Background
Sentinel node navigation surgery reduces the extent of gastric and lymph node dissection, and may improve quality of life. The benefit and harm of laparoscopic sentinel node navigation ...surgery (LSNNS) for early gastric cancer is unknown. The SENORITA (SEntinel Node ORIented Tailored Approach) trial investigated the pathological and surgical outcomes of LSNNS compared with laparoscopic standard gastrectomy (LSG) with lymph node dissection.
Methods
The SENORITA trial was an investigator‐initiated, open‐label, parallel‐assigned, non‐inferiority, multicentre RCT conducted in Korea. The primary endpoint was 3‐year disease‐free survival. The secondary endpoints, morbidity and mortality within 30 days of surgery, are reported in the present study.
Results
A total of 580 patients were randomized to LSG (292) or LSNNS (288). Surgery was undertaken in 527 patients (LSG 269, LSNNS 258). LSNNS could be performed according to the protocol in 245 of 258 patients, and a sentinel node basin was detected in 237 (96·7 per cent) Stomach‐preserving surgery was carried out in 210 of 258 patients (81·4 per cent). Postoperative complications occurred in 51 patients in the LSG group (19·0 per cent) and 40 (15·5 per cent) in the LSNNS group (P = 0·294). Complications with a Clavien–Dindo grade of III or higher occurred in 16 (5·9 per cent) and 13 (5·0 per cent) patients in the LSG and LSNNS groups respectively (P = 0·647).
Conclusion
The rate and severity of complications following LSNNS for early gastric cancer are comparable to those after LSG with lymph node dissection. Registration number: NCT01804998 (
http://www.clinicaltrials.gov).
Antecedentes
La cirugía de navegación del ganglio centinela (sentinel node navigation surgery, SNNS) reduce la extensión de la resección gástrica y ganglionar, y puede mejorar la calidad de vida. Se desconoce el beneficio y el daño de la cirugía de navegación del ganglio centinela por vía laparoscópica (laparoscopic sentinel node navigation surgery, LSNNS) para el cáncer gástrico precoz. El ensayo clínico SENORITA investigó los resultados patológicos y quirúrgicos de LSNNS en comparación con la gastrectomía laparoscópica estándar (laparoscopic gastrectomy, LSG) con disección ganglionar (lymph node dissection, LND).
Métodos
El ensayo SENORITA fue un ensayo multicéntrico aleatorizado y controlado, iniciado por investigadores, abierto, con asignación a grupos paralelos y de no inferioridad llevado a cabo en Corea. El resultado primario fue la supervivencia libre de enfermedad a los 3 años. En el presente estudio, se describen los resultados secundarios correspondientes a morbilidad y mortalidad a los 30 días del postoperatorio.
Resultados
Un total de 580 pacientes fueron aleatorizados a LG (n = 292) o LSNNS (n = 288). La cirugía se realizó en 527 pacientes (LG 269, LSNNS 258). LSNNS pudo ser realizada de acuerdo con el protocolo en 245 de 258 pacientes y en 237 de 245 pacientes (96,7%) se detectó un ganglio centinela. La cirugía con preservación del estómago se realizó en 210 de 258 pacientes (81,4%). Las complicaciones postoperatorias se presentaron en 51 pacientes del grupo LSG (19,0%) y en 40 pacientes (15,5%) del grupo LSNNS (P = 0,294). Las complicaciones grado III o mayor de Clavien‐Dindo se detectaron en 16 (5,9%) y 13 pacientes (5,0%) de los grupos LSG y LSNNS, respectivamente (P = 0,647).
Conclusión
El porcentaje y la gravedad de las complicaciones tras LSNNS para cancer gástrico precoz son comparables a la LSG con LND.
The prospective, multicentre, randomized controlled phase III SENORITA trial evaluated the surgical and oncological outcomes of laparoscopic sentinel node navigation surgery (LSNNS) compared with laparoscopic standard gastrectomy (LSG) with lymph node dissection (LND) for early gastric cancer (EGC). LSNNS for EGC is a safe procedure in terms of postoperative morbidity and mortality compared with LSG and LND. ESD, endoscopic submucosal dissection; mITT, modified intention to treat; FAS, full analysis set; OGJ, oesophagogastric junction; LDG, laparoscopic distal gastrectomy; LTG, laparoscopic total gastrectomy; LPPG, laparoscopic pylorus‐preserving gastrectomy; LPG, laparoscopic proximal gastrectomy; ODG, open distal gastrectomy; OTG, open total gastrectomy; PP, per protocol; SBD, sentinel basin dissection; EFTR, endoscopic full‐thickness resection; LWR, laparoscopic wedge resection; LSR, laparoscopic segmental resection.
Similar morbidity
Thin-film field-effect transistors are essential elements of stretchable electronic devices for wearable electronics. All of the materials and components of such transistors need to be stretchable ...and mechanically robust. Although there has been recent progress towards stretchable conductors, the realization of stretchable semiconductors has focused mainly on strain-accommodating engineering of materials, or blending of nanofibres or nanowires into elastomers. An alternative approach relies on using semiconductors that are intrinsically stretchable, so that they can be fabricated using standard processing methods. Molecular stretchability can be enhanced when conjugated polymers, containing modified side-chains and segmented backbones, are infused with more flexible molecular building blocks. Here we present a design concept for stretchable semiconducting polymers, which involves introducing chemical moieties to promote dynamic non-covalent crosslinking of the conjugated polymers. These non-covalent crosslinking moieties are able to undergo an energy dissipation mechanism through breakage of bonds when strain is applied, while retaining high charge transport abilities. As a result, our polymer is able to recover its high field-effect mobility performance (more than 1 square centimetre per volt per second) even after a hundred cycles at 100 per cent applied strain. Organic thin-film field-effect transistors fabricated from these materials exhibited mobility as high as 1.3 square centimetres per volt per second and a high on/off current ratio exceeding a million. The field-effect mobility remained as high as 1.12 square centimetres per volt per second at 100 per cent strain along the direction perpendicular to the strain. The field-effect mobility of damaged devices can be almost fully recovered after a solvent and thermal healing treatment. Finally, we successfully fabricated a skin-inspired stretchable organic transistor operating under deformations that might be expected in a wearable device.
Background and purpose
The rate at which the chance of a good outcome of endovascular stroke therapy (EVT) decays with time when eligible patients are selected by baseline diffusion‐weighted magnetic ...resonance imaging (DWI‐MRI) and whether ischaemic core size affects this rate remain to be investigated.
Methods
This study analyses a prospective multicentre registry of stroke patients treated with EVT based on pretreatment DWI‐MRI that was categorized into three groups: small Diffusion‐Weighted Imaging Alberta Stroke Program Early Computed Tomography Score (DWI‐ASPECTS) (8–10), moderate (5–7) and large (<5) cores. The main outcome was a good outcome at 90 days (modified Rankin Scale 0–2). The interaction between onset‐to‐groin puncture time (OTP) and DWI‐ASPECTS categories regarding functional outcomes was investigated.
Results
Ultimately, 985 patients (age 69 ± 11 years; male 55%) were analysed. Potential interaction effects between the DWI‐ASPECTS categories and OTP on a good outcome at 90 days were observed (Pinteraction = 0.06). Every 60‐min delay in OTP was associated with a 16% reduced likelihood of a good outcome at 90 days amongst patients with large cores, although no associations were observed amongst patients with small to moderate cores. Interestingly, the adjusted rates of a good outcome at 90 days steeply declined between 65 and 213 min of OTP and then remained smooth throughout 24 h of OTP (Pnonlinearity = 0.15).
Conclusions
Our study showed that the probability of a good outcome after EVT nonlinearly decreased, with a steeper decline at earlier OTP than at later OTP. Discrepant effects of OTP on functional outcomes by baseline DWI‐ASPECTS categories were observed. Thus, different strategies for EVT based on time and ischaemic core size are warranted.
International Consensus on drug allergy Demoly, P.; Adkinson, N. F.; Brockow, K. ...
Allergy,
April 2014, Volume:
69, Issue:
4
Journal Article, Conference Proceeding
Peer reviewed
Open access
When drug reactions resembling allergy occur, they are called drug hypersensitivity reactions (DHRs) before showing the evidence of either drug‐specific antibodies or T cells. DHRs may be allergic or ...nonallergic in nature, with drug allergies being immunologically mediated DHRs. These reactions are typically unpredictable. They can be life‐threatening, may require or prolong hospitalization, and may necessitate changes in subsequent therapy. Both underdiagnosis (due to under‐reporting) and overdiagnosis (due to an overuse of the term ‘allergy’) are common. A definitive diagnosis of such reactions is required in order to institute adequate treatment options and proper preventive measures. Misclassification based solely on the DHR history without further testing may affect treatment options, result in adverse consequences, and lead to the use of more‐expensive or less‐effective drugs, in contrast to patients who had undergone a complete drug allergy workup. Several guidelines and/or consensus documents on general or specific drug class‐induced DHRs are available to support the medical decision process. The use of standardized systematic approaches for the diagnosis and management of DHRs carries the potential to improve outcomes and should thus be disseminated and implemented. Consequently, the International Collaboration in Asthma, Allergy and Immunology (iCAALL), formed by the European Academy of Allergy and Clinical Immunology (EAACI), the American Academy of Allergy, Asthma and Immunology (AAAAI), the American College of Allergy, Asthma and Immunology (ACAAI), and the World Allergy Organization (WAO), has decided to issue an International CONsensus (ICON) on drug allergy. The purpose of this document is to highlight the key messages that are common to many of the existing guidelines, while critically reviewing and commenting on any differences and deficiencies of evidence, thus providing a comprehensive reference document for the diagnosis and management of DHRs.
Summary Adult articular chondrocytes undergo slow senescence and dedifferentiation during in vitro expansion, restricting successful cartilage regeneration. A complete understanding of the molecular ...signaling pathways involved in the senescence and dedifferentiation of chondrocytes is essential in order to better characterize chondrocytes for cartilage tissue engineering applications. During expansion, cell fate is determined by the change in expression of various genes in response to aspects of the microenvironment, including oxidative stress, mechanical stress, and unsuitable culture conditions. Rapid senescence or dedifferentiation not only results in the loss of the chondrocytic phenotype but also enhances production of inflammatory mediators and matrix-degrading enzymes. This review focuses on the two groups of genes that play direct and indirect roles in the induction of senescence and dedifferentiation. Numerous degenerative signaling pathways associated with these genes have been reported. Upregulation of the genes interleukin 1 beta ( IL-1β ), p53 , p16 , p21 , and p38 mitogen-activated protein kinase ( MAPK ) is responsible for the direct induction of senescence, whereas downregulation of the genes transforming growth factor-beta ( TGF-β ), bone morphogenetic protein-2 ( BMP-2 ), SRY (sex determining region Y)-box 9 ( SOX9 ), and insulin-like growth factor-1 ( IGF-1 ), indirectly induces senescence. In senescent and dedifferentiated chondrocytes, it was found that TGF - β , BMP - 2 , SOX9 , and IGF-1 are downregulated, while the levels of IL - 1β , p53 , p16 , p21 , and p38 MAPK are upregulated followed by inhibition of the normal molecular functioning of the chondrocytes. This review helps to elucidate the underlying mechanism in degenerative cartilage disease, which may help to improve cartilage tissue regeneration techniques.
Background and purpose
High blood pressure (BP) at presentation is associated with poor outcomes in acute ischaemic stroke, but serial BP measurements may better delineate the clinical implications ...of BP. The aim was to investigate the association between various BP parameters and functional outcomes in acute ischaemic stroke patients treated with endovascular thrombectomy (EVT).
Methods
This study reports a retrospective analysis of a prospective registry of a comprehensive stroke centre. Patients treated with EVT due to large vessel occlusion in the anterior circulation were enrolled. BP was measured hourly during the first 24 h after admission. Associations of various BP parameters, including BP variability, with functional outcomes at 3 months, including good outcomes (modified Rankin Scale score of 0–2), were analysed.
Results
Of the 378 enrolled patients (mean age 70 ± 11 years, male 54.2%), 313 (82.8%) achieved successful reperfusion after EVT, and 149 (39.4%) had good outcomes at 3 months. Higher mean systolic BP each 10 mmHg increase, odds ratio 0.82 (0.69–0.97) and higher systolic successive variation (SV) each 10% increase, odds ratio 0.37 (0.18–0.76) were associated with a reduced likelihood of achieving good outcomes. In addition, reperfusion status after EVT moderated the influence of higher systolic SV on good outcomes (Pint = 0.05).
Conclusion
The results showed that a higher mean systolic BP and systolic SV during the first 24 h of EVT reduced the likelihood of good outcomes at 3 months. The effects of these parameters on outcomes are more substantial amongst patients with successful reperfusion after EVT, suggesting that different BP control strategies should be employed according to reperfusion status.
Click here to view the accompanying paper in this volume.
Kuroshio velocity structure and transport in the East China Sea (ECS) were investigated as part of a 23‐month study using inverted echo sounders and acoustic Doppler current profilers (ADCPs) along ...the regularly sampled PN‐line. Flow toward the northeast is concentrated near the continental shelf with the mean surface velocity maximum located 30 km offshore from the shelf break (taken as the 170 m isobath). There are two regions of southwestward flow: a deep countercurrent over the continental slope beneath the Kuroshio axis and a recirculation offshore which extends throughout the whole water column. There is a bimodal distribution to the depth of maximum velocity with occurrence peaks at the surface and 210 dbar. When the maximum velocity is located within the top 80 m of the water column, it ranges between 0.36 m/s and 2.02 m/s; when the maximum velocity is deeper than 80 m, it ranges between 0.31 m/s and 1.11 m/s. The 13‐month mean net absolute transport of the Kuroshio in the ECS is 18.5 ± 0.8 Sv (standard deviation, σ = 4.0 Sv). The mean positive and negative portions of this net flow are 24.0 ± 0.9 Sv and −5.4 ± 0.3 Sv, respectively.
ABSTRACT We report on the results of a recent blind search survey for gamma-ray pulsars in Fermi Large Area Telescope (LAT) data being carried out on the distributed volunteer computing system, ...Einstein@Home. The survey has searched for pulsations in 118 unidentified pulsar-like sources, requiring about 10,000 years of CPU core time. In total, this survey has resulted in the discovery of 17 new gamma-ray pulsars, of which 13 are newly reported in this work, and an accompanying paper. These pulsars are all young, isolated pulsars with characteristic ages between 12 kyr and 2 Myr, and spin-down powers between 1034 and 4 × 1036 erg s−1. Two of these are the slowest spinning gamma-ray pulsars yet known. One pulsar experienced a very large glitch during the Fermi mission. In this, the first of two associated papers, we describe the search scheme used in this survey, and estimate the sensitivity of our search to pulsations in unidentified Fermi-LAT sources. One such estimate results in an upper limit of 57% for the fraction of pulsed emission from the gamma-ray source associated with the Cas A supernova remnant, constraining the pulsed gamma-ray photon flux that can be produced by the neutron star at its center. We also present the results of precise timing analyses for each of the newly detected pulsars.
Paclitaxel is currently only available as an intravenous (i.v.) formulation. DHP107 is a novel oral formulation of lipid ingredients and paclitaxel. DHP107 demonstrated comparable efficacy, safety, ...and pharmacokinetics to i.v. paclitaxel as a second-line therapy in patients with advanced gastric cancer (AGC). DREAM is a multicenter, open-label, prospective, randomized phase III study of patients with histologically/cytologically confirmed, unresectable/recurrent AGC after first-line therapy failure.
Patients were randomized 1:1 to DHP107 (200mg/m2 orally twice daily days 1, 8, 15 every 4weeks) or i.v. paclitaxel (175mg/m2 day 1 every 3weeks). Patients were stratified by Eastern Cooperative Oncology Group performance status, disease status, and prior treatment; response was assessed (Response Evaluation Criteria in Solid Tumors) every 6weeks. Primary end point: non-inferiority of progression-free survival (PFS); secondary end points: overall response rate (ORR), overall survival (OS), and safety. For the efficacy analysis, sequential tests for non-inferiority were carried out, first with a non-inferiority margin of 1.48, then with a margin of 1.25.
Baseline characteristics were balanced in the 236 randomized patients (n=118 per arm). Median PFS (per-protocol) was 3.0 (95% CI 1.7–4.0) months for DHP107 and 2.6 (95% CI 1.8–2.8) months for paclitaxel (hazard ratio HR=0.85; 95% CI 0.64–1.13). A sensitivity analysis on PFS using independent central review showed similar results (HR=0.93; 95% CI 0.70–1.24). Median OS (full analysis set) was 9.7 (95% CI 7.1−11.5) months for DHP107 versus 8.9 (95% CI 7.1–12.2) months for paclitaxel (HR=1.04; 95% CI 0.76–1.41). ORR was 17.8% for DHP107 (CR 4.2%; PR 13.6%) versus 25.4% for paclitaxel (CR 3.4%; PR 22.0%). Nausea, vomiting, diarrhea, and mucositis were more common with DHP107; peripheral neuropathy was more common with paclitaxel. There were only few Grade≥3 adverse events, most commonly neutropenia (42% versus 53%); febrile neutropenia was reported infrequently (5.9% versus 2.5%). No hypersensitivity reactions occurred with DHP107 (paclitaxel 2.5%).
DHP107 as a second-line treatment of AGC was non-inferior to paclitaxel for PFS; other efficacy and safety parameters were comparable. DHP107 is the first oral paclitaxel with proven efficacy/safety for the treatment of AGC.
NCT01839773.
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