Background
With improved short-term surgical outcomes, laparoscopic distal gastrectomy has rapidly gained popularity. However, the safety and feasibility of laparoscopic total gastrectomy (LTG) has ...not yet been proven due to the difficulty of the technique. This single-arm prospective multi-center study was conducted to evaluate the use of LTG for clinical stage I gastric cancer.
Methods
Between October 2012 and January 2014, 170 patients with pathologically proven, clinical stage I gastric adenocarcinoma located at the proximal stomach were enrolled. Twenty-two experienced surgeons from 19 institutions participated in this clinical trial. The primary end point was the incidence of postoperative morbidity and mortality at postoperative 30 days. The severity of postoperative complications was categorized according to Clavien–Dindo classification, and the incidence of postoperative morbidity and mortality was compared with that in a historical control.
Results
Of the enrolled patients, 160 met criteria for inclusion in the full analysis set. Postoperative morbidity and mortality rates reached 20.6% (33/160) and 0.6% (1/160), respectively. Fifteen patients (9.4%) had grade III or higher complications, and three reoperations (1.9%) were performed. The incidence of morbidity after LTG in this trial did not significantly differ from that reported in a previous study for open total gastrectomy (18%).
Conclusions
LTG performed by experienced surgeons showed acceptable postoperative morbidity and mortality for patients with clinical stage I gastric cancer.
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Although stiffness-controllable substrates have been developed to investigate the effect of stiffness on cell behavior and function, the use of separate substrates with different ...degrees of stiffness, substrates with a narrow range stiffness gradient, toxicity of residues, different surface composition, complex fabrication procedures/devices, and low cell adhesion are still considered as hurdles of conventional techniques. In this study, a cylindrical polyvinyl alcohol (PVA)/hyaluronic acid (HA) hydrogel with a wide-range stiffness gradient (between ∼20kPa and ∼200kPa) and cell adhesiveness was prepared by a liquid nitrogen (LN2)-contacting gradual freezing–thawing method that does not use any additives or specific devices to produce the stiffness gradient hydrogel. From an in vitro cell culture using the stiffness gradient PVA/HA hydrogel, it was observed that human bone marrow mesenchymal stem cells have favorable stiffness ranges for induction of differentiation into specific cell types (∼20kPa for nerve cell, ∼40kPa for muscle cell, ∼80kPa for chondrocyte, and ∼190kPa for osteoblast). The PVA/HA hydrogel with a wide range of stiffness spectrum can be a useful tool for basic studies related with the stem cell differentiation, cell reprogramming, cell migration, and tissue regeneration in terms of substrate stiffness.
It is postulated that the stiffness of the extracellular matrix influences cell behavior. To prove this concept, various techniques to prepare substrates with a stiffness gradient have been developed. However, the narrow ranges of stiffness gradient and complex fabrication procedures/devices are still remained as limitations. Herein, we develop a substrate (hydrogel) with a wide-range stiffness gradient using a gradual freezing–thawing method which does not need specific devices to produce a stiffness gradient hydrogel. From cell culture experiments using the hydrogel, it is observed that human bone marrow mesenchymal stem cells have favorable stiffness ranges for induction of differentiation into specific cell types (∼20kPa for nerve, ∼40kPa for muscle, ∼80kPa for cartilage, and ∼190kPa for bone in our hydrogel system).
Current guidelines recommend dual antiplatelet therapy (DAPT) of aspirin plus a P2Y12 inhibitor for at least 12 months after implantation of drug-eluting stents (DES) in patients with acute coronary ...syndrome. However, available data about the optimal duration of DAPT in patients with acute coronary syndrome undergoing percutaneous coronary intervention are scant. We aimed to investigate whether a 6-month duration of DAPT would be non-inferior to the conventional 12-month or longer duration of DAPT in this population.
We did a randomised, open-label, non-inferiority trial at 31 centres in South Korea. Patients were eligible if they had unstable angina, non-ST-segment elevation myocardial infarction, or ST-segment elevation myocardial infarction, and underwent percutaneous coronary intervention. Enrolled patients were randomly assigned, via a web-based system by computer-generated block randomisation, to either the 6-month DAPT group or to the 12-month or longer DAPT group, with stratification by site, clinical presentation, and diabetes. Assessors were masked to treatment allocation. The primary endpoint was a composite of all-cause death, myocardial infarction, or stroke at 18 months after the index procedure in the intention-to-treat population. Secondary endpoints were the individual components of the primary endpoint; definite or probable stent thrombosis as defined by the Academic Research Consortium; and Bleeding Academic Research Consortium (BARC) type 2–5 bleeding at 18 months after the index procedure. The primary endpoint was also analysed per protocol. This trial is registered with ClinicalTrials.gov, number NCT01701453.
Between Sept 5, 2012, and Dec 31, 2015, we randomly assigned 2712 patients; 1357 to the 6-month DAPT group and 1355 to the 12-month or longer DAPT group. Clopidogrel was used as a P2Y12 inhibitor for DAPT in 1082 (79·7%) patients in the 6-month DAPT group and in 1109 (81·8%) patients in the 12-month or longer DAPT group. The primary endpoint occurred in 63 patients in the 6-month DAPT group and in 56 patients in the 12-month or longer DAPT group (cumulative event rate 4·7% vs 4·2%; absolute risk difference 0·5%; upper limit of one-sided 95% CI 1·8%; pnon-inferiority=0·03 with a predefined non-inferiority margin of 2·0%). Although all-cause mortality did not differ significantly between the 6-month DAPT group and the 12-month or longer DAPT group (35 2·6% patients vs 39 2·9%; hazard ratio HR 0·90 95% CI 0·57–1·42; p=0·90) and neither did stroke (11 0·8% patients vs 12 0·9%; 0·92 0·41–2·08; p=0·84), myocardial infarction occurred more frequently in the 6-month DAPT group than in the 12-month or longer DAPT group (24 1·8% patients vs ten 0·8%; 2·41 1·15–5·05; p=0·02). 15 (1·1%) patients had stent thrombosis in the 6-month DAPT group compared with ten (0·7%) in the 12-month or longer DAPT group (HR 1·50 95% CI 0·68–3·35; p=0·32). The rate of BARC type 2–5 bleeding was 2·7% (35 patients) in the 6-month DAPT group and 3·9% (51 patients) in the 12-month or longer DAPT group (HR 0·69 95% CI 0·45–1·05; p=0·09). Results from the per-protocol analysis were similar to those from the intention-to-treat analysis.
The increased risk of myocardial infarction with 6-month DAPT and the wide non-inferiority margin prevent us from concluding that short-term DAPT is safe in patients with acute coronary syndrome undergoing percutaneous coronary intervention with current-generation DES. Prolonged DAPT in patients with acute coronary syndrome without excessive risk of bleeding should remain the standard of care.
Abbott Vascular Korea, Medtronic Vascular Korea, Biosensors Inc, and Dong-A ST.
The use of plant biomass for biofuel production will require efficient utilization of the sugars in lignocellulose, primarily glucose and xylose. However, strains of Saccharomyces cerevisiae ...presently used in bioethanol production ferment glucose but not xylose. Yeasts engineered to ferment xylose do so slowly, and cannot utilize xylose until glucose is completely consumed. To overcome these bottlenecks, we engineered yeasts to coferment mixtures of xylose and cellobiose. In these yeast strains, hydrolysis of cellobiose takes place inside yeast cells through the action of an intracellular β-glucosidase following import by a high-affinity cellodextrin transporter. Intracellular hydrolysis of cellobiose minimizes glucose repression of xylose fermentation allowing coconsumption of cellobiose and xylose. The resulting yeast strains, cofermented cellobiose and xylose simultaneously and exhibited improved ethanol yield when compared to fermentation with either cellobiose or xylose as sole carbon sources. We also observed improved yields and productivities from cofermentation experiments performed with simulated cellulosic hydrolyzates, suggesting this is a promising cofermentation strategy for cellulosic biofuel production. The successful integration of cellobiose and xylose fermentation pathways in yeast is a critical step towards enabling economic biofuel production.
Biportal endoscopic spinal surgery (BESS) is a minimally invasive spinal surgery, which is basically similar to microscopic spinal surgery in terms of the use of floating technique and technically ...similar to conventional percutaneous endoscopic spinal surgery in terms of the use of endoscopic or arthroscopic instruments. Using two independent portals (viewing and working) and maintaining a certain distance from the bony and neural structures allow closer access to the target lesion through a panoramic view by free handling of the scope and instruments rather than through a fixed view by docking into the Kambin's triangle. Minimally invasive surgery allows for reduced dissection and inevitable muscle injury, preserving stability and reducing risks of restabilization. The purpose of fusion surgery is the same as that of the three surgical techniques stated above. Its wider range of view helps to overcome limitations of conventional endoscopic spinal surgery and to supplement the weak points of microscopic spinal surgery, such as limited working space in a tubular retractor and difficulty in accessing the contralateral area. This technique provides an alternative to unilateral or bilateral decompression of lumbar central spinal stenosis, foraminal stenosis, low-grade spondylolisthesis, and adjacent segment degeneration. Early clinical outcomes are promising despite potential for complications, such as dural tearing and postoperative epidural hematoma, similar to other procedures. Merits of BESS include decreased postoperative infection rate due to continuous irrigation throughout the procedure and decreased need for fusion surgery for one- or two-level lumbar stenosis by wide sublaminar and foraminal decompression with minimal sacrifice of stabilizing structures.
Human sweat contains vast physiological information, which has been a promising resource for on‐body and real‐time health monitoring. Wearable sweat sensors have recently attracted an ever‐increasing ...interest due to their promising capabilities for continuously tracking changes in health status. However, the commercialization of sweat sensors is seriously hindered by drawbacks of materials including high manufacturing and consumables costs, complex integration technology, as well as limited electrochemical signal transduction. In this review, sweat sensing principles are elaborately interpreted, and the latest advances in functional materials for biomarkers sensing in sweat are systematically summarized. Subsequently, the complex structure–activity relationships between various functional materials and sensing capabilities are further elucidated by coupling chemical structures, geometrics, electrochemical properties, and approaches for materials manufacturing. Furthermore, the integration of each component into sensing device for sweat detection and analysis is also discussed. Finally, challenges and opportunities for wearable sweat sensors are delineated in the development of future personalized and predictive healthcare.
Wearable electrochemical sweat sensors have emerged as a type of promising electronic device for continuous monitoring human health. This article reviews the recent progress on various materials for electrochemical sweat sensing. Structure‐activity relationships of sensing materials, approaches for materials manufacturing, and integration of devices are discussed. Challenges and future research directions are also identified.
We evaluated changes in incidence, relative survival (RS), and conditional survival (CS) of head and neck squamous cell carcinoma (HNSCC), focusing on oral tongue squamous cell carcinoma (OTSCC). ...Data of 74 680 HNSCC patients from 1976 to 2015 were obtained from the Surveillance, Epidemiology, and End Results database. Five anatomical sites and their subsites were analyzed. Annual percent change (APC) of incidence was calculated. RS and CS were compared across the four decades. Adjusted hazard ratios (aHRs) of RS were evaluated using multivariate regression. OTSCC incidence decreased from 1976 (APC = -0.76, P < 0.05) but has increased since 1999 (APC = 2.36, P < 0.05). During 2006-2015, the 5-year CS exceeded 90% only for OTSCC and oropharyngeal squamous cell carcinoma (OPSCC). RS improved in OTSCC (aHR = 0.697, 95% confidence interval CI 0.642-0.757, P < 0.001) and OPSCC (aHR = 0.669, 95% CI 0.633-0.706, P < 0.001) during the last two decades. For both OTSCC and OPSCC, improved survival was observed regardless of treatment. Incidence and survival remained unchanged for nasopharyngeal, hypopharyngeal, and laryngeal cancers during this period. In conclusion, OTSCC incidence has been increasing since the 2000s, with improving prognosis irrespective of treatment. Given its similarity to OPSCC, OTSCC may represent an emerging HNSCC, warranting further research and clinical recognition.
•IRB/AML fixed-dose regimens show superior antihypertensive efficacy over IRB monotherapy.•A potential benefit of IRB/AML regimens was noted in the elderly and T2DM patients.•IRB/AML combinations are ...well-tolerated and have comparable safety to IRB monotherapy.
This study aimed to evaluate the efficacy and tolerability of irbesartan (IRB) and amlodipine (AML) combination therapy in patients with essential hypertension whose blood pressure (BP) was not controlled by IRB monotherapy.
Two multicenter, randomized, double-blind, placebo-controlled, phase III studies were conducted in Korea (the I-DUO 301 study and the I-DUO 302 study). After a 4-week run-in period with either 150 mg IRB (I-DUO 301 study) or 300 mg IRB (I-DUO 302 study), patients with uncontrolled BP (ie, mean sitting systolic BP MSSBP ≥140 mmHg to <180 mmHg and mean sitting diastolic BP <110 mmHg) were randomized to the placebo, AML 5 mg, or AML 10 mg group. A total of 428 participants were enrolled in the 2 I-DUO studies. In the I-DUO 301 study, 271 participants were randomized in a 1:1:1 ratio to receive either IRB/AML 150/5 mg, IRB/AML 150/10 mg, or IRB 150 mg/placebo. In the I-DUO 302 study, 157 participants were randomized in a 1:1 ratio to receive IRB/AML 300/5 mg or IRB 300 mg/placebo. The primary endpoint was the change in MSSBP from baseline to week 8. Tolerability was assessed according to the development of treatment-emergent adverse events (TEAEs) and clinically significant changes in physical examination, laboratory tests, pulse, and 12-lead electrocardiography.
In I-DUO 301, the mean (SD) changes of MSSBP at week 8 from baseline were −14.78 (12.35) mmHg, −21.47 (12.78) mmHg, and −8.61 (12.19) mmHg in the IRB/AML 150/5 mg, IRB/AML 150/10 mg, and IRB 150 mg/placebo groups, respectively. In I-DUO 302, the mean (SD) changes of MSSBP at week 8 from baseline were −13.30 (12.47) mmHg and −7.19 (15.37) mmHg in the IRB/AML 300/5 mg and IRB 300 mg/placebo groups, respectively. In both studies, all combination groups showed a significantly higher reduction in MSSBP than the IRB monotherapy groups (P < 0.001 for both). TEAEs occurred in 10.00%, 10.99%, and 12.22% of participants in the IRB/AML 150/5 mg, IRB/AML 150/10 mg, and IRB 150 mg/placebo groups, respectively, in I-DUO 301 and in 6.33% and 10.67% of participants in the IRB/AML 300/5 mg and IRB 300 mg/placebo groups, respectively, in I-DUO 302, with no significant between-group differences. Overall, there was one serious adverse event throughout I-DUO study.
The combination of IRB and AML has superior antihypertensive effects compared with IRB alone over an 8-week treatment period, with placebo-like tolerability.
ClinicalTrials.gov identifier: NCT05476354 (I-DUO 301), NCT05475665 (I-DUO 302).
Ionogels are good candidates for flexible electronics owing to their excellent mechanical and electrical properties, including stretchability, high conductivity, and stability. In this study, ...conducting ionogels comprising a double network (DN) of poly(N‐isopropylacrylamide‐co‐N,N′‐diethylacrylamide)/chitosan which are further reinforced by the ionic and covalent crosslinking of the chitosan network by tripolyphosphate and glutaraldehyde, respectively, are prepared. Based on their excellent mechanical properties and high conductivity, the developed DN ionogels are envisioned as stretchable ionic conductors for extremely stretchable alternating‐current electroluminescent (ACEL) devices. The ACEL device fabricated with the developed ionogel exhibits stable working operation under an ultrahigh elongation of over 1200% as well as severe mechanical deformations such as bending, rolling, and twisting. Furthermore, the developed ACEL devices also display stable luminescence over 1000 stretch/release cycles or at temperatures as harsh as 200 °C.
A super stretchable electroluminescent device is successfully fabricated with double‐network ionogel as a soft electrode owing to its excellent mechanical robustness and electrical conductivity. The fabricated device exhibits extremely stable light‐emitting operation even at high elongation as well as demonstrating mechanical, electrical, and thermal stability, which can be applied to new types of stretchable light display and sensors.
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