Jui-Ying Fu

Prediction of fluid responsiveness in acute respiratory distress syndrome patients ventilated with low tidal volume and high positive end-expiratory pressure*

Objective:Dynamic preload indicators with pulse pressure variation and stroke volume variation are superior to static indicators for predicting fluid responsiveness in mechanically ventilated patients. However, they are influenced by tidal volume and the level of positive end-expiratory pressure. The present study was designed to evaluate the clinical applicability of pulse pressure variation and stroke volume variation in predicting fluid responsiveness on acute respiratory distress syndrome patients ventilated with protective strategy (low tidal volume and high positive end-expiratory pressure). Design:Prospective, observational study. Setting:A 20-bed medical intensive care unit of a tertiary medical center. Patients:Twenty-two sedated and paralyzed early acute respiratory distress syndrome patients. Interventions:After being enrolled, central venous pressure, pulmonary capillary wedge pressure, and cardiac output index were obtained from a pulmonary artery catheter (OptiQ SvO2/CCO catheter), and intrathoracic blood volume, global end-diastolic volume, stroke volume variation, and pulse pressure variation were recorded from a PiCCOplus monitor. The whole set of hemodynamic measurements was performed before and after volume expansion with 500 mL hydroxyethyl starch (10% pentastarch 200/0.5). Measurements and Main Results:Cardiac output index, central venous pressure, pulmonary capillary wedge pressure, global end-diastolic volume, and intrathoracic blood volume significantly increased, and pulse pressure variation and stroke volume variation significantly decreased after volume expansion. Baseline pulse pressure variation significantly correlated with volume expansion-induced absolute changes (r = .62), or percent changes in cardiac output index (r = .75) after volume expansion. The area under the receiver operating characteristic curve was the highest for pulse pressure variation (area under the receiver operating characteristic curve = 0.768) than other indicators. The threshold value for baseline pulse pressure variation greater than 11.8% predicted a significant positive response to volume expansion with a sensitivity of 68% and a specificity of 100%. Conclusions:Baseline pulse pressure variation accurately predicted the fluid responsiveness in early acute respiratory distress syndrome patients. Roughly, a baseline pulse pressure variation greater than the threshold value of 12% is associated with a significant increase in cardiac output index after the end of volume expansion.

Induced pluripotent stem cell therapy ameliorates hyperoxia-augmented ventilator-induced lung injury through suppressing the Src pathway.

Background High tidal volume (VT) mechanical ventilation (MV) can induce the recruitment of neutrophils, release of inflammatory cytokines and free radicals, and disruption of alveolar epithelial and endothelial barriers. It is proposed to be the triggering factor that initiates ventilator-induced lung injury (VILI) and concomitant hyperoxia further aggravates the progression of VILI. The Src protein tyrosine kinase (PTK) family is one of the most critical families to intracellular signal transduction related to acute inflammatory responses. The anti-inflammatory abilities of induced pluripotent stem cells (iPSCs) have been shown to improve acute lung injuries (ALIs); however, the mechanisms regulating the interactions between MV, hyperoxia, and iPSCs have not been fully elucidated. In this study, we hypothesize that Src PTK plays a critical role in the regulation of oxidants and inflammation-induced VILI during hyperoxia. iPSC therapy can ameliorate acute hyperoxic VILI by suppressing the Src pathway. Methods Male C57BL/6 mice, either wild-type or Src-deficient, aged between 2 and 3 months were exposed to high VT (30 mL/kg) ventilation with or without hyperoxia for 1 to 4 h after the administration of Oct4/Sox2/Parp1 iPSCs at a dose of 5×107 cells/kg of mouse. Nonventilated mice were used for the control groups. Results High VT ventilation during hyperoxia further aggravated VILI, as demonstrated by the increases in microvascular permeability, neutrophil infiltration, macrophage inflammatory protein-2 (MIP-2) and plasminogen activator inhibitor-1 (PAI-1) production, Src activation, nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity, and malaldehyde (MDA) level. Administering iPSCs attenuated ALI induced by MV during hyperoxia, which benefited from the suppression of Src activation, oxidative stress, acute inflammation, and apoptosis, as indicated by the Src-deficient mice. Conclusion The data suggest that iPSC-based therapy is capable of partially suppressing acute inflammatory and oxidant responses that occur during hyperoxia-augmented VILI through the inhibition of Src-dependent signaling pathway.

Risk Factors and Possible Mechanisms of Intravenous Port Catheter Migration

OBJECTIVE To identify the risk factors for catheter migration and demonstrate possible mechanisms of this migration. DESIGN Retrospective study. SETTING Chang Gung Memorial Hospital, a tertiary medical centre in Taiwan. PATIENTS Patients who underwent implantation of intravenous ports via the superior vena cava (SVC). INTERVENTIONS Procedures involving catheter placement and re-intervention for catheter migration. MAIN OUTCOME MEASURES The anatomic location of the catheter tip was confirmed by plain chest X-rays (postero-anterior view). From these plain radiographs, the distance (in cm) between the carina and catheter tip and the angle (in degrees) between the locking nut and catheter were measured. METHODS A total of 1542 procedures related to intravenous port implantation were retrospectively reviewed but only procedures involving implantation via the SVC were included in the analysis. The study group was composed of 31 interventions because of catheter migration, while the control group consisted of 1475 implantation and re-intervention procedures except those involving catheter migrations. RESULTS Shallow catheter-tip location (p < 0.0001) and the presence of lung cancer (p = 0.006) were risk factors for catheter migration. CONCLUSIONS Shallow catheter-tip location and the presence of lung cancer are risk factors for catheter migration. Strategies that ensure low catheter-tip location and avoid increased thoracic pressure may be useful preventive measures.

Recurrence Risk Factors Analysis for Stage I Non-small Cell Lung Cancer.

AbstractLung cancer is the leading cause of cancer-related death worldwide. Even early-stage patients might encounter disease recurrence with relative high risk. Effective postoperative therapy is based on an accurate assessment of treatment failure after surgery. The aim of this study is to construct a disease-free survival (DFS) prediction model and stratify patients into different risk score groups.A total of 356 pathological stage I patients (7th American Joint Committee on Cancer) who underwent lung resection from January 2005 through June 2011 were retrospectively reviewed. Of these patients, 63 patients were eliminated for this study. A total of 293 p-stage I patients were included for further univariate and multivariate analysis. Clinical, surgical, and pathological factors associated with high risk of recurrence were analyzed, including age, gender, smoking status, additional primary malignancy (APM), operation method, histology, visceral pleural invasion, angiolymphatic invasion, tumor necrosis, and tumor size.Of the 293 p-stage I non-small cell lung cancer (NSCLC) patients examined, 143 were female and 150 were male, with a mean age of 62.8-years old (range: 25–83-years old). The 5-year DFS and overall survival rates after surgery were 58.9% and 75.3%, respectively. On multivariate analysis, current smoker (hazards ratio [HR]: 1.63), APM (HR: 1.86), tumor size (HR: 1.54, 2.03), nonanatomic resections (HR: 1.81), adenocarcinoma histology (HR: 2.07), visceral pleural invasion (HR: 1.54), and angiolymphatic invasion (HR: 1.53) were found to be associated with a higher risk of tumor recurrence. The final model showed a fair discrimination ability (C-statistic = 0.68). According to the difference risk group, we found patients with intermediate or higher risk group had a higher distal relapse tendency as compared with low risk group (P = 0.016, odds ratio: 3.31, 95% confidence interval: 1.21–9.03).Greater than 30% of disease recurrences occurred after surgery for stage I NSCLC patients. That is why we try to establish an effective DFS predicting model based on clinical, pathological, and surgical covariates. However, our initial results still need to be validated and refined into greater population for better application in clinical use.

Renal replacement therapy in prolonged mechanical ventilation patients with renal failure in Taiwan

BACKGROUND Renal failure requiring renal replacement therapy (RRT) is associated with a high mortality rate in intensive care unit (ICU) patients. Little information is available on the outcomes of patients having prolonged mechanical ventilation (PMV) in addition to RRT. The purpose of this study was to investigate the impact of RRT in PMV patients. METHODS This was an observational, retrospective study in the 24-bed respiratory care center (RCC) of Chang Gung Memorial Hospital, Taiwan, between May 2001 and April 2007. The end points were weaning rate and survival rate at the RCC. RESULTS Of the 1301 RCC patients, 157 patients (13.7%) underwent RRT. The RRT patients had lower successful weaning rate (39.5% vs 58.4%, P < .001) and RCC survival rate (45.9% vs 71.9%, P < .001) compared with without-RRT patients. The successful weaning rates of end-stage renal disease (ESRD) patients, patients with RRT initiated at the ICU and continued at RCC, and patients whose RRT was initiated at the RCC were 49.2%, 39.1%, and 22.2%, respectively. The RCC survival rates were 50.8%, 47.8%, and 29.6%, respectively. The odds ratios of successful weaning rate and survival rate were 0.295 (95% confidence interval, 0.105-0.833; P = .021) and 0.407 (95% confidence interval, 0.155-1.021; P = .069) for patients whose RRT was initiated at the RCC vs ESRD patients. CONCLUSION The present study demonstrates that the need for RRT had a negative impact on weaning and mortality in PMV patients compared with patients without RRT. Patients who had RRT initiated at the RCC had a significantly lower weaning rate compared with ESRD patients.

Prognostic value of metastatic N1 lymph node ratio and angiolymphatic invasion in patients with pathologic stage IIA non-small cell lung cancer.

AbstractWith regard to pathologic stage IIA (pIIA) non-small cell lung cancer (NSCLC), there is a paucity of literature evaluating the risk factors for disease-free survival (DFS) and overall survival (OS). The aim of this study was to identify the prognostic factors of DFS and OS in patients with NSCLC pIIA.We performed a retrospective review of 98 stage II patients (7th edition of the American Joint Committee on Cancer) who underwent lung resection from January 2005 to February 2011. Of these, 23 patients were excluded for this study because of loss of follow-up or different substage, and 75 patients with pIIA were included for further univariate and multivariate analysis. Risk factors for DFS and OS were analyzed, including age, gender, smoking history, operation method, histology, differential grade, visceral pleural invasion, angiolymphatic invasion, and metastatic N1 lymph node ratio (LNR).Of the 75 patients with pIIA NSCLC who were examined, 29 were female and 46 were male, with a mean age of 61.8 years (range: 34–83 years). The average tumor size was 3.188 cm (range: 1.10–6.0 cm). Under univariate analysis, angiolymphatic invasion and metastatic N1 LNR were risk factors for DFS (P = 0.011, P = 0.007). Under multivariate analysis, angiolymphatic invasion and metastatic N1 LNR were all independent risk factors for DFS, while adjuvant chemotherapy and higher metastatic N1 LNR were independent prognostic factors for OS.For patients with pIIA, higher metastatic N1 LNR and angiolymphatic invasion were related to poor DFS. In addition to DFS, higher metastatic N1 LNR was also a poor prognostic factor for OS rates and adjuvant therapy effectiveness. Clinical physicians should devise different postsurgical follow-up programs depending on these factors, especially for patients with high risk.

Invasive fungal infection among hematopoietic stem cell transplantation patients with mechanical ventilation in the intensive care unit

BackgroundInvasive fungal infection (IFI) is associated with high morbidity and high mortality in hematopoietic stem cell transplantation (HSCT) patientsThe purpose of this study was to assess the characteristics and outcomes of HSCT patients with IFIs who are undergoing MV at a single institution in Taiwan.MethodsWe performed an observational retrospective analysis of IFIs in HSCT patients undergoing mechanical ventilation (MV) in an intensive care unit (ICU) from the year 2000 to 2009. The characteristics of these HSCT patients and risk factors related to IFIs were evaluated. The status of discharge, length of ICU stay, date of death and cause of death were also recorded.ResultsThere were 326 HSCT patients at the Linkou Chang-Gung Memorial Hospital (Taipei, Taiwan) during the study period. Sixty of these patients (18%) were transferred to the ICU and placed on mechanical ventilators. A total of 20 of these 60 patients (33%) had IFIs. Multivariate analysis indicated that independent risk factors for IFI were admission to an ICU more than 40 days after HSCT, graft versus host disease (GVHD), and high dose corticosteroid (p < 0.01 for all). The overall ICU mortality rate was 88% (53 of 60 patients), and was not significantly different for patients with IFIs (85%) and those without IFIs (90%, p = 0.676).ConclusionThere was a high incidence of IFIs in HSCT patients requiring MV in the ICU in our study cohort. The independent risk factors for IFI are ICU admission more than 40 days after HSCT, GVHD, and use of high-dose corticosteroid.

Risk Factors and Possible Mechanisms of Superior Vena Cava Intravenous Port Malfunction

Objective:To identify the risk factors leading to catheter malfunction. Background:Reliable venous access is crucial for cancer patients. Malfunction of intravenous ports may lead to discontinuation of treatment and repeated interventions. We retrospectively reviewed the independent risk factors for catheter malfunction among patients receiving intravenous port implantations. Methods:A total of 1508 procedures were included from the calendar year 2006, and clinical data and chest plain films were analyzed. The patients were followed-up until June 30, 2010. For patients still alive, the last outpatient follow-up date was considered as the end point. For the remaining patients, the date of death or discharge against advice was considered as the end points. The risk factors for catheter malfunction were then evaluated. Results:The intervention-free periods of the malfunction group and nonmalfunction group were 317 and 413 days, respectively. Statistical analyses showed that the Nut-Catheter Angle was the only risk factor for catheter malfunction (P = 0.001). A logistic model also confirmed that the Nut-Catheter Angle was the only risk factor for catheter malfunction (P < 0.001). Valve tip catheters were not advantageous with regard to catheter malfunction prevention as compared to open tip catheters. Conclusions:A smaller Nut-Catheter Angle had a greater risk for catheter malfunction. Catheter impingement caused by inadequate pocket creation and port implantation lead to compromised catheter lumen and difficulty flushing. The possibility of retained blood and medications increased thin thrombotic biofilm formation and medication precipitation. Catheter malfunctions can be avoided by using proper surgical techniques and adequate maintenance.

The Treatment Results of a Standard Algorithm for Choosing the Best Entry Vessel for Intravenous Port Implantation

AbstractVascular cutdown and echo guide puncture methods have its own limitations under certain conditions. There was no available algorithm for choosing entry vessel. A standard algorithm was introduced to help choose the entry vessel location according to our clinical experience and review of the literature. The goal of this study is to analyze the treatment results of the standard algorithm used to choose the entry vessel for intravenous port implantation.During the period between March 2012 and March 2013, 507 patients who received intravenous port implantation due to advanced chemotherapy were included into this study. Choice of entry vessel was according to standard algorithm. All clinical characteristic factors were collected and complication rate and incidence were further analyzed.Compared with our clinical experience in 2006, procedure-related complication rate declined from 1.09% to 0.4%, whereas the late complication rate decreased from 19.97% to 3.55%. No more pneumothorax, hematoma, catheter kinking, fractures, and pocket erosion were identified after using the standard algorithm. In alive oncology patients, 98% implanted port could serve a functional vascular access to fit therapeutic needs.This standard algorithm for choosing the best entry vessel is a simple guideline that is easy to follow. The algorithm has excellent efficiency and can minimize complication rates and incidence.

Prognostic factors in resectable pathological N2 disease of non-small cell lung cancer.

Background: N2-positive non-small cell lung cancer (NSCLC) exhibits extremely low survival rates. The role of surgery in operable locally advanced N2 NSCLC remains controversial. In this study, we tried to analyze the role of surgery in resectable N2 NSCLC and the relationship between survival and clinico-pathologic factors from a pathologic point of view. Methods: 108 resectable pathologic N2-positive NSCLC patients, diagnosed from January 2005 to July 2012, were enrolled in this study. We retrospectively reviewed the medical records, image studies, and pathology reports to collect the clinico-pathologic factors in these patients. Results: Those who received lobectomy (p = 0.002) and had a metastatic lymph node ratio less than 0.4 (p = 0.01) had a better overall survival rate. In addition, our study also showed that perineural invasion may play a significant role in disease-free survival (p = 0.01) Conclusions: Metastatic lymph node ratio greater than 0.4 and non-anatomic resection were poor prognostic factors for disease-free survival. Anatomic resection for selected N2 patients may play a crucial role in the overall survival rate. Perineural invasion showed an adverse impact on disease-free survival, but further investigation is warranted.