To compare the long-term survival outcomes between laparoscopic radical hysterectomy (LRH) and open radical hysterectomy (ORH).
We matched patients with stage IA2 to IIA cervical cancer with known ...risk factors for recurrence who underwent ORH and LRH.
Compared with ORH (n = 263), LRH (n = 263) did not have higher risks of recurrence hazard ratio (HR) = 1.28; 95% confidence interval (CI) 0.62–2.64 or death (HR = 1.46; 95% CI 0.62–3.43). Even in patients with tumors >2 cm in diameter, the risks of recurrence (HR = 0.82; 95% CI 0.31–2.16) or death (HR = 1.01; 95% CI 0.35–2.95) were not higher for LRH than for ORH. The LRH and ORH group had 5-year recurrence-free survival rates of 92.8% and 94.4%, respectively (P = 0.499). LRH resulted in significantly lower estimated blood loss (379.6 versus 541.1 ml, P < 0.001) and shorter postoperative hospital stay (12.5 versus 20.3 days, P < 0.001). Intraoperative complication rates were similar in the two groups (6.8% versus 5.7%, P = 0.711), but postoperative complication rate was lower in the LRH than in the ORH group (9.2% versus 21%, P < 0.001).
LRH is an oncologically safe alternative to ORH and was associated with fewer postoperative complication and earlier recovery.
The aim of this retrospective study was to assess the efficacy of recombinant human bone morphogenetic protein-2 (rhBMP-2) with hydroxyapatite (HA) granules and fibrin sealant (FS) in maxillary sinus ...floor augmentation (MSFA), with a focus on the volume change. Fifty-two of 137 patients who underwent MSFA with rhBMP-2/HA grafting between June 2016 and December 2022 met the study inclusion criteria; 25 had received rhBMP-2/HA without FS and 27 had received rhBMP-2/HA with FS. Computed tomography (CT) images were obtained preoperatively, immediately following the operation, and at 6 months postoperative. These images were three-dimensionally reconstructed to measure the volumetric and height changes following MSFA. The mean ± standard deviation percentage of volumetric change at 6 months was 48.75 ± 37.44% in the group with FS and 29.77 ± 13.42% in the group without FS (P = 0.019). The vertical height measured at a specific site of the grafted area showed a mean percentage change at 6 months of 4.05 ± 12.08% in the group with FS and 6.07 ± 10.15% in the group without FS (P = 0.518). The additional use of FS as a carrier for rhBMP-2/HA in MSFA was found to improve surgical convenience and bone regeneration ability.
Summary
Background
Transient receptor potential vanilloid subfamily, member 1 (TRPV1) may play an important role in pruritus and inflammation induction in atopic dermatitis (AD). The treatment effect ...of TRPV1 antagonist via topical application in patients with AD remains unknown.
Objectives
To assess the clinical efficacy and safety of PAC‐14028, a TRPV1 antagonist, via topical application in patients with AD.
Methods
In this 8‐week, phase IIb, randomized, double‐blind, multicentre, vehicle‐controlled study, patients with mild‐to‐moderate AD were randomized to receive PAC‐14028 cream 0·1%, 0·3%, 1·0% or vehicle cream twice daily. The primary efficacy end point was the Investigator's Global Assessment (IGA) success rate defined as the percentage of patients with an IGA score of 0 or 1 at week 8. The secondary efficacy end points included the severity Scoring of Atopic Dermatitis (SCORAD) index and Eczema Area and Severity Index (EASI) 75/90.
Results
A total of 194 patients were enrolled. IGA success rates at week 8 were 14·58% for vehicle cream, 42·55% for PAC‐14028 cream 0·1% (P = 0·0025 vs. vehicle), 38·30% for PAC‐14028 cream 0·3% (P = 0·0087 vs. vehicle) and 57·45% for PAC‐14028 cream 1·0% (P < 0·001 vs. vehicle). In particular, statistically significant differences were found between the vehicle and treatment groups in the IGA success rates with two‐grade improvement. The SCORAD index, EASI 75/90, sleep disturbance score and pruritus visual analogue scale showed a trend towards improvement. No significant safety issues were reported.
Conclusions
PAC‐14028 cream may be an effective and safe treatment modality for the treatment of patients with mild‐to‐moderate AD.
What is already known about this topic?
Atopic dermatitis (AD) is one of the most common inflammatory skin diseases characterized by pruritic erythematous skin lesions and barrier dysfunction.
Transient receptor potential vanilloid subfamily, member 1 (TRPV1) antagonists suppress the release of pruritic and proinflammatory mediators.
The preclinical results demonstrate the feasibility of TRPV1 as a potential therapeutic target for the treatment of AD.
What does this study add?
TRPV1 regulates inflammation and pruritus in patients with AD.
PAC‐14028 cream, a novel TRPV1 antagonist, was superior to vehicle in improving clinical symptoms and signs with a favourable safety profile in adults with mild‐to‐moderate AD.
TRPV1 antagonism may play a role as a promising nonsteroidal topical treatment target for AD with a new mechanism of action.
Linked Editorial: Song and Armstrong. Br J Dermatol 2019; 180:971–972.
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IntroductionWhat adolescents watch affects their body image. Smartphone is one of the most used tool in them today, allowing users to interact each other and share not only pictures but also ...sights.ObjectivesThe aim of this study is to evaluate the relationship between time/purpose (i.e. social media or the others) of smartphone usage and body image distortion revealed by weight control behavior. Differences in the effect of smartphone usage according to gender was also evaluated.MethodsThe cross-sectional study obtained data from the 2017 Korea Youth Risk Behavior Web-based Survey, a nationally representative survey targeting middle and high school students (N=62,276). We categorized the time using a smartphone into 4 groups: less than 1 h, 1-2 h, 3-4 h, and 5 h or more a day. The students were divided into two groups according to whether their main purpose of using a smartphone is social media or not. We defined that adolescents have body image distortion when they attempted to lose weight in the last 30 days, even though they were not obese (BMI < 95th percentile). We classified inappropriate weight control behavior as using: fasting for at least 24 hours, taking over-the-counter diet pills, taking laxatives or diuretics, vomiting, and eating only one food. We performed logistic regression analysis to evaluate the association between time using a smartphone and body image distortion expressed as all kinds of weight control behavior, adjusting for age, gender, residential area, family economic status, hours of sleep, current alcohol consumption, smoking and day time activity. Furthermore, we repeated logistic regression analysis to evaluate the association between time using a smartphone and inappropriate weight control behavior. Analyses were also stratified according to gender and main purpose of using a smart phone.ResultsSmartphone usage time was significantly associated with body image distortion and inappropriate weight control behavior in total group and female adolescents (P <0.05). The association between inappropriate weight control behavior and smartphone usage time is significant even in male adolescent if they use a smartphone more than 5 hours a day. The association between inappropriate weight control and smartphone usage time is also significant when they are not obese. The odd ratio of inappropriate weight control behavior in not obesity group was higher when social media is the main purpose of using a smartphone than the others (OR 1.390 in total group, 1.491 in girls, P <0.001).ConclusionsUsing a smartphone and social media too much is associated with body image distortion and inappropriate weight control behavior in adolescents. It is necessary to reduce excessive smartphone use and educate media literacy for healthy body awareness.Disclosure of InterestNone Declared
This mixed methods study investigated how decent work is conceptualized and understood in South Korea by surveying 320 Korean working adults. Using a convergent parallel mixed methods design, ...qualitative and quantitative parts of the study were conducted concurrently. Emic conceptualizations of decent work were qualitatively explored, and compared with the quantitative findings from administrating the Korean-translated version of Duffy et al.'s (2017) Decent Work Scale. Internal consistency estimates for the Korean-Decent Work Scale (K-DWS) subscales ranged from 0.74 to 0.94, and the confirmatory factor analysis yielded a good fit for the 5-factor model (safe working conditions, access to healthcare, adequate compensation, free time and rest, and complementary values) to the data with South Korean participants. Evidence largely supported convergent, discriminant, and predictive validity of the scale. The bifactorial structure was similar to the original U.S. version, did not differ across age, but did differ across gender. A few differences are discussed through a cultural lens. Implications for future research are discussed.
•Qualitative findings largely corroborate the Psychology of Working Theory conceptualization of decent work.•Fifteen-item Korean Decent Work Scale (K-DWS) appears psychometrically sound.•Confirmatory factor analysis yielded a good fit for the original DWS 5-factor model.•K-DWS meaningfully predicts job satisfaction, work meaning, and withdrawal intentions.
Data are limited regarding the use of poly(adenosine diphosphate ADP-ribose) polymerase inhibitors, such as veliparib, in combination with chemotherapy followed by maintenance as initial treatment in ...patients with high-grade serous ovarian carcinoma.
In an international, phase 3, placebo-controlled trial, we assessed the efficacy of veliparib added to first-line induction chemotherapy with carboplatin and paclitaxel and continued as maintenance monotherapy in patients with previously untreated stage III or IV high-grade serous ovarian carcinoma. Patients were randomly assigned in a 1:1:1 ratio to receive chemotherapy plus placebo followed by placebo maintenance (control), chemotherapy plus veliparib followed by placebo maintenance (veliparib combination only), or chemotherapy plus veliparib followed by veliparib maintenance (veliparib throughout). Cytoreductive surgery could be performed before initiation or after 3 cycles of trial treatment. Combination chemotherapy was 6 cycles, and maintenance therapy was 30 additional cycles. The primary end point was investigator-assessed progression-free survival in the veliparib-throughout group as compared with the control group, analyzed sequentially in the
-mutation cohort, the cohort with homologous-recombination deficiency (HRD) (which included the
-mutation cohort), and the intention-to-treat population.
A total of 1140 patients underwent randomization. In the
-mutation cohort, the median progression-free survival was 34.7 months in the veliparib-throughout group and 22.0 months in the control group (hazard ratio for progression or death, 0.44; 95% confidence interval CI, 0.28 to 0.68; P<0.001); in the HRD cohort, it was 31.9 months and 20.5 months, respectively (hazard ratio, 0.57; 95 CI, 0.43 to 0.76; P<0.001); and in the intention-to-treat population, it was 23.5 months and 17.3 months (hazard ratio, 0.68; 95% CI, 0.56 to 0.83; P<0.001). Veliparib led to a higher incidence of anemia and thrombocytopenia when combined with chemotherapy as well as of nausea and fatigue overall.
Across all trial populations, a regimen of carboplatin, paclitaxel, and veliparib induction therapy followed by veliparib maintenance therapy led to significantly longer progression-free survival than carboplatin plus paclitaxel induction therapy alone. The independent value of adding veliparib during induction therapy without veliparib maintenance was less clear. (Funded by AbbVie; VELIA/GOG-3005 ClinicalTrials.gov number, NCT02470585.).
p130Cas regulates cancer progression by driving tyrosine receptor kinase signaling. Tight regulation of p130Cas expression is necessary for survival, apoptosis, and maintenance of cell motility in ...various cell types. Several studies revealed that transcriptional and post-translational control of p130Cas are important for maintenance of its expression and activity. To explore novel regulatory mechanisms of p130Cas expression, we studied the effect of microRNAs (miRs) on p130Cas expression in human breast cancer MCF7 cells. Here, we provide experimental evidence that miR-362-3p and miR-329 perform a tumor-suppressive function and their expression is downregulated in human breast cancer. miR-362-3p and miR-329 inhibited cellular proliferation, migration, and invasion, thereby suppressing tumor growth, by downregulating p130Cas. Ectopic expression of p130Cas attenuated the inhibitory effects of the two miRs on tumor progression. Relative expression levels of miR-362-3p/329 and p130Cas between normal and breast cancer correlated inversely; miR-362-3p/329 expression was decreased, whereas that of p130Cas increased in breast cancers. Furthermore, we showed that downregulation of miR-362-3p and miR-329 was caused by differential DNA methylation of miR genes. Enhanced DNA methylation (according to methylation-specific PCR) was responsible for downregulation of miR-362-3p and miR-329 in breast cancer. Taken together, these findings point to a novel role for miR-362-3p and miR-329 as tumor suppressors; the miR-362-3p/miR-329-p130Cas axis seemingly has a crucial role in breast cancer progression. Thus, modulation of miR-362-3p/miR-329 may be a novel therapeutic strategy against breast cancer.
To review the evidence for the efficacy and safety of biological agents in patients with rheumatoid arthritis (RA) to provide data to develop treatment recommendations by the European League Against ...Rheumatism (EULAR) Task Force.
Medline, Embase and Cochrane databases were searched for relevant articles on infliximab (IFX), etanercept (ETN), adalimumab (ADA), certolizumab-pegol (CZP), golimumab (GLM), anakinra (ANA), abatacept (ABT), rituximab (RTX) and tocilizumab (TCZ) published between 1962 and February 2009; published abstracts from the 2007-2008 American College of Rheumatology (ACR) and EULAR conference were obtained.
87 articles and 40 abstracts were identified. In methotrexate (MTX) naïve patients, biological therapy with IFX, ETN, ADA, GLM or ABT has been shown to improve clinical outcomes (level of evidence 1B). In MTX/other synthetic disease-modifying antirheumatic drug (DMARD) failures all nine biological agents confer benefit (1B), with lower efficacy noted for ANA. RTX, ABT, TCZ and GLM demonstrate efficacy in tumour necrosis factor inhibitor (TNFi) failures (1B). Less evidence exists for switching between IFX, ETN and ADA (3B). Biological and MTX combination therapy is more efficacious than a biological agent alone (1B). A safety review shows no increased malignancy risk compared with conventional DMARDs (3B). TNFi are generally associated with an increased risk of serious bacterial infection, particularly within the first 6 months of treatment initiation; increased tuberculosis (TB) rates with TNFi are highest with the monoclonal antibodies (3B).
There is good evidence for the efficacy of biological agents in patients with RA. Safety data confirm an increased risk of bacterial infection and TB with TNFi compared with conventional DMARDs.
To monitor progression to inflammatory arthritis (IA) in individuals with non-specific musculoskeletal (MSK) symptoms and positive anticyclic citrullinated peptide (anti-CCP) antibodies. To develop a ...pragmatic model to predict development of IA in this patient group.
In this prospective observational cohort, patients with new non-specific MSK symptoms and positive anti-CCP were recruited from regional primary care and secondary care referrals. Clinical, imaging and serological parameters were assessed at baseline. Cox regression analysis was performed to identify predictors of progression to IA and develop a risk score to stratify patients at presentation.
100 consecutive patients (73 women, mean age 51 years) were followed up for median 19.8 months (range 0.1-69.0); 50 developed IA after a median 7.9 months (range 0.1-52.4), 34 within 12 months. The majority (43/50) fulfilled the 2010 American College of Rheumatology/European League Against Rheumatism criteria for rheumatoid arthritis. A model for progression to IA was devised using four variables: tenderness of hand or foot joints, early morning stiffness ≥30 min, high-positive autoantibodies, and positive ultrasonographic power Doppler signal. None of the five individuals at low risk (score 0) progressed to IA, compared with 31% of 29 at moderate risk (1-2) and 62% of 66 at high risk (≥3). Adding shared epitope increased the number at low risk (score 0-1; 0/11 progressed).
In patients presenting with non-specific MSK symptoms and anti-CCP, the risk of progression to IA could be quantified using data available in clinical practice. The proposed risk score may be used to stratify patients for early therapeutic intervention.
NCT02012764 at ClinicalTrials.gov.
We report the observation of radar echoes from the ionization trails of high-energy particle cascades. Data were taken at the SLAC National Accelerator Laboratory, where the full electron beam ...(∼10^{9} e^{-} at ∼10 GeV/e^{-}) was directed into a plastic target to simulate an ultrahigh-energy neutrino interaction. The target was interrogated with radio waves, and coherent radio reflections from the cascades were detected with properties consistent with theoretical expectations. This is the first definitive observation of radar echoes from high-energy particle cascades, which may lead to a viable neutrino detection technology for energies ≳10^{16} eV.
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