OBJECTIVE:The phase II randomized controlled trial aimed to compare the outcomes of robot-assisted surgery with those of laparoscopic surgery in the patients with rectal cancer.
BACKGROUND:The ...feasibility of robot-assisted surgery over laparoscopic surgery for rectal cancer has not been established yet.
METHODS:Between February 21, 2012 and March 11, 2015, patients with rectal cancer (cT1-3NxM0) were enrolled. Patients were randomized 1:1 to either robot-assisted or laparoscopic surgery, and stratified per sex and administration of preoperative chemoradiotherapy. The primary outcome was the quality of total mesorectal excision (TME) specimen. Secondary outcomes were the circumferential and distal resection margins, the number of harvested lymph nodes, morbidity, bowel function recovery, and quality of life.
RESULTS:A total of 163 patients were randomly assigned to the robot-assisted (n = 81) and laparoscopic (n = 82) surgery groups, and 139 patients were eligible for the analyses (73 vs 66, respectively). One patient (1.2%) in the robot-assisted group was converted to open surgery. The TME quality did not differ between the robot-assisted and laparoscopic groups (80.3% vs 78.1% complete TME, respectively; 18.2% vs 21.9% nearly complete TME, respectively; P = 0.599). The resection margins, number of harvested lymph nodes, morbidity, and bowel function recovery also were not significantly different. On analyzing quality of life, scores of the European Organization for Research and Treatment of Cancer Quality of Life (EORTC QLQ C30) and EORTC QLQ CR38 were similar in the 2 groups, but in the EORTC QLQ CR 38 questionnaire, sexual function 12 months postoperatively was better in the robot-assisted group than in the laparoscopic group (P = 0.03).
CONCLUSIONS:Robot-assisted surgery in rectal cancer showed TME quality comparable with that of laparoscopic surgery, and it demonstrated similar postoperative morbidity, bowel function recovery, and quality of life.
Given environmental friendliness, high‐temperature proton exchange membrane fuel cells (HT‐PEMFCs) can be the alternative power source for clean power generation. However, neither developments nor ...strategies of diffusion media are actively conducted yet to achieve high‐performance HT‐PEMFCs. Herein, a nanoporous carbon nanotube (CNT) sheet, a new anode diffusion layer between the gas diffusion layer|bipolar plate interface that improves fuel cell performance and durability by CNT purification for facilitating fuel accessibility with uniform interfacial contact for reducing acid loss, is reported. Configuration of the optimal CNT‐inserted fuel cell is examined and proposed under the operating temperature of 140–200 °C. The underlying mechanism of this new diffusion layer with multiphysics simulation elucidates that the nanoporous nature induces gas‐wall collision, enabling uniform dispersion within adjacent diffusion media. These fuel cells outperform performance over two times higher and have a voltage decay rate nearly two times lower than conventional HT‐PEMFC.
A purified nanoporous carbon nanotube (CNT) sheet with few impurities is synthesized and inserted between the anode gas diffusion media and bipolar plate. The CNT‐inserted fuel cell notably improves performance and durability. Fuel cell testing combined with multiphysics simulation reveals that optimal nanoporous media increases gas‐wall collision, thereby achieving uniform gas dispersion in the fuel cell.
Summary Background The role of adjuvant chemotherapy for patients with rectal cancer is controversial, especially when used after preoperative chemoradiotherapy. Fluoropyrimidine-based adjuvant ...chemotherapy, including fluorouracil and leucovorin, has been widely used; however, the addition of oxaliplatin to fluorouracil and leucovorin (FOLFOX), a standard adjuvant regimen for colon cancer, has not been tested in rectal cancer. We aimed to compare the efficacy and safety of adjuvant fluorouracil and leucovorin with that of FOLFOX in patients with locally advanced rectal cancer after preoperative chemoradiotherapy. Methods In this open-label, multicentre, phase 2, randomised trial, patients with postoperative pathological stage II (ypT3–4N0) or III (ypTany N1–2) rectal cancer after preoperative fluoropyrimidine-based chemoradiotherapy and total mesorectal excision were recruited and randomly assigned (1:1) via a web-based software platform to receive adjuvant chemotherapy with either four cycles of fluorouracil and leucovorin (fluorouracil 380 mg/m2 and leucovorin 20 mg/m2 on days 1–5, every 4 weeks) or eight cycles of FOLFOX (oxaliplatin 85 mg/m2 , leucovorin 200 mg/m2 , and fluorouracil bolus 400 mg/m2 on day 1, and fluorouracil infusion 2400 mg/m2 for 46 h, every 2 weeks). Stratification factors were pathological stage (II vs III) and centre. Neither patients nor investigators were masked to group assignment. The primary endpoint was 3-year disease-free survival, analysed by intention to treat. This study is fully enrolled, is in long-term follow-up, and is registered with ClinicalTrials.gov , number NCT00807911. Findings Between Nov 19, 2008, and June 12, 2012, 321 patients were randomly assigned to fluorouracil and leucovorin (n=161) and FOLFOX (n=160). 141 (95%) of 149 patients in the fluorouracil plus leucovorin group and 141 (97%) of 146 in the FOLFOX group completed all planned cycles of adjuvant treatment. Median follow-up was 38·2 months (IQR 26·4–50·6). 3-year disease-free survival was 71·6% (95% CI 64·6–78·6) in the FOLFOX group and 62·9% (55·4–70·4) in the fluorouracil plus leucovorin group (hazard ratio 0·657, 95% CI 0·434–0·994; p=0·047). Any grade neutropenia, thrombocytopenia, fatigue, nausea, and sensory neuropathy were significantly more common in the FOLFOX group than in the fluorouracil plus leucovorin group; however, we noted no significant difference in the frequency of these events at grade 3 or 4. The most common grade 3 or worse adverse events were neutropenia (38 26% of 149 patients in the fluorouracil plus leucovorin group vs 52 36% of 146 patients in the FOLFOX group), leucopenia (eight 5% vs 12 8%), febrile neutropenia (four 3% vs one <1%), diarrhoea (four 3% vs two 1%), and nausea (one <1% vs two 1%). Interpretation Adjuvant FOLFOX improves disease-free survival compared with fluorouracil plus leucovorin in patients with locally advanced rectal cancer after preoperative chemoradiotherapy and total mesorectal excision, and warrants further investigation. Funding Korea Healthcare Technology R&D Project (South Korean Ministry of Health and Welfare).
Recently, addressing various wounds, ranging from skin injuries to pressure and chronic ulcers, has necessitated a more detailed approach to wound condition monitoring aimed at enhancing the ...patient's quality of life. Although most available wound dressings offer protection and promote the regeneration of wound lesions, they fail to monitor wound progression. To meet this need, this study introduces a pioneering solution: a wireless, battery‐free, optoelectronic diagnostic sensor seamlessly integrated into a colorimetric, pH‐sensitive wound dressing, designed to significantly enhance patient quality of life through improved wound care. Curcumin‐polycaprolactone (C‐PCL) dressing protect the wounds, promote cell regeneration, and possess antimicrobial properties. In addition, the dressing exhibits colorimetric pH‐monitoring capabilities across different wound conditions, enabling individuals without specialized knowledge to assess the status of their wounds. The core innovation lies in the integration of a green light‐emitting diode (LED) and photodiode, which meticulously evaluates color changes from yellow to red of colorimetric dressing, enhance the precision of this user‐friendly colorimetric diagnosis strategy. The integration of wireless battery‐free systems facilitates quantitative and real‐time monitoring of wound data in patients without inconvenience. These innovations will pave the way for rapid wound status evaluation, ensuring timely interventions and optimized care for deteriorating wound conditions.
The manuscript introduces an advanced wound care approach: a wireless, battery‐free optoelectronic diagnostic sensor integrated with a colorimetric electrospun nanofiber wound dressing. The innovative strategy employs a Curcumin‐polycaprolactone (C‐PCL) based dressing that changes color in response to pH variations, indicating evolving wound conditions. The integration of an optoelectronic sensor and colorimetric wound dressing for wireless data transmission distinguishes this work.
Background
In East Asia, S-1 plus cisplatin (SP) is one of the standard first-line chemotherapy regimens for metastatic or recurrent gastric cancer (MRGC). Oxaliplatin is generally less toxic and ...more convenient to administer than cisplatin.
Patients and methods
This was a multicenter, phase III study assessing whether S-1/oxaliplatin (SOX) was non-inferior/superior to SP in terms of progression-free survival (PFS). Patients with MRGC were randomized 1:1 to receive either SOX (S-1 80 mg/m
2
/day on days 1–14; oxaliplatin 130 mg/m
2
on day 1; every 3 weeks) or SP (S-1 80 mg/m
2
/day on days 1–14; cisplatin 60 mg/m
2
on day 1; every 3 weeks SP3).
Results
Between October 2012 and October 2014, 338 patients were randomized. The median age was 56 years, and 51% of patients had measurable lesions. SOX was significantly non-inferior but not superior to SP3 in terms of PFS median 5.6 versus 5.7 months; hazard ratio (HR) 0.85; 95% confidence interval (CI) 0.67–1.07. In patients with measurable disease, objective response rates were similar between SOX and SP3 (58% versus 60%). Overall, the survival in both groups did not differ (median 12.9 versus 11.4 months; HR 0.86; 95% CI 0.66–1.11). Treatment was well tolerated in both arms. Anemia, leucopenia, neutropenia, febrile neutropenia, and oral mucositis were more common with SP3. In contrast, thrombocytopenia, nausea, vomiting, and peripheral neuropathy were more common with SOX.
Conclusions
SOX was non-inferior to SP3. The two regimens were well tolerated with different toxicity profiles. The SOX regimen can be recommended as a first-line treatment for MRGC.
Trial registration
ClinicalTrials.gov: NCT01671449
Summary Background Compared with open resection, laparoscopic resection of rectal cancers is associated with improved short-term outcomes, but high-level evidence showing similar long-term outcomes ...is scarce. We aimed to compare survival outcomes of laparoscopic surgery with open surgery for patients with mid-rectal or low-rectal cancer. Methods The Comparison of Open versus laparoscopic surgery for mid or low REctal cancer After Neoadjuvant chemoradiotherapy (COREAN) trial was an open-label, non-inferiority, randomised controlled trial done between April 4, 2006, and Aug 26, 2009, at three centres in Korea. Patients (aged 18–80 years) with cT3N0–2M0 mid-rectal or low-rectal cancer who had received preoperative chemoradiotherapy were randomly assigned (1:1) to receive either open or laparoscopic surgery. Randomisation was stratified by sex and preoperative chemotherapy regimen. Investigators were masked to the randomisation sequence; patients and clinicians were not masked to the treatment assignments. The primary endpoint was 3 year disease-free survival, with a non-inferiority margin of 15%. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov , number NCT00470951. Findings We randomly assigned 340 patients to receive either open surgery (n=170) or laparoscopic surgery (n=170). 3 year disease-free survival was 72·5% (95% CI 65·0–78·6) for the open surgery group and 79·2% (72·3–84·6) for the laparoscopic surgery group, with a difference that was lower than the prespecified non-inferiority margin (–6·7%, 95% CI −15·8 to 2·4; p<0·0001). 25 (15%) patients died in the open group and 20 (12%) died in the laparoscopic group. No deaths were treatment related. Interpretation Our results show that laparoscopic resection for locally advanced rectal cancer after preoperative chemoradiotherapy provides similar outcomes for disease-free survival as open resection, thus justifying its use. Funding National Cancer Center, South Korea.
PURPOSE
We evaluated the role of oxaliplatin as adjuvant chemotherapy in patients with rectal cancer who received preoperative chemoradiotherapy (CRT) with fluoropyrimidine monotherapy and total ...mesorectal excision (TME).
METHODS
The ADORE trial (adjuvant oxaliplatin in rectal cancer) is a multicenter, randomized trial in patients with postoperative ypStage II (ypT3-4N0) or III (ypT
any
N1-2) rectal cancer after fluoropyrimidine-based preoperative CRT and TME. Patients were randomly assigned (1:1) to receive adjuvant chemotherapy either with FL (fluorouracil 380 mg/m
2
and leucovorin 20 mg/m
2
) or FOLFOX (oxaliplatin 85 mg/m
2
, leucovorin 200 mg/m
2
, and fluorouracil bolus 400 mg/m
2
on day 1, fluorouracil infusion 2,400 mg/m
2
for 46 hours). Stratification factors included ypStage and participating center. Primary end point was disease-free survival (DFS).
RESULTS
A total of 321 patients were enrolled between November 19, 2008, and June 12, 2012. Six-year DFS rates were 68.2% in the FOLFOX arm versus 56.8% in the FL arm, with a stratified hazard ratio of 0.63 (95% CI, 0.43 to 0.93; P = .018) by intention-to-treat analysis. In the subgroup analysis for DFS, FOLFOX was favorable versus FL in patients with ypStage III, ypN1b, ypN2, high-grade histology, minimally regressed tumor, and an absence of lymphovascular or perineural invasion. Six-year overall survival rate was 78.1% in the FOLFOX arm versus76.4% in the FL arm (hazard ratio, 0.73; 95% CI, 0.45 to 1.19; P = .21). In the subgroup analysis for OS, FOLFOX was favorable versus FL in patients with ypN2 and minimally regressed tumor.
CONCLUSION
Adjuvant FOLFOX improved DFS in patients with rectal cancer with ypStage II and III disease after preoperative CRT. Adjuvant FOLFOX may be considered on the basis of the postoperative pathologic stage in those who received preoperative CRT and TME.
Abstract
Motivation
Blockade of the human ether-à-go-go-related gene (hERG) channel by small compounds causes a prolonged QT interval that can lead to severe cardiotoxicity and is a major cause of ...the many failures in drug development. Thus, evaluating the hERG-blocking activity of small compounds is important for successful drug development. To this end, various computational prediction tools have been developed, but their prediction performances in terms of sensitivity and negative predictive value (NPV) need to be improved to reduce false negative predictions.
Results
We propose a computational framework, DeepHIT, which predicts hERG blockers and non-blockers for input compounds. For the development of DeepHIT, we generated a large-scale gold-standard dataset, which includes 6632 hERG blockers and 7808 hERG non-blockers. DeepHIT is designed to contain three deep learning models to improve sensitivity and NPV, which, in turn, produce fewer false negative predictions. DeepHIT outperforms currently available tools in terms of accuracy (0.773), MCC (0.476), sensitivity (0.833) and NPV (0.643) on an external test dataset. We also developed an in silico chemical transformation module that generates virtual compounds from a seed compound, based on the known chemical transformation patterns. As a proof-of-concept study, we identified novel urotensin II receptor (UT) antagonists without hERG-blocking activity derived from a seed compound of a previously reported UT antagonist (KR-36676) with a strong hERG-blocking activity. In summary, DeepHIT will serve as a useful tool to predict hERG-induced cardiotoxicity of small compounds in the early stages of drug discovery and development.
Availability and implementation
https://bitbucket.org/krictai/deephit and https://bitbucket.org/krictai/chemtrans
Supplementary information
Supplementary data are available at Bioinformatics online.
Purpose
Nonunion is the most frequent cause of reoperation and is associated with high morbidity after distal femur fracture (DFF). We examined the rates of nonunion requiring reoperation after ...fixation for DFF using a locking compression plate (LCP) or retrograde intramedullary nail (RIMN).
Methods
We included four studies comparing LCP and RIMN and 38 single-cohort studies reporting LCP or RIMN. In total, 2156 femurs were included and 166 non-unions were detected. We conducted a pair-wise meta-analysis (with a fixed-effects model) on the four comparative studies and a proportional meta-analysis on the 38 articles to estimate the nonunion rate. We performed sensitivity analysis by comparing studies using LCP with less invasive surgical systems (LISS) with those that used RIMN.
Results
The pairwise meta-analysis showed a similar nonunion rate between the groups odds ratio: 1.02; 95% confidence interval (CI) 0.94–1.11,
p
= 0.633. According to proportional meta-analysis, the pooled prevalence of nonunion was 5% (95% CI 4–7) totally, 6% (95% CI 4–8) in the LCP group, and 4% (95% CI 2–6) in the RIMN group (heterogeneity:
p
= 0.105). According to the sensitivity analysis, there was no difference in the union rate. The pooled prevalence of nonunion from sensitivity analysis was 4 % (95% CI, 3–5); it was 4% (95% CI, 3–6) in LCP with LISS and was 4% (95% CI, 2–6) in RIMN group (heterogeneity:
p
= 0.941).
Conclusion
Approximately 5% of patients who underwent LCP or RIMN fixation developed nonunion. Therefore, LCP and RIMN are effective DFF techniques and mastering one of them is essential.
Electroencephalography (EEG) captures minute electrical signals emanating from the brain. These signals are vulnerable to interference from external noise and dynamic artifacts; hence, accurately ...recording such signals is challenging. Although dry electrodes are convenient, their signals are of limited quality; consequently, wet electrodes are predominantly used in EEG. Therefore, developing dry electrodes for accurately and stably recording EEG signals is crucial. In this study, we developed flexible dry electrodes using polydimethylsiloxane (PDMS)/carbon-nanotube (CNT) composites with isotropically wrinkled surfaces that effectively combine the advantages of wet and dry electrodes. Adjusting the PDMS crosslinker ratio led to good adhesion, resulting in a highly adhesive CNT/PDMS composite with a low Young's modulus that exhibited excellent electrical and mechanical properties owing to its ability to conformally contact skin. The isotropically wrinkled surface also effectively controls dynamic artifacts during EEG signal detection and ensures accurate signal analysis. The results of this study demonstrate that dry electrodes based on flexible CNT/PDMS composites and corrugated structures can outperform wet electrodes. The introduction of such electrodes is expected to enable the accurate analysis and monitoring of EEG signals in various scenarios, including clinical trials.
PDF
