSION: The prevalence of SCN5A mutations in the Chinese Han population in Taiwan may be lower than that reported in the Caucasian populations. In addition, most patients with BrS did not have a family history of SCD.

A new method to derive fetal heart rate from maternal abdominal electrocardiogram: monitoring fetal heart rate during cesarean section.

BACKGROUND: Monitoring of fetal heart rate (FHR) is important during labor since it is a sensitive marker to obtain significant information about fetal condition. To take immediate response during cesarean section (CS), we noninvasively derive FHR from maternal abdominal ECG. METHODS: We recruited 17 pregnant women delivered by elective cesarean section, with abdominal ECG obtained before and during the entire CS. First, a QRS-template is created by averaging all the maternal ECG heart beats. Then, Hilbert transform was applied to QRS-template to generate the other basis which is orthogonal to the QRS-template. Second, maternal QRS, P and T waves were adaptively subtracted from the composited ECG. Third, Gabor transformation was applied to obtain time-frequency spectrogram of FHR. Heart rate variability (HRV) parameters including standard deviation of normal-to-normal intervals (SDNN), 0V, 1V, 2V derived from symbolic dynamics of HRV and SD1, SD2 derived from Poincareé plot. Three emphasized stages includes: (1) before anesthesia, (2) 5 minutes after anesthesia and (3) 5 minutes before CS delivery. RESULTS: FHRs were successfully derived from all maternal abdominal ECGs. FHR increased 5 minutes after anesthesia and 5 minutes before delivery. As for HRV parameters, SDNN increased both 5 minutes after anesthesia and 5 minutes before delivery (21.30±9.05 vs. 13.01±6.89, P < 0.001 and 22.88±12.01 vs. 13.01±6.89, P < 0.05). SD1 did not change during anesthesia, while SD2 increased significantly 5 minutes after anesthesia (27.92±12.28 vs. 16.18±10.01, P < 0.001) and both SD2 and 0V percentage increased significantly 5 minutes before delivery (30.54±15.88 vs. 16.18±10.01, P < 0.05; 0.39±0.14 vs. 0.30±0.13, P < 0.05). CONCLUSIONS: We developed a novel method to automatically derive FHR from maternal abdominal ECGs and proved that it is feasible during CS.

Perfusion index derived from a pulse oximeter can detect changes in peripheral microcirculation during uretero-renal-scopy stone manipulation (URS-SM).

BACKGROUND: The objective of this study was to test the effect of removal of a ureteral obstruction (renal calculus) from anesthetized patients on the perfusion index (PI), as measured by a pulse oximeter, and on the estimated glomerular filtration rate (eGFR). PATIENTS AND METHODS: This prospective study enrolled 113 patients with unilateral ureteral obstructions (kidney stones) who were scheduled for ureteroscopy (URS) laser lithotripsy. One urologist graded patient hydronephrosis before surgery. A pulse oximeter was affixed to each patient's index finger ipsilateral to the intravenous catheter, and a non-invasive blood pressure cuff was placed on the contralateral side. Ipsilateral double J stents and Foley catheters were inserted and left indwelling for 24 h. PI and mean arterial pressure (MAP) were determined at baseline, 5 min after anesthesia, and 10 min after surgery; eGFR was determined at admission, 1 day after surgery, and 14 days after surgery. RESULTS: Patients with different grades of hydronephrosis had similar age, eGFR, PI, mean arterial pressure (MAP), and heart rate (HR). PI increased significantly in each hydronephrosis group after ureteral stone disintegration. None of the groups had significant post-URS changes in eGFR, although eGFR increased in the grade I hydronephrosis group after 14 days. The percent change of PI correlates significantly with the percent change of MAP, but not with that of eGFR. CONCLUSION: Our results demonstrate that release of a ureteral obstruction leads to a concurrent increase of PI during anesthesia. Measurement of PI may be a valuable tool to monitor the successful release of ureteral obstructions and changes of microcirculation during surgery. There were also increases in eGFR after 14 days, but not immediately after surgery.

Clinical characteristics of patients with congenital long QT syndrome and bigenic mutations.

BACKGROUND: Congenital long QT syndrome (LQTS) is an ion channelopathy associated with genetic mutations. It is well known that most LQTS patients (91%) have a single mutation. The purpose of this study was to investigate the clinical characteristics of congenital LQTS patients with bigenic mutations in Taiwan, China. METHODS: Congenital LQTS patients were recruited consecutively at Taiwan University Hospital in Taiwan from 2003 to 2009. The diagnosis of LQTS was defined by an LQTS Schwartz score greater than 4. Mutation screening in KCNQ1, KCNH2, KCNE1, and SCN5A was performed using direct sequencing. RESULTS: Three of 16 LQTS patients (18.7%) were identified with bigenic mutations. One patient had missense mutations in KCNQ1 and KCNH2, the second in KCNQ1 and KCNE1, and the third in KCNH2 and SCN5A. The mean age at onset of LQTS for patients with bigenic mutations was (17 ± 3) years, and all of these patients were female. Two of them experienced seizure and one presented with syncope, although one of them had a family history of syncope. The mean QTc interval was (515 ± 17) ms, similar to those with single mutation or SNPs ((536 ± 74) ms, P = 0.63). Compared to those LQTS patients with single mutation or SNPs, a significantly higher percentage of LQTS patients with bigenic mutations presented with seizure and were younger at onset of the first index event (P = 0.03 and 0.001, respectively), but lower percentage of them presented with sudden cardiac death (P = 0.03). CONCLUSIONS: Although the percentage of bigenic mutations in LQTS is less than 10% in Caucasian populations, we identified 3 of 16 LQTS patients (18.7%, 95% confidence interval: 0.04-0.46) with bigenic mutations in Taiwan. However, the severity of their clinical presentations was not higher than those patients with single mutation or SNPs.

Connective tissue growth factor and cardiac diastolic dysfunction: human data from the Taiwan diastolic heart failure registry and molecular basis by cellular and animal models.

AIMS: Connective tissue growth factor (CTGF) is an emerging marker for tissue fibrosis. We investigated the association between CTGF and cardiac diastolic function using cellular and animal models and clinical human data. METHODS AND RESULTS: A total of 125 patients with a diagnosis of diastolic heart failure (DHF) were recruited from 1283 patients of the Taiwan Diastolic Heart Failure Registry. The severity of DHF was determined by tissue Doppler imaging (E/e'). Cardiac magnetic resonance imaging (CMRI) was used to evaluate myocardial fibrosis in some of the patients (n = 25). Stretch of cardiomyocytes on a flexible membrane base serves as a cellular phenotype of cardiac diastolic dysfunction (DD). A canine model of DD was induced by aortic banding. A significant correlation was found between plasma CTGF and E/e' in DHF patients. The severity of cardiac fibrosis evaluated by CMRI also correlated with CTGF. In the cell model, stretch increased secretion of CTGF from cardiomyocytes. In the canine model, myocardial tissue CTGF expression and fibrosis significantly increased after 2 weeks of aortic banding. Notably, the expression of CTGF paralleled the severity of LV DD (r = 0.40, P < 0.001 for E/e') and haemodynamic changes (r = 0.80, P < 0.001). After adjusting for confounding factors, CTGF levels still correlated with diastolic parameters in both human and canine models (human plasma CTGF, P < 0.001; canine tissue CTGF, P = 0.04). CONCLUSION: Plasma CTGF level correlated with the severity of DD and tissue fibrosis in DHF patients. The mechanism may be through myocardial stretch. Our study indicated that CTGF may serve as an early marker for DHF.

Additive effect of the metabolic syndrome score to the conventional CHADS2 score for the thromboembolic risk stratification of patients with atrial fibrillation.

BACKGROUND: The CHA2DS2-VASC scoring scheme may not be better than the CHADS2 scoring scheme in predicting thromboembolic risk for patients with atrial fibrillation (AF) in Asians. Metabolic syndrome is associated with an increased risk of thrombosis. OBJECTIVE: To evaluate whether metabolic syndrome offers incremental information over the CHADS2 scheme in predicting thromboembolic risk for patients with AF in the Taiwanese population. METHODS: The study population consisted of 721 consecutive patients with AF who had been followed up for a median of 10.8 years. Thromboembolic end points were defined as ischemic stroke/transient ischemic accident and peripheral embolisms. Clinical factors associated with thromboembolic end points were identified by Cox regression analysis. Different scoring systems were compared by receiver operating characteristic (ROC) analysis. RESULTS: We found that components in the CHADS2 scheme were associated with an increased risk of thromboembolism. The CHA2DS2-VASC scheme did not provide information additional to that provided by the CHADS2 scheme on thromboembolism risk (ROC area: 0.670 vs 0.665; P > .05). Metabolic syndrome components were also associated with increased risk of thromboembolism. The incident thromboembolic rate increased incrementally when metabolic syndrome score increased. Additional metabolic syndrome components provide additional information to the CHADS2 scheme on thromboembolism risk (ROC area: 0.670 vs 0.729; P = .034). We therefore proposed a new scoring scheme called CHADS2-MS scoring scheme. In patients with low to intermediate CHADS2 scores (0-1), the use of the CHADS2-MS score may additionally identify patients with high-risk AF for future thromboembolism. CONCLUSIONS: We, for the first time, demonstrated that metabolic syndrome components were associated with thromboembolic risk in Taiwanese patients with AF. In addition to the conventional CHADS2 scheme, the calculation of the CHADS2-MS score provides additional information on stroke risk assessment.

Sex differences in conscious sedation during upper gastrointestinal panendoscopic examination.

BACKGROUND/PURPOSE: Sex differences in response to noxious stimuli or analgesia have been demonstrated. We investigated sex differences in conscious sedation during upper gastrointestinal panendoscopic examination with regard to drug dose and entropy scores. METHODS: We investigated sex differences in 30 men and 30 women who were undergoing conscious sedation during upper gastrointestinal panendoscopic examination. The drug mixture was prepared as 5 mg midazolam plus 1 mg alfentanil diluted with normal saline to a volume of 10 mL. An initial injection of 4 mL was followed by an additional 1 mL every 1 minute, until the modified Observer Assessment of Alertness and Sedation (OAAS) rating scale was ≤ 3 when the panendoscope was inserted. Further injection was allowed thereafter. Entropy values, including state entropy (SE) and response entropy (RE), were monitored from baseline to full recovery. RESULTS: The volume of mixture needed to achieve an OAAS score of ≤ 3 was significantly lower in men than in women (4.4 ± 0.7 mL vs. 4.8 ± 0.8 mL, p = 0.034). The initial drug demand was not significantly influenced by age, body weight, or body height. The RE and SE values at the time of panendoscope insertion were not significantly different between men and women. The total volume for men was also significantly lower than that for women (5.7 ± 1.1 mL vs. 6.5 ± 1.4 mL, p < 0.01). The lowest RE and SE values during the procedure were not significantly different between men and women. CONCLUSION: Women need more analgesic agents than men during panendoscopic examination. There was no significant difference between men and women with regard to anesthetic depth and response to noxious stimuli, as revealed by similar SE and RE values.

Is a pre-operative brain natriuretic peptide or N-terminal pro-B-type natriuretic peptide measurement an independent predictor of adverse cardiovascular outcomes within 30 days of noncardiac surgery? A systematic review and meta-analysis of observational studies.

OBJECTIVES: We conducted a systematic review and meta-analysis to determine if pre-operative brain natriuretic peptide (BNP) (i.e., BNP or N-terminal pro-B-type natriuretic peptide [NT-proBNP]) is an independent predictor of 30-day adverse cardiovascular outcomes after noncardiac surgery. BACKGROUND: Pre-operative clinical cardiac risk indices have only modest predictive power. BNP predicts adverse cardiovascular outcomes in a variety of nonsurgical settings and may similarly predict these outcomes in the perioperative setting. METHODS: We employed 5 search strategies (e.g., searching bibliographic databases), and we included all studies that assessed the independent prognostic value of pre-operative BNP measurement as a predictor of cardiovascular complications after noncardiac surgery. We determined study eligibility and conducted data abstraction independently and in duplicate. We calculated a pooled odds ratio using a random effects model. RESULTS: Nine studies met eligibility criteria, and included a total of 3,281 patients, among whom 314 experienced 1 or more perioperative cardiovascular complications. The average proportion of patients with elevated BNP was 24.8% (95% confidence interval [CI]: 20.1 to 30.4%; I(2) = 89%). All studies showed a statistically significant association between an elevated pre-operative BNP level and various cardiovascular outcomes (e.g., a composite of cardiac death and nonfatal myocardial infarction; atrial fibrillation). Data pooled from 7 studies demonstrated an odds ratio (OR) of 19.3 (95% CI: 8.5 to 43.7; I(2) = 58%). The pre-operative BNP measurement was an independent predictor of perioperative cardiovascular events among studies that only considered the outcomes of death, cardiovascular death, or myocardial infarction (OR: 44.2, 95% CI: 7.6 to 257.0, I(2) = 51.6%), and those that included other outcomes (OR: 14.7, 95% CI: 5.7 to 38.2, I(2) = 62.2%); the p value for interaction was 0.28. CONCLUSIONS: These results suggest that an elevated pre-operative BNP or NT-proBNP measurement is a powerful, independent predictor of cardiovascular events in the first 30 days after noncardiac surgery.