Bone defect repair is challenging in orthopaedic clinics. For treatment of large bone defects, bone grafting remains the method of choice for the majority of surgeons, as it fills spaces and provides ...support to enhance biological bone repair. As therapeutic agents are desirable for enhancing bone healing, this study was designed to develop such a bioactive composite scaffold (PLGA/TCP/ICT) made of polylactide-co-glycolide (PLGA) and tricalcium phosphate (TCP) as a basic carrier, incorporating a phytomolecule icaritin (ICT), i.e., a novel osteogenic exogenous growth factor. PLGA/TCP/ICT scaffolds were fabricated as PLGA/TCP (control group) and PLGA/TCP in tandem with low/mid/high-dose ICT (LICT/MICT/HICT groups, respectively). To evaluate the in vivo osteogenic and angiogenic potentials of these bioactive scaffolds with slow release of osteogenic ICT, the authors established a 12mm ulnar bone defect model in rabbits. X-ray and high-resolution peripheral quantitative computed tomography results at weeks 2, 4 and 8 post-surgery showed more newly formed bone within bone defects implanted with PLGA/TCP/ICT scaffolds, especially PLGA/TCP/MICT scaffold. Histological results at weeks 4 and 8 also demonstrated more newly mineralized bone in PLGA/TCP/ICT groups, especially in the PLGA/TCP/MICT group, with correspondingly more new vessel ingrowth. These findings may form a good foundation for potential clinical validation of this innovative bioactive scaffold incorporated with the proper amount of osteopromotive phytomolecule ICT as a ready product for clinical applications.
This study evaluated maintenance treatment with niraparib, a potent inhibitor of poly(ADP-ribose) polymerase 1/2, in patients with platinum-sensitive recurrent ovarian cancer.
In this phase III, ...double-blind, placebo-controlled study conducted at 30 centers in China, adults with platinum-sensitive recurrent ovarian cancer who had responded to their most recent platinum-containing chemotherapy were randomized 2 : 1 to receive oral niraparib (300 mg/day) or matched placebo until disease progression or unacceptable toxicity (NCT03705156). Following a protocol amendment, patients with a bodyweight <77 kg or a platelet count <150 × 103/μl received 200 mg/day, and all other patients 300 mg/day, as an individualized starting dose (ISD). Randomization was carried out by an interactive web response system and stratified by BRCA mutation, time to recurrence following penultimate chemotherapy, and response to most recent chemotherapy. The primary endpoint was progression-free survival (PFS) assessed by blinded independent central review.
Between 26 September 2017 and 2 February 2019, 265 patients were randomized to receive niraparib (n = 177) or placebo (n = 88); 249 patients received an ISD (300 mg, n = 14; 200 mg, n = 235) as per protocol. In the intention-to-treat population, median PFS was significantly longer for patients receiving niraparib versus placebo: 18.3 95% confidence interval (CI), 10.9-not evaluable versus 5.4 (95% CI, 3.7-5.7) months hazard ratio (HR) = 0.32; 95% CI, 0.23-0.45; P < 0.0001, and a similar PFS benefit was observed in patients receiving an ISD, regardless of BRCA mutation status. Grade ≥3 treatment-emergent adverse events occurred in 50.8% and 19.3% of patients who received niraparib and placebo, respectively; the most common events were neutrophil count decreased (20.3% versus 8.0%) and anemia (14.7% versus 2.3%).
Niraparib maintenance treatment reduced the risk of disease progression or death by 68% and prolonged PFS compared to placebo in patients with platinum-sensitive recurrent ovarian cancer. Individualized niraparib dosing is effective and safe and should be considered standard practice in this setting.
•Chinese patients with platinum-sensitive recurrent ovarian cancer received maintenance niraparib (n = 177) or placebo (n = 88).•Median PFS was longer for niraparib versus placebo: 18.3 versus 5.4 months (HR = 0.32; 95% CI, 0.23-0.45; P < 0.0001).•Niraparib had a similar PFS benefit for 249 patients receiving individualized dosing based on bodyweight and platelet count.•Grade ≥3 treatment-emergent adverse events occurred in 50.8% and 19.3% of patients who received niraparib and placebo, respectively.•In the niraparib group, Grade ≥3 platelet count decreased/thrombocytopenia occurred in 11.3% of patients.
Background
Diet and exercise during pregnancy have been used to prevent gestational diabetes mellitus (GDM) with some success.
Objective
To examine the effectiveness of lifestyle intervention on GDM ...prevention and to identify key effectiveness moderators to improve the prevention strategy.
Search strategy
Pubmed, Scopus, Cochrane, and cross‐references were searched.
Selection criteria
Randomised controlled trials (RCTs) evaluating lifestyle interventions during pregnancy for GDM prevention.
Data collection and analysis
Two independent reviewers extracted data. A random‐effects model was used to analyse the relative risk (RR) and 95% confidence interval (95% CI). Meta‐regressions and subgroup analyses were used to investigate important moderators of effectiveness.
Main results
Forty‐seven RCTs involving 15 745 participants showed that diet and exercise during pregnancy were preventive of GDM (RR 0.77, 95% CI 0.69–0.87). Four key aspects were identified to improve the preventive effect: targeting the high‐risk population; an early initiation of the intervention; the correct intensity and frequency of exercise; and gestational weight gain management. Although 24 RCTs targeted women who were overweight or obese, body mass index (BMI) failed to predict the effectiveness of an intervention. Instead, interventions are most effective in high‐incidence populations rather than simply in women who are overweight or obese. Furthermore, exercise of moderate intensity for 50–60 minutes twice a week could lead to an approximately 24% reduction in GDM.
Conclusion
The best strategy to prevent GDM is to target the high‐risk population predicted by risk evaluation models and to control the gestational weight gain of women through intensified diet and exercise modifications early in their pregnancy.
Tweetable
Four key effectiveness moderators of lifestyle interventions for GDM prevention.
Tweetable
Four key effectiveness moderators of lifestyle interventions for GDM prevention.
Abstract
Understanding the competition between superconductivity and other ordered states (such as antiferromagnetic or charge-density-wave (CDW) state) is a central issue in condensed matter ...physics. The recently discovered layered kagome metal
A
V
3
Sb
5
(
A
= K, Rb, and Cs) provides us a new playground to study the interplay of superconductivity and CDW state by involving nontrivial topology of band structures. Here, we conduct high-pressure electrical transport and magnetic susceptibility measurements to study CsV
3
Sb
5
with the highest
T
c
of 2.7 K in
A
V
3
Sb
5
family. While the CDW transition is monotonically suppressed by pressure, superconductivity is enhanced with increasing pressure up to P1 ≈ 0.7 GPa, then an unexpected suppression on superconductivity happens until pressure around 1.1 GPa, after that,
T
c
is enhanced with increasing pressure again. The CDW is completely suppressed at a critical pressure P2 ≈ 2 GPa together with a maximum
T
c
of about 8 K. In contrast to a common dome-like behavior, the pressure-dependent
T
c
shows an unexpected double-peak behavior. The unusual suppression of
T
c
at P1 is concomitant with the rapidly damping of quantum oscillations, sudden enhancement of the residual resistivity and rapid decrease of magnetoresistance. Our discoveries indicate an unusual competition between superconductivity and CDW state in pressurized kagome lattice.
To evaluate the effect of the different doses of antithymocyte globulin (ATG) on the incidence of acute GVHD among patients receiving hematopoietic SCT without ex vivo T-cell-depletion from ...haploidentical donors, 224 patients with standard-risk hematological malignancy were randomized in this study. One hundred and twelve patients received 6 mg/kg ATG, whereas the remaining patients received 10 mg/kg ATG. This study was registered at http://www.chictr.org as No. ChiCTR-TRC-11001761. The incidence of grade III-IV acute GVHD was higher in the ATG-6 group (16.1%, 95% confidence interval (CI), 9.1-23.1%) than in the ATG-10 group (4.5%, CI, 0.7-8.3%, P=0.005, 95% CI for the difference, -19.4% to -3.8%). EBV reactivation occurred more frequently in the ATG-10 group (25.3%, 17.1-33.5%) than in the ATG-6 group (9.6% (4.0-15.2%), P=0.001). The 1-year disease-free survival rates were 84.3% (77.3-91.3%) and 86.0% (79.2-92.8%) for the ATG-6 group and ATG-10 groups, respectively (P=0.88). In conclusion, although 6 mg/kg ATG applied in haploidentical transplantation decreased the risk of EBV reactivation compared with 10 mg/kg ATG, this treatment exposes patients to a higher risk for severe acute GVHD.
Our understanding of when and how humans adapted to living on the Tibetan Plateau at altitudes above 2000 to 3000 meters has been constrained by a paucity of archaeological data. Here we report data ...sets from the northeastern Tibetan Plateau indicating that the first villages were established only by 5200 calendar years before the present (cal yr B.P.). Using these data, we tested the hypothesis that a novel agropastoral economy facilitated year-round living at higher altitudes since 3600 cal yr B.P. This successful subsistence strategy facilitated the adaptation of farmers-herders to the challenges of global temperature decline during the late Holocene.
Summary
Background
Magnetic resonance enterography (MRE) has been proposed as a non‐ionising alternative method to computed tomography enterography (CTE). Some studies have directly compared CTE and ...MRE in patients with small bowel Crohn's disease (CD) with variable results.
Aim
To compare the overall diagnostic accuracy in assessing the activity of small bowel and complications.
Methods
MEDLINE, EMBASE and Cochrane databases were searched for studies on the accuracy of MRE and CTE, as compared with a pre‐defined reference standard. Pooled sensitivity, specificity, the weighted area under the curve (AUC), incremental yield (IY) and other diagnostic indices were evaluated.
Results
A total of 290 CD patients from six different studies were analysed. The pooled sensitivity and specificity for MRE in detecting active small bowel CD was 87.9% 95% confidence interval (CI), 81.8–92.5 and 81.2% (95% CI: 71.9–88.4) respectively. The AUC under the summary receiver‐operating characteristic (sROC) of MRE was 0.905 (SEM 0.03, standard error of the mean). Likewise, the pooled sensitivity and specificity of CTE in detecting active small bowel CD was 85.8% (95% CI: 79.2–90.9) and 83.6% (95% CI: 75.3–90.1) with the AUC of 0.898. The AUC of MRE in detecting fistula, stenosis and abscess was 0.936, 0.931 and 0.996, respectively, compared to 0.963, 0.616 and 0.899 of CTE. No statistically significant IY for MRE vs. CTE was found (fixed model, P > 0.05).
Conclusions
Magnetic resonance enterography has a diagnostic effectiveness comparable to computed tomography enterography, thus may serve as a radiation‐free alternative for evaluation of patients with Crohn's disease.
Metal and its oxide nanoparticles show ideal pharmacological activity, especially in anti-tumor therapy. Our previous study demonstrated that cuprous oxide nanoparticles (CONPs) selectively induce ...apoptosis of tumor cells in vitro. To explore the anti-tumor properties of CONPs in vivo, we used the particles to treat mouse subcutaneous melanoma and metastatic lung tumors, based on B16-F10 mouse melanoma cells, by intratumoral and systemic injections, respectively. The results showed that CONPs significantly reduced the growth of melanoma, inhibited the metastasis of B16-F10 cells and increased the survival rate of tumor-bearing mice. Importantly, the results also indicated that CONPs were rapidly cleared from the organs and that these particles exhibited little systemic toxicity. Furthermore, we observed that CONPs targeted the mitochondria, which resulted in the release of cytochrome C from the mitochondria and the activation of caspase-3 and caspase-9 after the CONPs entered the cells. In conclusion, CONPs can induce the apoptosis of cancer cells through a mitochondrion-mediated apoptosis pathway, which raises the possibility that CONPs could be used to cure melanoma and other cancers.
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