Visualization of lower extremity lymphedema in the same cohort using 99mTc-human serum albumin and 99mTc-phytate lymphoscintigraphy with SPECT-CT.

Lymphoscintigraphy with single-photon emission computed tomography (SPECT-CT) is useful in diagnosing lymphedema. However, there are multiple timings, techniques, and tracers utilized worldwide without any comparison. We examined and compared the image clarity with two different radiotracers, 99mTc human serum albumin (HSA) and 99mTc phytate (phytate), in the same patients. The study retrospectivity examined 46 limbs of 36 patients who underwent lymphoscintigraphy using HSA and phytate from January 2013 to September 2018. Tracer accumulation in the lymph nodes, linear pattern (LP), and dermal backflow (DBF) were qualitatively analyzed; contrast-to-noise ratios (CNR) of DBF and standardized uptake value ratio (SUVR) of LP were also quantitatively analyzed. Neither lymph node accumulation nor DBF identification showed significant difference. However, a significant difference was observed between the LP identification of the unaffected (p<0.001) and affected sides (p<0.001). On quantitative evaluation, CNR and SUVR of LP was significantly higher with HSA than with phytate (p<0.001). SUVR of LP was also significantly higher with HSA than with phytate in both unaffected (p=0.002) and affected (p=0.005) sides. Overall, images acquired with HSA were clearer than that with phytate, and the identification of LP was particularly better with HSA than with phytate. Thus, lymphoscintigraphy using HSA is preferred over phytate for both diagnosis and evaluation of disease severity and surgical site selection.

Design of microfluidic channels to prevent negative filtration in implantable hemofiltration devices.

In order to improve the quality of life of dialysis patients, our group have been developing an implantable hemofiltration device (IHFD) composed of multiple layers of dialysis membranes and microfluidic channels. To improve the hemodialysis performance of IHFD, preventing the negative filtration, which is caused by the oncotic pressure of blood, is mandatory. In this study, we fabricated IHFDs with five different microchannel designs and experimentally investigated the performance of each device in in vitro experiment. In addition, the successful IHFD was further evaluated by ex vivo experiments with a beagle dog. The experiments verified the effectiveness of the microchannel design, which will be used for the IHFD for in vivo experiments with pigs in the future.

A Precise Sampling Strip with Microstructures.

This paper presents a precise sampling microstructure formed as a paper strip. We have been developing dialysis system that can be implanted into a human body as an artificial kidney. For the safe use of our artificial kidney, the patients' urine needs to be constantly monitored to detect the abnormal value of ion concentration essential for human life. We are conceiving the monitoring system based on sampling by a paper strip. In this study, we fabricated the strip consisting of slanted and interlocked micropillars for the sampling, known as synthetic microfluidic paper. The paper-like substrate can be fabricated with a well-controlled geometry and subsequently enables precise sampling. Through the conducted experiments, it was shown that synthetic microfluidic paper had better mechanical properties, showed more precision in sampling than paper filter as well as corresponding liquid holding capability to the paper filter. Our proposed paper-based sampling system is expected to lead to the development of minimally invasive ion monitoring system with quantitative sampling strip.

Blood-Separating Device Without Energy Source for Implantable Medical Devices.

Coagulation of blood inside the implanted medical device is quite a critical problem to limit the lifetime. In this paper, we propose a microfluidic blood separating device using curved and branched channels. It utilizes centrifugal force on curved flow and separates blood flow into blood cell rich and blood cell poor ones at the bifurcation. Though it cannot separate the plasma from blood cells completely, the blood with small concentrations of blood cells will have low coagulatibity and extend the lifetime of the implant medical device. The device does not require any external pumps or valves, i.e., the system does not need any power sources but the blood pressure. We conducted experiments with a titanium foil which contacted to human whole blood with different hematocrit values for 7 days. The device was experimentally characterized with respect to the channel design. The former experiments suggested that lower concentration of blood cells helps avoiding blood coagulations, and the latter showed that the separation by our device is mainly affected by the flow rate and channel curvature.

Preparation-Free Measurement of Event-Related Potential in Oddball Tasks From Hairy Parts Using Candle-Like Dry Microneedle Electrodes.

This paper reports successful measurement of even-related potential (ERP) using candle-like dry microneedle electrodes, which can acquire high-quality electroencephalogram (EEG) from hairy parts without any pretreatment. In our previous work, we successfully measured spontaneous EEG activity and its application to assess the stress state of the subjects. ERPs originate from electrophysiological response to stimulus and are one of the most important indices to capture the cognitive and sensory activities. In this work, using the candle-like dry microelectrodes, we demonstrate successful measurement of ERPs elicited by oddball tasks. Two oddball tasks using pure tone stimuli and speech stimuli were assigned to the subjects, where EEG was acquired from the parietal region (Cz in international 10-20 system). Note that no pretreatment, such as removal of hairs and abrasion of the scalp, was applied. As a result, P300 and mismatch negativity (MMN) were successfully measured in the both oddball tasks from the averaged EEG after the stimuli. Based on these results and given the attractive natures of the candle-like dry microneedle electrodes; they do not need any skin treatment and conductive gels and they can measure EEG from the hairy parts, the developed electrodes will accelerate cognitive neuroscience research using ERPs.

Microbes Culture System Using Cellulose Tubes and Photocatalyst-Coated Glass Balls.

Currently, microbes are utilized in many fields, such as medicine, food and environment etc. For more application of microbes, we need a new culture system, which can culture target microbes in large quantities at low cost. Thereupon, we propose a culture system using cellulose tubes. Target microbes are encapsulated inside the cellulose tubes, where they acquire nutrients and oxygen through nano pores of the tubes and are protected from competitive microbes even in open environment. To further increase the amount of oxygen and nutritions available for the target microbes, we propose photocatalyst-coated glass balls (PCGB) to sterilize competing microbes outside the tubes. We experimentally verified the effectiveness of the proposed culture system by culturing Coryne gultamicum as the target microbes.

Enfold-type connecting system of artificial blood vessels for micro implantable dialysis device.

This paper reports the connecting mechanism for the artificial blood vessels along with the recent development of the micro implantable dialysis device. Our group has been studying the micro implantable dialysis device, which will drastically improve the quality of life of dialysis patients. We expect to replace the device every couple of years, which will involve surgery. In order to simplify the surgery to reduce the load to the patients, we develop a connector for the artificial vessels, which allows the exchange of the device by low invasive surgery. The connector needs to be designed not to induce blood coagulation. We designed a connecting mechanism that enfolds the artificial vessels to allow blood to contact only to the surface of the artificial vessels. In order to verify effectiveness of the proposed connecting mechanism, we investigated the connector surfaces with SEM after blood circulation tests. Then, we evaluated blood coagulation capacity of the connecting system as well as the set of the connecting system and the micro dialysis device with respect to the activated partial thromboplastin time (APTT). No remarkable increase of blood coagulation at the connecting point was observed after 72 hours of blood circulation tests. Short-term experiments for 120 minutes to evaluate APTT showed a small decrease of APTT, which needs to be further investigated in a longer-term experiments.

Development and characterization of a fully flexible stimulation system based on embedded liquid metal channels.

Neuronal stimulation systems design is highly impacted by the overall resolution and adaptability of the device to the targeted application and area to stimulate. In this study is proposed a novel design for neural micro-stimulation electrode presenting high resolution and adaptability to any targeted area via a high flexibility. The use of liquid metal micro-channels encapsulated into a polymer allowed micro-stimulation pads at the tip of the channels. It presented a high degree of patternability to match different possible applications, as well as flexibility and interesting mechanic properties to make it insertable and adaptable in soft tissues. The design, fabrication process, and study of the electrical and mechanical behavior and stability of the device are discussed. Conductive U-shaped micro-channels down to a total diameter of 110 µm could be produced.

Immediate pain relief effect of low level laser therapy for sports injuries: Randomized, double-blind placebo clinical trial.

OBJECTIVES: To determine the immediate pain relief effect of low-level laser therapy on sports injuries in athletes and degree of pain relief by the therapy. DESIGN: Double-blind, randomized, comparative clinical study. METHODS: Participants were 32 college athletes with motion pain at a defined site. Participants were randomized into two groups in which the tested or placebo laser therapy was administered to determine pain intensity from painful action before and after laser irradiation, using the Modified Numerical Rating Scale. The post-therapeutic Modified Numerical Rating Scale score was subtracted from the pre-therapeutic Modified Numerical Rating Scale score to determine pain intensity difference, and the rate of pain intensity difference to pre-therapeutic Modified Numerical Rating Scale was calculated as pain relief rate. RESULTS: Low-level laser therapy was effective in 75% of the laser group, whereas it was not effective in the placebo group, indicating a significant difference in favor of the laser group (p<0.001). Pain relief rate was significantly higher in the laser group than in the placebo group (36.94% vs. 8.20%, respectively, p<0.001), with the difference in pain relief rate being 28.74%. CONCLUSIONS: Low-level laser therapy provided an immediate pain relief effect, reducing pain by 28.74%. It was effective for pain relief in 75% of participants.

A simple method for micropatterning nanofibrous hydrogel film.

This paper propose a new fabrication process for micropatterning a nanofibrous thin film made of bacterial cellulose(BC). BC is a hydrogel produced by specific bacteria and composed of pure cellulosic nanoflbers exhibiting 3D network structure. Such nanofibrous structure is found to be appropriate for adhesion of anchorage-dependent cells. Furthermore, BC shows high biocompatibility and mechanical toughness. Thus, the microfabrication technique for BC broadens potentials for applications. In this study, we report a new method for micropatterning BC film with feature resolution comparable with photolithography technology.

Micro-tube mass production device for microbial culture.

This paper describes mass production system of micro-tubes for microbial culture in an open environment. Microbes are used in many fields, such as food, medicine, environmental and energy. We proposed a microbe culture system using hydrogel micro-tubes, which can protect the target microbes inside from competitive microbes outside of the tubes while allow oxygen and nutrition to diffuse through. The hydrogel micro-tubes can be produced by a microfluidic device, which can precisely control the flow and therefore, the tube geometry. For practical applications of the micro-tube-based microbial culture, one of the biggest challenges is the scale-up of the micro-tube-based culture system, or mass production of the tubes. We developed a fluidic system that can produce multiple micro-tubes in parallel. We characterized the mass-produced micro channels and verified the effectiveness of the system.

Evaluation of biofouling for implantable micro dialysis system.

Implantable artificial kidney can drastically improve the quality of life of the renal disease patients. In previous study, our group has developed a multi-layered micro dialysis device which is composed of micro stainless steel channels and nano-porous polyethersulfone (PES) membranes. The device conducts hemofiltration without dialysis fluids, which is advantageous in miniaturization. We investigated the water-permeability of the PES membrane through in vivo experiments using rat model of renal disease for 5 hours and verified the effectiveness of the device. We investigated the permeability of PES membrane via in vitro experiments for 24 days. Biofouling on the PES membrane was found and caused deterioration of dialysis performance of the membrane. In this research, we investigated the biofouling such as thrombus, coagulation and protein adhesion on the sidewall of the micro fluidic channels. We investigated the micro fluidic channel geometry and surface condition associated with the processing methods. Conducting in vitro experiment for 7 days, biofouling was found to be mainly caused by the surface conditions. The mirror surface formed by electrolytic etching could substantially prevent biofouling.

Electroencephalogram measurement from the hairy part of the scalp using polymer-based dry microneedle electrodes.

This paper reports a successful electroencephalogram (EEG) measurement from the hairy part of the scalp using a polymer-based dry microneedle electrode. The electrode consists of 25 pillars, each of which has a sharp microneedle on the top. Hairs are collected into the gaps of the pillars and the microneedles can reach the scalp surface. Since the microneedles can penetrate through the stratum corneum, no conductive gel is necessary to acquire high quality EEG. We experimentally investigated the pillar diameters in EEG measurement from the occipital region with hairs. The fabricated electrodes successfully measured EEG without any skin preparation or conductive gel.

Development of hydrogel microtubes for microbe culture in open environment.

This paper describes a microbe culture system in an open environment using hydrogel microtubes. In recent years, oil production microbes, such as Aurantiochytrium, have been found and are studied to produce fuels of new age instead of fossil fuels. Biomass production by microbes is promising, where scale-up, collection of the products and competition against other microbes are the most important challenges. Here, we propose to use hydrogel microtubes to encapsulate, culture, and protect microbes. The tubes can be micro- and mass-fabricated. They allow oxygen and nutrition to go through while they prevent competitive microbes from intruding inside. The microbes and byproducts can be collected together with the tubes. In this paper, we demonstrate the proof-of-concepts experiments: we fabricated hydrogel micro tubes and cultured Coryne glutamicum which produce lactic acid inside the tubes. The microbes were increased inside the tubes and protected even when competitive microbes existed in the culture media. Furthermore, we demonstrated how to collect microbes inside the tubes.

Toad's egg-like cultivation process for forming microcarriers from nanofibrous hydrogel.

This paper proposes a new method for generating microcarries from bacterial cellulose (BC). BC, which is produced by specific bacteria, is a hydrogel composed of a three dimensional network structure formed by cellulose nanofibers. BC as an ECM-like nanofibrous material exhibits an excellent environment for cellular adhesion. Moreover, BC has a high biocompatibility and mechanical strength. From these properties, BC is expected to be applied for microcarriers, which is used for cultivating anchorage-dependent cells. Then, we developed a microfabrication process to create BC microcarriers by using gelatin microspheres as sacrificial architectures. In addition, the monodispersity of the formed BC microcarreirs was investigated.

Development of implantable hemodialysis system using PES membranes with high water-permeability.

This paper presents development of high water-permeable dialysis membranes. We proposed the system that does not use dialysis fluid for the implantable micro dialysis treatment and development of such membranes is crucial. We developed micro dialysis system composed by nanoporous membranes and microfluidic channels in our prior work. The membranes were made of nanoporous polyethersulfone (PES), which was not water-permeable. By not using dialysate, our device can be simplified because the pumps and storage tanks for the dialysis fluid are not necessary. This treatment is termed as hemofiltration. We measured the water permeability of PES membrane with respect to the concentrations of the PES, the additives, and the solvents in the casting solution. We could find the membranes with sufficiently high water permeability through in vitro experiments using a syringe pomp and whole cow blood, and the membrane had enough mechanical strength. We conducted experiments with multi-layered device in in vitro and in vivo using rats, where the system was connected to the vein and artery. We successfully collected the filtrate beyond target line, which was set by a medical doctor, without any leakage of blood from the device. The results verified that the filtration device can be scaled-up by increasing a number of the layer. We connected the device to a rat for 5h. It was verified the device maintained almost constant water permeability beyond our target line.

The 1-year decline in estimated glomerular filtration rate (eGFR) after radical nephrectomy in patients with renal masses and matched living kidney donors is the same.

OBJECTIVES: To determine short-term differences in renal function evolution between patients with renal cell carcinoma (RCC) submitted to radical nephrectomy (RN) and living kidney donors matched for age and gender. To assess the role of co-morbidity as a risk factor for developing an estimated glomerular filtration rate (eGFR) of <60 mL/min/1.73 m(2) . PATIENTS AND METHODS: In this retrospective study patients undergoing Radical Nefrectomy (RN) between January 2000 and February 2011 for suspicion of localised RCC were matched by age and gender to living kidney donors. Renal function was compared between the groups using the Modification in Diet and Renal Disease (MDRD) equation at 1 year after RN. Charlson co-morbidity score, incidence of hypertension, diabetes and cardiovascular disease were compared and assessed as predictors for developing an eGFR of <60 mL/min/1.73 m(2) . RESULTS: In all, 196 patients were included, 98 in each group. The mean age was respectively 60.6 (RCC group) and 59.1 years (donors). The 1-year postoperative mean eGFR (available in 89 patients with RCC and 87 donors) was similar, at a mean (sd) of 56.7 (16.4) mL/min/1.73 m(2) in patients with RCC and 56.2 (9.8) mL/min/1.73 m(2) in donors (P = 0.83). In patients with RCC the incidence and severity of co-morbidities was significantly higher. A preoperative eGFR of 60-89 mL/min/1.73 m(2) was the only independent risk factor for developing a postoperative eGFR of <60 mL/min/1.73 m(2) (odds ratio 4.4, confidence interval 2.1-9.5, P < 0.001, 95% confidence interval). CONCLUSIONS: In our cohorts with advanced age the 1-year follow-up eGFR was similar in both groups. Despite increased co-morbidity in the RCC group there was no increased decline in renal function. Only reduced preoperative eGFR could be identified as risk factor for developing a postoperative eGFR of <60 mL/min/1.73 m(2) .

Prognostic models and factors for patients with renal-cell carcinoma: a survey on their use among urologists.

PURPOSE: To assess the use of prognostic factors and models in renal-cell carcinoma (RCC) and to gain insight in the motivations precluding prognosis estimation and the use of prognosticators. MATERIALS AND METHODS: A questionnaire was sent to 110 urologists involved in the Clinical Research Office of the Endourological Society (CROES) Global Renal Mass Study. Frequencies were gathered using descriptive statistics. RESULTS: The majority of the 86 responders worked in a university hospital in Europe. Most of the urologists (97.7%) used the tumor-node-metastasis (TNM) classification, and 44% performed prognosis estimations in all patients. The main reason not to estimate prognosis was lack of accuracy (20.9%) and of additional benefit (11.6%). In addition, clinical, laboratory, or pathologic factors were used by 89.5% of the urologists and biomarkers by 16.3%. Preoperative models were used by 20.9%, postoperative models by 38.4%, and metastatic models by 38.4%. The Raj and Motzer models were the most used in preoperative and metastatic settings, while no predominance among the different postoperative models was seen. The most important reasons to skip the use of models were "lack of additional value" and "lack of familiarity" reported by 30.2% and 27.9% of the responders, respectively. CONCLUSIONS: The TNM is the mainstay for assessing prognosis in RCC. Our data indicate that penetration of prognostic systems is, at most, moderate, suggesting limited use outside original developmental settings. On the contrary, clinical, laboratory, and pathologic factors are used by almost all urologists for prognosis estimations. The most important reason not to use models is the lack of additional value.

Age and gender related differences in renal cell carcinoma in a European cohort.

PURPOSE: We evaluated the influence of age on gender related differences in the renal cell carcinoma presentation of patients operated on between 1995 and 2005 in a European country. We also assessed the trend of missing pathological data. MATERIALS AND METHODS: Data on all patients who underwent radical or partial nephrectomy for renal cell carcinoma during 1995 to 2005 in The Netherlands were retrospectively collected from the prospective PALGA (Pathological Anatomical National Automated Archive) database. Patients were divided into 5 cohorts based on age at surgery, including 40 or less, 41 to 50, 51 to 60, 61 to 70 and greater than 70 years. Variables evaluated were gender differences by age, and tumor size, subtype, stage and Fuhrman grade. RESULTS: A higher mean age in women was only observed in those older than 70 years (p <0.001). The male-to-female ratio was 2:1 at ages 41 to 60 years and 1.2:1 at greater than 70 years. Compared to men women had smaller tumors at ages 51 to 60 years (p = 0.03), stage pT3 was less common at age 41 years or greater (p = 0.02), and grade 2 was less common at age 61 years or greater (p <0.001). The incidence of tumors with missing data on stage (14.9%), subtype (52.2%) and grade (47.1%) decreased substantially during the study period (p <0.001). CONCLUSIONS: Older age in women than in men who present to surgery for RCC was only prevalent in those older than 70 years. The male-to-female ratio was almost equal in patients older than 70 years compared to a 2:1 ratio at ages 41 to 60 years. Women presented with fewer pT3 tumors than men at age 41 years or greater. Missing pathological data decreased significantly between 1995 and 2005.

Are there parameters that predict a nondiagnostic biopsy outcome taken during laparoscopic-assisted cryoablation of small renal tumors?

BACKGROUND AND PURPOSE: The histopathologic diagnosis of a small renal mass (SRM) that is managed with cryoablation relies on preoperative or intraoperative biopsies. Because a considerable number of these SRMs are benign, accurate diagnosis has prognostic and follow-up implications. The main problem in SRMs is the high rate of nondiagnostic biopsies. Our purpose was to assess whether certain tumor and biopsy characteristics are correlated with a diagnostic biopsy outcome. PATIENTS AND METHODS: One hundred tumors that were smaller than 4.5 cm in 94 patients were managed with laparoscopic cryoablation. After dissection of the perirenal fat and identification of the tumor by intra-abdominal ultrasonography, one or more biopsies were obtained before freezing. Using the Student t/Mann Whitney U test, the following parameters were evaluated for predicting biopsy outcome: Tumor size, location, and exophytic part of the tumor, size of the biopsy needle, the number of biopsies taken, and presence of nonenhancing areas compatible with necrosis inside the tumors. Correlations among parameters were assessed using a Spearman correlation or Kruskal-Wallis test. RESULTS: Twenty-two (22%) biopsies were nondiagnostic and consisted of normal kidney tissue, connective tissue, fat, fibrosis, necrosis, and/or blood. There were no significant differences in parameters between the diagnostic and nondiagnostic group. There was a positive correlation between tumor size and number of biopsies (P=0.029) and between the presence of nonenhancing areas and both size (P<0.001) and the number of biopsies taken (P<0.001). CONCLUSION: No statistical significant correlation was found between biopsy outcome and tumor or biopsy characteristics. More biopsies were taken in larger tumors, and larger tumors contained more nonenhancing areas that were suspect for necrosis.