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A flexible and wearable microsensor array is described for simultaneous multiplexed monitoring of heavy metals in human body fluids. Zn, Cd, Pb, Cu, and Hg ions are chosen as target analytes for detection via electrochemical square wave anodic stripping voltammetry (SWASV) on Au and Bi microelectrodes. The oxidation peaks of these metals are calibrated and compensated by incorporating a skin temperature sensor. High selectivity, repeatability, and flexibility of the sensor arrays are presented. Human sweat and urine samples are collected for heavy metal analysis, and measured results from the microsensors are validated through inductively coupled plasma mass spectrometry (ICP-MS). Real-time on-body evaluation of heavy metal (e.g., zinc and copper) levels in sweat of human subjects by cycling is performed to examine the change in concentrations with time. This platform is anticipated to provide insightful information about an individual's health state such as heavy metal exposure and aid the related clinical investigations.

In recent years, unmanned aerial vehicles (UAVs) have become a valuable platform for many applications, including communication networks. UAV-enabled wireless communication faces challenges in complex urban and dynamic environments. UAVs can suffer from power limitations and path losses caused by non-line-of-sight connections, which may hamper communication performance. To address these issues, reconfigurable intelligent surfaces (RIS) have been proposed as helpful technologies to enhance UAV communication networks. However, due to the high mobility of UAVs, complex channel environments, and dynamic RIS configurations, it is challenging to estimate the link quality of ground users. In this paper, we propose a link quality estimation model using a gated recurrent unit (GRU) to assess the link quality of ground users for a multi-user RIS-assisted UAV-enabled wireless communication system. Our proposed framework uses a time series of user channel data and RIS phase shift information to estimate the quality of the link for each ground user. The simulation results showed that the proposed GRU model can effectively and accurately estimate the link quality of ground users in the RIS-assisted UAV-enabled wireless communication network.

This study attempts to investigate the warpage behavior of a flip chip package-on-package (FCPoP) assembly during fabrication process. A process simulation framework that integrates thermal and mechanical finite element analysis (FEA), effective modeling and ANSYS element death-birth technique is introduced for effectively predicting the process-induced warpage. The mechanical FEA takes into account the viscoelastic behavior and cure shrinkage of the epoxy molding compound. In order to enhance the computational and modeling efficiency and retain the prediction accuracy at the same time, this study proposes a novel effective approach that combines the trace mapping method, rule of mixture and FEA to estimate the effective orthotropic elastic properties of the coreless substrate and core interposer. The study begins with experimental measurement of the temperature-dependent elastic and viscoelastic properties of the components in the assembly, followed by the prediction of the effective elastic properties of the orthotropic interposer and substrate. The predicted effective results are compared against the results of the ROM/analytical estimate and the FEA-based effective approach. Moreover, the warpages obtained from the proposed process simulation framework are validated by the in-line measurement data, and good agreement is presented. Finally, key factors that may influence process-induced warpage are examined via parametric analysis.

Sweat sensors targeting exercise or chemically induced sweat have shown promise for noninvasive health monitoring. Natural thermoregulatory sweat is an attractive alternative as it can be accessed during routine and sedentary activity without impeding user lifestyles and potentially preserves correlations between sweat and blood biomarkers. We present simple glove-based sensors to accumulate natural sweat with minimal evaporation, capitalizing on high sweat gland densities to collect hundreds of microliters in just 30 min without active sweat stimulation. Sensing electrodes are patterned on nitrile gloves and finger cots for in situ detection of diverse biomarkers, including electrolytes and xenobiotics, and multiple gloves or cots are worn in sequence to track overarching analyte dynamics. Direct integration of sensors into gloves represents a simple and low-overhead scheme for natural sweat analysis, enabling sweat-based physiological monitoring to become practical and routine without requiring highly complex or miniaturized components for analyte collection and signal transduction., (Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).)

The tobacco epidemic is a public health threat that has taken a heavy toll of lives around the globe each year. Smoking affects both the smokers and those who are exposed to secondhand smoke, and careful tracking of exposure can be key to mitigating the potential hazards. For smokers, the variation of chemical compositions between commercial cigarettes has led to ambiguity in estimating the health risks, both for active smokers and others involuntarily exposed to tobacco smoke and byproducts. In this regard, sweat possesses an attractive opportunity to monitor smoke exposure due to sweat's abundance in biomolecules and its great accessibility. Here, we present a wearable sweat band to monitor nicotine, a prominent ingredient in cigarettes, as a viable way to quantitatively assess a wearer's exposure to smoking. Both smokers and normal subjects are tested to demonstrate the use of this device for smoke-related health monitoring. Our results exhibit confirmable and elevated nicotine levels in sweat for subjects inhaling cigarette smoke. This continuous and personalized sweat sensing device is leverage to monitor smoke pollution for a potentially broad population.

Sweat sensors introduced in recent years have targeted a variety of sweat features and biomarkers for non-invasive health monitoring. Amongst these targets, reliable monitoring of sweat rate is crucial due to its modulation of sweat analyte concentrations and its intrinsic significance to numerous medical and physiological health conditions. Here we present a sweat rate sensor structure comprising of electrodes with interdigitated fingers in a microfluidic channel. Each time the accumulating sweat impinges on an electrode finger, the sensor reports a jump in admittance that can be simply and efficiently counted to estimate sweat rate, overcoming selectivity limitations of previously reported sweat rate sensors. We further integrate an impedimetric sensor for measuring total ionic charge concentration and an electrochemical Na + sensor, together creating a multi-modal system for analyzing fluid and electrolyte secretion. We demonstrate how low analyte diffusion rates through this microfluidic device allow for multi-purpose sensor function, including utilizing the sweat rate sensor signal to corroborate total ionic sensor measurements. This cross-verification capability ensures data integrity in real time, satisfying a vital consideration for personalized healthcare technologies. We use the presented patch for continuous analysis of sweat rate, total ionic charge concentration, and Na + concentration during exercise, while demonstrating how multi-modal cross-verification brings new trust to sensor readings.

Levodopa is the standard medication clinically prescribed to patients afflicted with Parkinson's disease. In particular, the monitoring and optimization of levodopa dosage are critical to mitigate the onset of undesired fluctuations in the patients' physical and emotional conditions such as speech function, motor behavior, and mood stability. The traditional approach to optimize levodopa dosage involves evaluating the subjects' motor function, which has many shortcomings due to its subjective and limited quantifiable nature. Here, we present a wearable sweat band on a nanodendritic platform that quantitatively monitors levodopa dynamics in the body. Both stationary iontophoretic induction and physical exercise are utilized as our methods of sweat extraction. The sweat band measures real-time pharmacokinetic profiles of levodopa to track the dynamic response of the drug metabolism. We demonstrated the sweat band's functionalities on multiple subjects with implications toward the systematic administering of levodopa and routine management of Parkinson's disease.

Recent technological advancements in wearable sensors have made it easier to detect sweat components, but our limited understanding of sweat restricts its application. A critical bottleneck for temporal and regional sweat analysis is achieving uniform, high-throughput fabrication of sweat sensor components, including microfluidic chip and sensing electrodes. To overcome this challenge, we introduce microfluidic sensing patches mass fabricated via roll-to-roll (R2R) processes. The patch allows sweat capture within a spiral microfluidic for real-time measurement of sweat parameters including [Na + ], [K + ], [glucose], and sweat rate in exercise and chemically induced sweat. The patch is demonstrated for investigating regional sweat composition, predicting whole-body fluid/electrolyte loss during exercise, uncovering relationships between sweat metrics, and tracking glucose dynamics to explore sweat-to-blood correlations in healthy and diabetic individuals. By enabling a comprehensive sweat analysis, the presented device is a crucial tool for advancing sweat testing beyond the research stage for point-of-care medical and athletic applications.

Wearable devices for health monitoring and fitness management have foreseen a rapidly expanding market, especially those for noninvasive and continuous measurements with real-time display that provide practical convenience and eliminated safety/infection risks. Herein, a self-powered and fully integrated smartwatch that consists of flexible photovoltaic cells and rechargeable batteries in the forms of a "watch strap", electrochemical glucose sensors, customized circuits, and display units integrated into a "dial" platform is successfully fabricated for real-time and continuous monitoring of sweat glucose levels. The functionality of the smartwatch, including sweat glucose sensing, signal processing, and display, can be supported with the harvested/converted solar energy without external charging devices. The Zn-MnO 2 batteries serve as intermediate energy storage units and the utilization of aqueous electrolytes eliminated safety concerns for batteries, which is critical for wearable devices. Such a wearable system in a smartwatch fashion realizes integration of energy modules with self-powered capability, electrochemical sensors for noninvasive glucose monitoring, and in situ and real-time signal processing/display in a single platform for the first time. The as-fabricated fully integrated and self-powered smartwatch also provides a promising protocol for statistical study and clinical investigation to reveal correlations between sweat compositions and human body dynamics.

As recent developments in noninvasive biosensors spearhead the thrust toward personalized health and fitness monitoring, there is a need for high throughput, cost-effective fabrication of flexible sensing components. Toward this goal, we present roll-to-roll (R2R) gravure printed electrodes that are robust under a range of electrochemical sensing applications. We use inks and electrode morphologies designed for electrochemical and mechanical stability, achieving devices with uniform redox kinetics printed on 150 m flexible substrate rolls. We show that these electrodes can be functionalized into consistently high performing sensors for detecting ions, metabolites, heavy metals, and other small molecules in noninvasively accessed biofluids, including sensors for real-time, in situ perspiration monitoring during exercise. This development of robust and versatile R2R gravure printed electrodes represents a key translational step in enabling large-scale, low-cost fabrication of disposable wearable sensors for personalized health monitoring applications.

Drug monitoring plays crucial roles in doping control and precision medicine. It helps physicians tailor drug dosage for optimal benefits, track patients' compliance to prescriptions, and understand the complex pharmacokinetics of drugs. Conventional drug tests rely on invasive blood draws. While urine and sweat are attractive alternative biofluids, the state-of-the-art methods require separate sample collection and processing steps and fail to provide real-time information. Here, a wearable platform equipped with an electrochemical differential pulse voltammetry sensing module for drug monitoring is presented. A methylxanthine drug, caffeine, is selected to demonstrate the platform's functionalities. Sweat caffeine levels are monitored under various conditions, such as drug doses and measurement time after drug intake. Elevated sweat caffeine levels upon increasing dosage and confirmable caffeine physiological trends are observed. This work leverages a wearable sweat sensing platform toward noninvasive and continuous point-of-care drug monitoring and management., (© 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Wearable sweat sensing is a rapidly rising research area driven by its promising potential in health, fitness, and diagnostic applications. Despite the growth in the field, major challenges in relation to sweat metrics remain to be addressed. These challenges include sweat rate monitoring for its complex relation with sweat compositions and sweat sampling for sweat dynamics studies. In this work, we present a flexible microfluidic sweat sensing patch that enhances real-time electrochemical sensing and sweat rate analysis via sweat sampling. The device contains a spiral-patterned microfluidic component that is embedded with ion-selective sensors and an electrical impedance-based sweat rate sensor on a flexible plastic substrate. The patch is enabled to autonomously perform sweat analysis by interfacing the sensing component with a printed circuit board that is capable of on-site signal conditioning, analysis, and transmission. Progressive sweat flow in the microfluidic device, governed by the pressure induced by the secreted sweat, enhances sweat sampling and electrochemical detection via a defined sweat collection chamber and a directed sweat route. The characteristic of the sweat rate sensor is validated through a theoretical simulation, and the precision and accuracy of the flow rate is verified with a commercial syringe pump and a Macroduct sweat collector. On-body simultaneous monitoring of ion (H + , Na + , K + , Cl - ) concentration and sweat rate is also demonstrated for sensor functionality. This sweat sensing patch provides an integrated platform for a comprehensive sweat secretion analysis and facilitates physiological and clinical investigations by closely monitoring interrelated sweat parameters.

Objectives: The classification of pathological tumor-node-metastasis (pTNM) staging of gastric cancer was revised in the 8th American Joint Committee on Cancer (AJCC) edition. The major revision was the separation of pN3a and pN3b in the pTNM staging. The current study evaluated the prognostic impact of this change., Methods: A total of 1,517 patients who underwent curative surgery for gastric cancer with a retrieved lymph node number ≥15 at our institution from January 1995 to December 2011 were enrolled. Survival was compared for the disease classified according to both the 7th and 8th editions., Results: After separation of pN3a and pN3b in the pTNM stage definition, the 8th edition still provides significant survival differences between each stage. The multivariate analysis demonstrated that the pTNM stage in both the 7th and 8th editions was an independent prognostic factors of overall survival and disease-free survival. The 8th edition has a better homogeneity than the 7th edition with a significantly higher likelihood ratio chi-square test. Regarding the OS and DFS, the time-dependent receiver operating characteristic (ROC) curves of the two staging systems are almost overlapping, indicating that the prognostic performance is comparable between the two staging systems., Conclusions: Both the 7th and 8th edition-based stages are independent prognostic factors for gastric cancer. The 8th edition has a better homogeneity than the 7th edition; the 8th edition provides discriminant survival differences among each pTNM stage that are comparable to those in the 7th edition.

Flexible pressure sensors have many potential applications in wearable electronics, robotics, health monitoring, and more. In particular, liquid-metal-based sensors are especially promising as they can undergo strains of over 200% without failure. However, current liquid-metal-based strain sensors are incapable of resolving small pressure changes in the few kPa range, making them unsuitable for applications such as heart-rate monitoring, which require a much lower pressure detection resolution. In this paper, a microfluidic tactile diaphragm pressure sensor based on embedded Galinstan microchannels (70 µm width × 70 µm height) capable of resolving sub-50 Pa changes in pressure with sub-100 Pa detection limits and a response time of 90 ms is demonstrated. An embedded equivalent Wheatstone bridge circuit makes the most of tangential and radial strain fields, leading to high sensitivities of a 0.0835 kPa -1 change in output voltage. The Wheatstone bridge also provides temperature self-compensation, allowing for operation in the range of 20-50 °C. As examples of potential applications, a polydimethylsiloxane (PDMS) wristband with an embedded microfluidic diaphragm pressure sensor capable of real-time pulse monitoring and a PDMS glove with multiple embedded sensors to provide comprehensive tactile feedback of a human hand when touching or holding objects are demonstrated., (© 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Real-time detection of basic physiological parameters such as blood pressure and heart rate is an important target in wearable smart devices for healthcare. Among these, the core body temperature is one of the most important basic medical indicators of fever, insomnia, fatigue, metabolic functionality, and depression. However, traditional wearable temperature sensors are based upon the measurement of skin temperature, which can vary dramatically from the true core body temperature. Here, we demonstrate a three-dimensional (3D) printed wearable "earable" smart device that is designed to be worn on the ear to track core body temperature from the tympanic membrane (i.e., ear drum) based on an infrared sensor. The device is fully integrated with data processing circuits and a wireless module for standalone functionality. Using this smart earable device, we demonstrate that the core body temperature can be accurately monitored regardless of the environment and activity of the user. In addition, a microphone and actuator are also integrated so that the device can also function as a bone conduction hearing aid. Using 3D printing as the fabrication method enables the device to be customized for the wearer for more personalized healthcare. This smart device provides an important advance in realizing personalized health care by enabling real-time monitoring of one of the most important medical parameters, core body temperature, employed in preliminary medical screening tests.

Homeostasis of ionized calcium in biofluids is critical for human biological functions and organ systems. Measurement of ionized calcium for clinical applications is not easily accessible due to its strict procedures and dependence on pH. pH balance in body fluids greatly affects metabolic reactions and biological transport systems. Here, we demonstrate a wearable electrochemical device for continuous monitoring of ionized calcium and pH of body fluids using a disposable and flexible array of Ca(2+) and pH sensors that interfaces with a flexible printed circuit board. This platform enables real-time quantitative analysis of these sensing elements in body fluids such as sweat, urine, and tears. Accuracy of Ca(2+) concentration and pH measured by the wearable sensors is validated through inductively coupled plasma-mass spectrometry technique and a commercial pH meter, respectively. Our results show that the wearable sensors have high repeatability and selectivity to the target ions. Real-time on-body assessment of sweat is also performed, and our results indicate that calcium concentration increases with decreasing pH. This platform can be used in noninvasive continuous analysis of ionized calcium and pH in body fluids for disease diagnosis such as primary hyperparathyroidism and kidney stones.

Label-free cell analysis is essential to personalized genomics, cancer diagnostics, and drug development as it avoids adverse effects of staining reagents on cellular viability and cell signaling. However, currently available label-free cell assays mostly rely only on a single feature and lack sufficient differentiation. Also, the sample size analyzed by these assays is limited due to their low throughput. Here, we integrate feature extraction and deep learning with high-throughput quantitative imaging enabled by photonic time stretch, achieving record high accuracy in label-free cell classification. Our system captures quantitative optical phase and intensity images and extracts multiple biophysical features of individual cells. These biophysical measurements form a hyperdimensional feature space in which supervised learning is performed for cell classification. We compare various learning algorithms including artificial neural network, support vector machine, logistic regression, and a novel deep learning pipeline, which adopts global optimization of receiver operating characteristics. As a validation of the enhanced sensitivity and specificity of our system, we show classification of white blood T-cells against colon cancer cells, as well as lipid accumulating algal strains for biofuel production. This system opens up a new path to data-driven phenotypic diagnosis and better understanding of the heterogeneous gene expressions in cells.

Background: Adenosquamous carcinoma (ASC) is a rare disease involving various organs, yet there are no large-scale population-based comparative studies on ASC among different organs., Methods: The incidence and overall survival of ASC among various organs in cases diagnosed in Taiwan from January 1, 2003 to December 31, 2010 were calculated and compared using data from the Taiwan Cancer Registry (TCR). The various organs were classified and divided into three different systems: the female reproductive, respiratory, and alimentary systems. Survival analysis were also compared among 30,850 patients diagnosed as ASC, adenocarcinoma (AC) or squamous cell carcinoma (SCC) in organs with frequent ASC., Results: During the study period, a total of 576 ASC cases were diagnosed in Taiwan. The most common primary system was respiratory (73.8%), followed by alimentary (16.2%) and female reproductive (10%). The overall survival were significantly higher for cases involving the female reproductive system, followed by the respiratory and alimentary systems (P = 0.016). The median overall survival were worse in males than females for cases involving the respiratory system (22.4 vs. 31.8 months, P = 0.044). Multivariate analysis showed that age ≧ 65, more advanced T and N categories were independent unfavorable prognostic factors of overall survival in ASC. ASC histology is an independent unfavorable prognostic factor compared with AC and SCC., Conclusions: ASC at an old age and more advanced T and N categories were found to be associated with a poor prognosis.

Background: Ultramarathon is a high endurance exercise associated with a wide range of exercise-related problems, such as acute kidney injury (AKI). Early recognition of individuals at risk of AKI during ultramarathon event is critical for implementing preventative strategies., Objectives: To investigate the impact of speed variability to identify the exercise-related acute kidney injury anticipatively in ultramarathon event., Methods: This is a prospective, observational study using data from a 100 km ultramarathon in Taipei, Taiwan. The distance of entire ultramarathon race was divided into 10 splits. The mean and variability of speed, which was determined by the coefficient of variation (CV) in each 10 km-split (25 laps of 400 m oval track) were calculated for enrolled runners. Baseline characteristics and biochemical data were collected completely 1 week before, immediately post-race, and one day after race. The main outcome was the development of AKI, defined as Stage II or III according to the Acute Kidney Injury Network (AKIN) criteria. Multivariate analysis was performed to determine the independent association between variables and AKI development., Results: 26 ultramarathon runners were analyzed in the study. The overall incidence of AKI (in all Stages) was 84.6% (22 in 26 runners). Among these 22 runners, 18 runners were determined as Stage I, 4 runners (15.4%) were determined as Stage II, and none was in Stage III. The covariates of BMI (25.22 ± 2.02 vs. 22.55 ± 1.96, p = 0.02), uric acid (6.88 ± 1.47 vs. 5.62 ± 0.86, p = 0.024), and CV of speed in specific 10-km splits (from secondary 10 km-split (10th - 20th km-split) to 60th - 70th km-split) were significantly different between runners with or without AKI (Stage II) in univariate analysis and showed discrimination ability in ROC curve. In the following multivariate analysis, only CV of speed in 40th - 50th km-split continued to show a significant association to the development of AKI (Stage II) (p = 0.032)., Conclusions: The development of exercise-related AKI was not infrequent in the ultramarathon runners. Because not all runners can routinely receive laboratory studies after race, variability of running speed (CV of speed) may offer a timely and efficient tool to identify AKI early during the competition, and used as a surrogate screening tool, at-risk runners can be identified and enrolled into prevention trials, such as adequate fluid management and avoidance of further NSAID use.

Background: Brain metastasis is a major complication of breast cancer. This study aimed to analyze the effect of age and biological subtype on the risk and timing of brain metastasis in breast cancer patients., Patients and Methods: We identified subtypes of invasive ductal carcinoma of the breast by determining estrogen receptor, progesterone receptor and HER2 status. Time to brain metastasis according to age and cancer subtype was analyzed by Cox proportional hazard analysis., Results: Of the 2248 eligible patients, 164 (7.3%) developed brain metastasis over a median follow-up of 54.2 months. Age 35 or younger, HER2-enriched subtype, and triple-negative breast cancer were significant risk factors of brain metastasis. Among patients aged 35 or younger, the risk of brain metastasis was independent of biological subtype (P = 0.507). Among patients aged 36-59 or >60 years, those with triple-negative or HER2-enriched subtypes had consistently increased risk of brain metastasis, as compared with those with luminal A tumors. Patients with luminal B tumors had higher risk of brain metastasis than luminal A only in patients >60 years., Conclusions: Breast cancer subtypes are associated with differing risks of brain metastasis among different age groups. Patients age 35 or younger are particularly at risk of brain metastasis independent of biological subtype.

Background: Although diabetes mellitus (DM) can be treated with islet transplantation, a scarcity of donors limits the utility of this technique. This study investigated whether human mesenchymal stem cells (MSCs) from umbilical cord could be induced efficiently to differentiate into insulin-producing cells. Secondly, we evaluated the effect of portal vein transplantation of these differentiated cells in the treatment of streptozotocin-induced diabetes in rats., Methods: MSCs from human umbilical cord were induced in three stages to differentiate into insulin-producing cells and evaluated by immunocytochemistry, reverse transcriptase, and real-time PCR, and ELISA. Differentiated cells were transplanted into the liver of diabetic rats using a Port-A catheter via the portal vein. Blood glucose levels were monitored weekly., Results: Human nuclei and C-peptide were detected in the rat liver by immunohistochemistry. Pancreatic β-cell development-related genes were expressed in the differentiated cells. C-peptide release was increased after glucose challenge in vitro. Furthermore, after transplantation of differentiated cells into the diabetic rats, blood sugar level decreased. Insulin-producing cells containing human C-peptide and human nuclei were located in the liver., Conclusion: Thus, a Port-A catheter can be used to transplant differentiated insulin-producing cells from human MSCs into the portal vein to alleviate hyperglycemia among diabetic rats.

Background & Problems: Detailed descriptions of nursing shift tasks are necessary to achieve comprehensive nursing care. The 22 cases of postoperative recovery ward error reported by our unit included chest tube obstructions, lost dentures and other nursing issues. To improve patient health and nurse shift quality, our unit established an ad hoc group to collect data helpful to overcoming problems attributable to nurse shift changes. We aimed to better nursing care by facilitating individualized patient care and avoiding accidents detrimental to patient safety., Purpose: This project was designed to raise the rate of 100% completion of nursing shift-change tasks to 91% of postoperative recovery room nurses., Resolution: Newly revised operating standards regarding the recovery period after anesthesia established guidelines for a regular audit mechanism and in-service education programs for recovery room shift tasks., Result: Full completion of shift tasks in the postoperative recovery room improved from 73.5% to 98.6% of nurses., Conclusion: Comprehensive completion of postoperative nursing shift-change tasks increases communication between team members, provides continuous care for patients, and enhances overall nursing care quality.

Background: Only a small proportion of patients with end-stage renal disease can receive kidney transplants because of insufficiency of kidney donors in Taiwan. Hospitals compete with each other for kidney transplant surgeries. This study examined the association between hospital surgical volume of kidney transplants and patients' outcomes and utilizations., Methods: Claims data of all kidney transplants between 1996 and 2003 were retrieved from the National Health Insurance Research Database for analysis. Every kidney recipient was followed up for 3 years until the end of 2006. Hospitals were classified as high-surgical-volume hospitals (HSVHs) if their total number of kidney transplants was 72 or more between 1996 and 2003; otherwise, they were grouped into the low-surgical-volume hospitals (LSVHs). The differences in quality (infection rate, graft rejection rate, readmission rate, mortality, and survival rates of patients and transplanted grafts at 1, 2, and 3 years after surgery) and cost (length of stay, total transplant cost, and annual medical cost for 3 years) of kidney transplants were examined between the two groups., Results: Totally, 1,060 kidney transplants were analyzed, 77% of which were conducted at 6 of 29 qualified hospitals. Compared with those performed at LSVHs, transplant surgeries at HSVHs were associated with lower bacteria (35.1% vs. 48.8%, p<0.001), fungus (0.2% vs. 1.3%, p=0.008), and cytomegalovirus (1.2% vs. 4.6%, p=0.003) infection; lower mortality (1.1% vs. 5.0%, p<0.001); and higher 1-, 2-, and 3-year survival rates for patients (96.3%, 94.1%, 93.5% vs. 91.2%, 87.1%, 85.4%, respectively, p<0.01) and for transplanted grafts (89.5%, 81.0%, 80.5% vs. 85.8%, 74.6%, 73.3%, respectively, p<0.015). The transplant cost was lower for HSVHs than for LSVHs (New Taiwan $221,977 vs. New Taiwan $257,992, p=0.018)., Conclusion: Seventy-seven percent of kidney transplant surgeries were concentrated at six hospitals in Taiwan. There were significant differences in quality and cost between HSVHs and LSVHs. We suggest adopting volume-based strategies for nonurgent kidney transplants., (Copyright © 2011. Published by Elsevier B.V.)

Background/aims: Signet ring cell carcinoma and mucinous carcinoma are mucin-producing gastric cancers. Their clinicopathological difference was obscure., Methodology: From December 1987 to July 2005, a total of 1612 gastric cancer patients received curative surgery, 128 patients with signet ring cell carcinoma and 48 with mucinous carcinoma were enrolled in this study. Clinicopathological data were compared between the two groups., Results: Early stage (stage I and II) patients with mucinous carcinoma were associated with more male predominant (p = 0.002), larger tumor size (p = 0.020), deeper cancer invasion (p < 0.001), and a worse 5-year overall survival (63.6% vs 88.2%, p = 0.012) than those with signet ring cell carcinoma. There was no significant difference between the two groups with advanced stage in 5-year overall survival. There is no significant difference in the initial recurrence pattern between the two groups., Conclusions: Patients with mucinous carcinoma had different biological behaviors with those with signet ring cell carcinoma, in particular early stage, hence had a worse survival.

Background: A comprehensive study of carcinoid tumors from United States-based databases indicated that the small intestine, colon, rectum, and bronchopulmonary system are common locations for carcinoid tumors. In addition, certain carcinoid tumors, such as rectal carcinoids, appeared to be overrepresented in nonwhite populations in the United States. High frequencies of associated noncarcinoid malignancies were reported in some articles. The objective of the current study was to address the organ distribution, frequency of metastasis, and survival rates of carcinoid tumors and the associated noncarcinoid tumors in Taiwanese, Asian populations., Methods: Two hundred twenty-eight patients with carcinoid tumors were identified and evaluated from the surgical pathology files and medical records of the Veterans General Hospital, Taipei, Taiwan from January 1970 to December 2005., Results: In 228 carcinoid tumors that were analyzed, the rectum (60.5%) was the most common location followed by the lung (20.2%) and the thymus (6.6%). Metastatic lesions were demonstrated in 16.2% of patients. Disease extent was associated with survival. The 5-year survival rates for patients with localized, regional metastatic, and distant metastatic disease were 94.1%, 49.1%, and 0%, respectively (P< .001). Associated noncarcinoid malignancies were noted in 14% of patients with carcinoids, mainly in the gastrointestinal tract (52.9%), lung, and genitourinary system., Conclusions: A different organ distribution of carcinoids was observed in Taiwanese patients, who had with significantly more carcinoids located in the rectum and thymus compared with patients in Western countries. The patients with carcinoids in the current study had a high possibility of developing associated, noncarcinoid neoplasms. Surveillance of the colon, stomach, lung, and genitourinary system for second malignant tumors is recommended.

Objectives: Pancreatic exocrine insufficiency has been reported to be more common in pancreaticogastrostomy (PG) than in pancreaticojejunostomy (PJ) after pancreaticoduodenectomy (PD). This study aimed to evaluate the long-term outcome after PD between these 2 groups., Methods: We evaluated the long-term functional status of 42 surviving patients diagnosed with periampullary lesions who underwent PJ or PG after PD and followed up for more than 1 year. Among these, 23 patients underwent PJ and 19 patients underwent PG. To compare the 2 groups, we analyzed the (1) pancreatic exocrine insufficiency by questioning the presence or absence of steatorrhea, (2) pancreatic endocrine function by measuring glycohemoglobin A1c, fasting blood glucose, and history of new-onset diabetes, (3) nutritional status by measuring serum total protein, albumin, cholesterol, and triglyceride, (4) gastric emptying time, (5) panendoscopic findings, (6) changes of pancreatic duct diameter by computed tomography, and (7) relaparotomy rate., Results: The mean follow-up time for PG and PJ were 37 +/- 23 and 103 +/- 52 months, respectively (P < 0.05). A total of 52.4% patients developed pancreatic exocrine insufficiency, and 11.9% had new-onset diabetes. There was no significant difference between PJ and PG groups. A significantly improved postoperative nutritional state regarding serum total protein and albumin were noticed in both groups. There was no significant difference in terms of gastric emptying time, positive panendoscopic findings, and changes in pancreatic duct diameter. The pancreatic remnant-related relaparotomy rate was higher in the PJ group as compared with the PG group (17.4% vs 0%; P = 0.056)., Conclusions: There is no significant difference in pancreatic exocrine or endocrine insufficiency, gastric emptying time, and positive panendoscopic findings between PJ and PG. Pancreaticojejunostomy was associated with a higher pancreatic remnant-related relaparotomy rate; however, because of a shorter follow-up in the PG group, a continuous long-term follow-up is still needed.

Background: It is well documented that a daily oral dose of 0.625 mg of conjugated equine estrogen or 1-2 mg of 17beta-estradiol is needed to prevent postmenopausal bone loss. Recent studies have indicated that a lower dose of estrogen maybe as effective in maintaining bone mass. The purpose of this study was to evaluate the effects of 3 dosages of transdermally administered 17beta-estradiol gel in postmenopausal women stratified by oophorectomy and natural menopause., Methods: One hundred and twenty postmenopausal women were randomly selected to form 4 groups. Three groups of women were treated with a transdermal administration of estradiol gel at a daily dosage of 1.25, 2.5 and 5.0 g (containing 0.75, 1.5, and 3 mg of 17beta-estradiol/day), respectively. The 4th group of women, receiving estriol 2 mg/day p.o., was studied concurrently as a control. Bone mineral density was measured by quantitative computed tomography of the vertebrae from T12 to L3 at baseline, then at 6-month intervals for 1 year., Results: Women in all groups receiving 17beta-estradiol gel obtained a significant increase in bone mass, with the exception of the 1.25 g/day group, which showed a minimal increment at the 6-month period, compared with the control group. Comparisons of the increments in bone mass after estrogen therapy for both natural and surgical menopausal subjects found that there was a more prominent response in surgical menopausal women receiving a dosage of 2.5 g/day., Conclusion: Estradiol gel at the dosage of 1.25 g/day, equivalent to 17beta-estradiol 0.75 mg/day, effectively prevented bone loss in postmenopausal women after a 12-month treatment period. The therapeutic effect of estradiol gel on bone mass was more prominent in the surgical menopausal groups at the dosage of 2.5 g/day. The atrophic ovaries may therefore play a crucial role in the subsequent decades of postmenopausal women.

Background and Aim: Obstruction of the lumen of the appendix is the major cause of appendicitis. Tumors could obstruct this lumen and cause appendicitis in the elderly. The association between appendicitis and colon cancer has not been sufficiently investigated, and this study was designed to clarify this association., Methods: This was a retrospective study. Patients diagnosed with acute appendicitis from January 1998 to December 2003 at the Taipei Veterans General Hospital were surveyed. Patients found to have colon cancers immediately or subsequently after appendectomy were included and analyzed., Results: A total of 1873 patients were diagnosed as having appendicitis of whom 16 were found to have colon cancer. The incidence of appendicitis associated with colon cancer was 0.85%. The time from appendectomy to the recognition of colonic cancer was at a median delay of 5.8 months. From the Taiwan Cancer Research Annual Report, the incidence of colon cancer was 31.91/100,000 in the year 2000. The odds ratio of colon cancer incidence had a 38.5-fold increase among patients older than 40 with acute appendicitis., Conclusions: In patients over 40 years who present with symptoms of acute appendicitis the possibility of a coexistent colonic neoplasm should always be kept in mind. These patients should undergo colonoscopy 6 weeks after surgery to exclude the possibility of a coexistent colorectal cancer.

Studies from this laboratory (Mayer et al. (1986) Biochim. Biophys. Acta 857, 123-126) have shown that doxorubicin can be accumulated into liposomal systems in response to transmembrane pH gradients (inside acidic). Here, detailed characterizations of the drug uptake and retention properties of these systems are performed. It is shown that for egg phosphatidylcholine (EPC) vesicles (mean diameter of 170 nm) exhibiting transmembrane pH gradients (inside acidic) doxorubicin can be sequestered into the interior aqueous compartment to achieve drug trapping efficiencies in excess of 98% and drug-to-lipid ratios of 0.36:1 (mol/mol). Drug-to-lipid ratios as high as 1.7:1 (mol/mol) can be obtained under appropriate conditions. Lower drug-to-lipid ratios are required to achieve trapping efficiencies in excess of 98% for smaller (less than or equal to 100 nm) systems. Doxorubicin trapping efficiencies and uptake capacities are related ito maintenance of the transmembrane pH gradient during encapsulation as well as the interaction between doxorubicin and entrapped citrate. This citrate-doxorubicin interaction increases drug uptake levels above those predicted by the Henderson-Hasselbach relationship. Increased drug-to-lipid ratios and trapping efficiencies are observed for higher interior buffering capacities. Retention of a large transmembrane pH gradient (greater than 2 units) after entrapment reduces the rate of drug leakage from the liposomes. For example, EPC/cholesterol (55:45, mol/mol) liposomal doxorubicin systems can be achieved which released less than 5% of encapsulated doxorubicin (drug-to-lipid molar ratio = 0.33:1) over 24 h at 37 degrees C. This pH gradient-dependent encapsulation technique is extremely versatile, and well characterized liposomal doxorubicin preparations can be generated to exhibit a wide range of properties such as vesicle size, lipid composition, drug-to-lipid ratio and drug release kinetics. This entrapment procedure therefore appears well suited for use in therapeutic applications. Finally, a rapid colorimetric test for determining the amount of unencapsulated doxorubicin in liposomal systems is described.

We have shown previously that transmembrane proton gradients can be used to efficiently accumulate biogenic amines [M.B. Bally et al. (1988) Chem. Phys. Lipids 47, 97-107] and doxorubicin [L.D. Mayer, M.B. Bally and P.R. Cullis (1986) Biochim. Biophys. Acta 857, 123-126] to high concentrations within liposomes. To determine the generality of this loading procedure, representative drugs from a variety of different classes (antineoplastics, local anaesthetics, antihistamines, etc.) were examined as to their ability to redistribute in response to a proton gradient. While the majority of drugs examined, all of which are weak bases, were accumulated by large unilamellar vesicles exhibiting a pH gradient (interior acid) the extent of uptake varied considerably between different pharmaceuticals. These differences are discussed in the context of various factors which will likely influence drug accumulation including its membrane/water partition coefficient and its solubility in the intravesicular medium.

The effects of vesicle size, lipid composition, and drug-to-lipid ratio on the biological activity of liposomal doxorubicin in mice have been investigated using a versatile procedure for encapsulating doxorubicin inside liposomes. In this procedure, vesicles exhibiting transmembrane pH gradients (acidic inside) were employed to achieve drug trapping efficiencies in excess of 98%. Drug-to-lipid ratios as high as 0.3:1 (wt:wt) could be obtained in a manner that is relatively independent of lipid composition and vesicle size. Egg phosphatidylcholine (EPC)/cholesterol (55:45; mol/mol) vesicles sized through filters with a 200-nm pore size and loaded employing transmembrane pH gradients to achieve a doxorubicin-to-lipid ratio of 0.3:1 (wt/wt) increased the LD50 of free drug by approximately twofold. Removing cholesterol or decreasing the drug-to-lipid ratio in EPC/cholesterol preparations led to significant decreases in the LD50 of liposomal doxorubicin whereas, the LD50 increased 4- to 6-fold when distearoylphosphatidylcholine was substituted for EPC. The results suggest that the stability of liposomally entrapped doxorubicin in the circulation is an important factor in the toxicity of this drug in liposomal form. In contrast, the antitumor activity of liposomal doxorubicin is not influenced dramatically by alterations in lipid composition. Liposomal doxorubicin preparations of EPC, EPC/cholesterol (55:45; mol:mol), EPC/egg phosphatidylglycerol (EPG)/cholesterol (27.5:27.5:45; mol:mol), and distearoylphosphatidylcholine/cholesterol (55:45; mol:mol) all demonstrated similar efficacy to that of free drug when given at doses of 20 mg/kg and below. Higher dose levels of the less toxic formulations could be administered, leading to enhanced increases in life span (ILS) values. Variations in vesicle size, however, strongly influenced the antitumor activity of liposomal doxorubicin. At a dose of 20 mg/kg, large EPC/cholesterol systems are significantly less effective than free drug (with ILS values of 65% and 145%, respectively). In contrast, small systems sized through filters with a 100-nm pore size are more effective than free drug, resulting in an ILS of 375% and a 30% long term (greater than 60 days) survival rate when administered at a dose of 20 mg/kg. Similar size-dependent effects are observed for distearoylphosphatidylcholine/cholesterol systems.