There is a need for effective wound healing through rapid wound closure, reduction of scar formation, and acceleration of angiogenesis. Hydrogel is widely used in tissue engineering, but it is not an ...ideal solution because of its low vascularization capability and poor mechanical properties. In this study, gelatin methacrylate (GelMA) was tested as a viable option with tunable physical properties. GelMA hydrogel incorporating a vascular endothelial growth factor (VEGF) mimicking peptide was successfully printed using a three-dimensional (3D) bio-printer owing to the shear-thinning properties of hydrogel inks. The 3D structure of the hydrogel patch had high porosity and water absorption properties. Furthermore, the bioactive characterization was confirmed by cell culture with mouse fibroblasts cell lines (NIH 3T3) and human umbilical vein endothelial cells. VEGF peptide, which is slowly released from hydrogel patches, can promote cell viability, proliferation, and tubular structure formation. In addition, a pig skin wound model was used to evaluate the wound-healing efficacy of GelMA-VEGF hydrogel patches; the results suggest that the GelMA-VEGF hydrogel patch can be used for wound dressing.
There has been reported that the association between nodal spread and tumor size was disrupted in triple-negative breast cancer (TNBC) and it showed characteristically early relapse. The TNM ...(tumor–node–metastasis) staging system might not be equally effective as a prognostic indicator for all subtypes. The aim of our study was to evaluate the usefulness of the staging according to subtypes.
We conducted a retrospective analysis of invasive breast cancer patients who received curative surgery at Samsung Medical Center from 2000 to 2004. Relapse-free survivals (RFS) by stage were analyzed.
Thousand eight hundred and seventy-nine patients who were available clinicopathologic data were included. These patients were divided into three subtypes: hormone receptor (HR)+, human epidermal growth factor receptor 2+, and triple negative groups. As the stage became more advanced, the slope of each stage of the RFS curves of patients with HR+ and HER2+ steadily increased. In contrast, RFS curves intermingled and showed overlap from stage 1 to 3A in TNBC patients. There was only wide separation of RFS curves between stage 1-3A and 3B-3C in TNBC.
The current TNM staging system might not be enough for encompassing the tumor biology and for predicting outcomes to make therapeutic decisions for all BCs, especially for TNBC patients.
Ferroelectric and magnetic materials are a time-honoured subject of study and have led to some of the most important technological advances to date. Magnetism and ferroelectricity are involved with ...local spins and off-centre structural distortions, respectively. These two seemingly unrelated phenomena can coexist in certain unusual materials, termed multiferroics. Despite the possible coexistence of ferroelectricity and magnetism, a pronounced interplay between these properties has rarely been observed. This has prevented the realization of multiferroic devices offering such functionality. Here, we report a striking interplay between ferroelectricity and magnetism in the multiferroic TbMn2O5, demonstrated by a highly reproducible electric polarization reversal and permanent polarization imprint that are both actuated by an applied magnetic field. Our results point to new device applications such as magnetically recorded ferroelectric memory.
Once regarded as a smoker's disease, small-cell lung cancer (SCLC) has been occasionally detected in never-smokers as smoking rates decrease worldwide. We investigated the clinical and genetic ...characteristics of SCLC in never-smokers.
Patients diagnosed with SCLC were grouped into smokers and never-smokers. The clinical outcomes of the two groups were compared. For SCLC in never-smokers, somatic mutation profiling was carried out using the AmpliSeq™ Cancer Hotspot Panel v2 and semiconductor sequencing technology. Epidermal growth factor receptor (EGFR) mutation was confirmed by PNAClamp™.
In total, 391 SCLC patients treated over a 5-year period were analyzed. Fifty patients (13%) were never-smokers. The median overall survival was 18.2 months in never-smokers and 13.1 months in smokers (P = 0.054). Never-smoking history was independently a good prognostic factor hazard ratio = 0.645, 95% confidence interval (CI) 0.456–0.914, as were limited disease (HR = 0.372, 95% CI 0.294–0.471), and lower age (HR = 0.709, 95% CI 0.566–0.888). The objective response rates to first-line etoposide/cisplatin therapy were similar between never-smokers and smokers (75% versus 81%). Of 28 genetically evaluable never-smokers, EGFR mutations were detected in four cases (two L858R, one deletion in exon 19, and one G719A). Other mutations were in TP53 (n = 26), RB1 (n = 7), PTEN (n = 5), MET (n = 4), and SMAD4 (n = 3).
Never-smokers with SCLC are increasingly prevalent and have a better prognosis than smokers with SCLC in Korea. Our study warrants further investigation in this group.
In this study, we undertook a randomized phase III trial of 105 NSCLC patients with oligo (one to four) -brain metastases. Patients were randomly assigned (1:1) to receive either stereotactic ...radiosurgery (SRS) followed by chemotherapy or upfront chemotherapy alone. The results demonstrated that SRS followed by chemotherapy did not improve overall survival compared with upfront chemotherapy only.
It is unclear whether treating brain metastasis before starting systemic chemotherapy can improve survival compared with upfront chemotherapy in non-small-cell lung cancer (NSCLC) with asymptomatic cerebral oligo-metastases.
We undertook a randomized, controlled trial of 105 patients with one to four brain metastases, admitted to Samsung Medical Center between 2008 and 2013. Patients were randomly assigned to receive stereotactic radiosurgery (SRS) (49 patients) followed by chemotherapy or upfront chemotherapy (49 patients). The primary end point was overall survival (OS) and secondary end points included central nervous system (CNS) progression-free survival, progression to symptomatic brain metastasis and brain functional outcome.
The median age was 58 years (range, 29–85) with ECOG 0–1 performance status, and 40% of patients were never smokers. Most patients had adenocarcinoma, and about half of patients had only one brain metastasis, while the rest had multiple cerebral metastases. The median OS time was 14.6 months 95% confidence interval (CI), 9.2–20.0 in the SRS group and 15.3 months (95% CI, 7.2–23.4) for the upfront chemotherapy group (P = 0.418). There was no significant difference in time to CNS disease progression median, 9.4 months (SRS) versus 6.6 months (upfront chemotherapy),P = 0.248. Symptomatic progression of brain metastases was observed more frequently in the upfront chemotherapy group (26.5%) than the SRS group (18.4%) but without statistical significance.
Although this study included smaller sample size than initially anticipated due to early termination, SRS followed by chemotherapy did not improve OS in oligo-brain metastases NSCLC patients compared with upfront chemotherapy. Further study with large number of patients should be needed to confirm the use of upfront chemotherapy alone in this subgroup of patients.
NCT01301560.
•Investigator-assessed PFS data in the ALEX study are now mature (53% of events in the alectinib arm).•Alectinib significantly prolonged PFS vs crizotinib (stratified HR 0.43, 95% CI 0.32–0.58; ...median 34.8 vs 10.9 months).•OS data are immature (37% of events); median NR alectinib vs 57.4 months crizotinib (stratified HR 0.67, 95% CI 0.46–0.98).•5-year OS rate of 62.5% with alectinib and 45.5% with crizotinib.•Median treatment duration was longer with alectinib (28.1 vs 10.8 months crizotinib), with no new safety signals seen.
The ALEX study demonstrated significantly improved progression-free survival (PFS) with alectinib versus crizotinib in treatment-naive ALK-positive non-small-cell lung cancer (NSCLC) at the primary data cut-off (9 February 2017). We report mature PFS (cut-off: 30 November 2018) and overall survival (OS) data up to 5 years (cut-off: 29 November 2019).
Patients with stage III/IV ALK-positive NSCLC were randomized to receive twice-daily alectinib 600 mg (n = 152) or crizotinib 250 mg (n = 151) until disease progression, toxicity, withdrawal or death. Primary end point: investigator-assessed PFS. Secondary end points included objective response rate, OS and safety.
Mature PFS data showed significantly prolonged investigator-assessed PFS with alectinib hazard ratio (HR) 0.43, 95% confidence interval (CI) 0.32–0.58; median PFS 34.8 versus 10.9 months crizotinib. Median duration of OS follow-up: 48.2 months alectinib, 23.3 months crizotinib. OS data remain immature (37% of events). Median OS was not reached with alectinib versus 57.4 months with crizotinib (stratified HR 0.67, 95% CI 0.46–0.98). The 5-year OS rate was 62.5% (95% CI 54.3–70.8) with alectinib and 45.5% (95% CI 33.6–57.4) with crizotinib, with 34.9% and 8.6% of patients still on study treatment, respectively. The OS benefit of alectinib was seen in patients with central nervous system metastases at baseline HR 0.58 (95% CI 0.34–1.00) and those without HR 0.76 (95% CI 0.45–1.26). Median treatment duration was longer with alectinib (28.1 versus 10.8 months), and no new safety signals were observed.
Mature PFS data from ALEX confirmed significant improvement in PFS for alectinib over crizotinib in ALK-positive NSCLC. OS data remain immature, with a higher 5-year OS rate with alectinib versus crizotinib. This is the first global randomized study to show clinically meaningful improvement in OS for a next-generation tyrosine kinase inhibitor versus crizotinib in treatment-naive ALK-positive NSCLC.
NCT02075840.
Summary
Background Giant congenital melanocytic naevi (GCMN) are known risk factors for the development of melanoma. However, melanoma risk among Asians is rarely evaluated.
Objectives To evaluate ...the clinical characteristics and risk of melanoma development from GCMN in Koreans, we performed a nationwide retrospective cohort study in Korea. GCMN were defined as those comprising ≥ 5% body surface area in children or measuring ≥ 20 cm in adults.
Methods In total, 131 patients with GCMN were enrolled, with a mean age of 10·3 years (range: birth–70 years).
Results The posterior trunk was the most common site (67, 51·1%), followed by lateral trunk, anterior trunk, legs, both anterior and posterior trunk, buttocks, and arms. Satellite naevi were present in 69 cases (52·7%), and axial areas were more commonly involved in patients with satellite naevi than in those without satellite lesions. Atypical features such as rete ridge elongation and bridges were seen, and, among these, pagetoid spread and ballooning cell changes were more common in patients < 4 years old. Proliferative nodules were found in three cases. Melanomas had developed in three of 131 patients (2·3%; a 6‐year‐old girl, a 14‐year‐old girl and a 70‐year‐old man), and the incidence rate was 990 per 100 000 person‐years. Melanomas in these three patients consisted of two cutaneous melanomas and one extracutaneous meningeal melanoma.
Conclusions We should be aware of melanoma development from GCMN, and lifelong follow‐up is required due to the risk of melanoma arising in GCMN.
Using zinc nitrate as precursors and NaOH starch as a stabilizing agent, hexagonal zinc oxide (ZnO) nanoparticles has been synthesized by precipitation method. Display omitted
► Synthesized hexagonal ...ZnO nanoparticles by precipitation method using ZnNO3 and NaOH starch. ► Report frequency dependence dielectric anomaly at low temperature (85–300K) in ZnO nanoparticles. ► Enhancement of the dielectric response of ZnO nanoparticles in the low-frequency range.
Using zinc nitrate as a precursor and NaOH starch as a stabilizing agent, hexagonal zinc oxide (ZnO) nanoparticles has been synthesized by precipitation method. The transmission electron microscopy (TEM) images show particles of nearly uniform spherical size of around 40nm. The infrared spectroscopy (FT-IR) measurement reveals the peak at 500cm−1, corresponding to the Zn–O bond. Dielectric studies of ZnO nanoparticles show frequency dependence dielectric anomaly at low temperature (85–300K). Results reveal that the capacitance and loss tangent decrease with the frequency while these parameters improve with the increasing of temperature. The increase of a.c. conductivity with the temperature indicates that the mobility of charge carriers is responsible for hopping and electronic polarization in ZnO nanoparticles.
This study was performed to assess whether intubation is more difficult in obese patients and to assess the ability of a new index: the ratio of the neck circumference to thyromental distance ...(NC/TM), to predict difficult intubation in obese patients.
The incidence of difficult tracheal intubation in 123 obese (BMI≥27.5 kg m−2) and 125 non-obese patients was compared. Difficult intubation was determined using the intubation difficulty scale (IDS≥5). The NC/TM ratio was calculated and its ability to predict difficult intubation in obese patients was compared with that of established predictors including high BMI, the Mallampati score, the Wilson score, NC, width of mouth opening, sternomental distance, TM, and a previous history of difficult intubation.
Difficult intubation was more frequent in obese patients than in non-obese patients (13.8% vs 4.8%; P=0.016). Multivariate analysis revealed that the Mallampati score, the Wilson score, and NC/TM independently predicted difficult intubation in obese patients. Among these three indices, NC/TM showed the highest sensitivity and a negative predictive value, and largest area under the curve on an ROC curve.
Difficult intubation was more common in obese patients and the NC/TM was a better method for predicting difficult intubation than other established indices.
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