Efficient polymer nanoparticle-mediated delivery of gene editing reagents into human hematopoietic stem and progenitor cells

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Sports injury prevention programmes from the sports physical therapist's perspective: An international expert Delphi approach

ObjectiveTo provide consensus on how to plan, organize and implement exercise-based injury prevention program (IPP) in sports.DesignDelphi.SettingLimeSurvey platform.ParticipantsExperienced sports physical therapists from the International Federation of Sports Physical Therapy member countries.Main outcome measuresFactors related to sports IPP planning, organization and implementation.ResultsWe included 305 participants from 32 countries. IPP planning should be based on an athlete's injury history, on pre-season screening results, and on injury rates (respectively, 98%, 92%, 89% agreement). In total 97% participants agreed that IPP organization should depend on the athlete's age, 93% on the competition level, and 93% on the availability of low-cost materials. It was agreed that IPP should mainly be implemented in warm-up sessions delivered by the head or strength/conditioning coach, with physical training sessions and individual physical therapy sessions (respectively, 94%, 92%, 90% agreement).ConclusionStrong consensus was reached on (1) IPP based on the athlete's injury history, pre-season screening and evidence-based sports-specific injury rates; (2) IPP organization based on the athlete's age, competition level, and the availability of low-cost materials and (3) IPP implementation focussing on warm-up sessions implemented by the strength/conditioning coach, and/or individual prevention sessions by the physical therapist.     

Emerging innovations in cold plasma therapy against cancer: A paradigm shift

Cancer is one of the major causes of mortality, accounting for ～ 9.5 million deaths globally in 2018. The spectrum of conventional treatment for cancer includes surgery, chemotherapy and radiotherapy. Recently, cold plasma therapy surfaced as a novel technique in the treatment of cancer. The FDA approval of the first trial for the use of cold atmospheric plasma (CAP) in cancer therapy in 2019 is evidence of this. This review highlights the mechanisms of action of CAP. Additionally, its applications in anticancer therapy have been reviewed. In summary, this article will introduce the readers to the exciting field of plasma oncology and help them understand the current status and prospects of plasma oncology.     

Improvement of patient localization repeatability using a light-section based optical surface guidance system in a pre-positioning procedure

PurposeSurface-guided radiotherapy is useful for the pre-positioning and monitoring of radiotherapy. The purpose of this study was to investigate the impact of surface guidance on the repeatability of patient localization and to estimate the specific point at which high positional errors occur.Materials and methodsTen patients without the VOXELAN system (non-VXLN group) and 10 patients with the VOXELAN as the pre-positioning procedure (VXLN group) were included in this analysis. Twelve regions of interest (ROI) were defined in all the patients to verify any misalignment during radiotherapy. Thirteen ROIs were defined on the isocenter.ResultsCompared with the non-VXLN group, the translational positional errors of the VXLN group were the same for all the ROIs. The mean translational positional errors of the VXLN group in the longitudinal direction were approximately 0.1 mm, and the standard deviation was the largest among the three directions in all the ROIs. The magnitude of the standard deviation in the non-VXLN group varied independently of the ROI and direction. The standard deviations of the VXLN group in the longitudinal direction were large in all the ROIs, while the standard deviations in the vertical and lateral directions were small.ConclusionPre-positioning with a surface guidance system reduced the body twist and rotation, which could not be corrected by image-guided radiotherapy alone. Since the VOXELAN can detect positioning errors quickly and without additional radiation exposure to the patient, it can be used as a tool for pre-positioning in radiotherapy.     

子宫浆液性癌的分子学特征及靶向治疗研究进展

子宫浆液性癌（uterine serous carcinoma,USC）是一种特殊类型的子宫内膜癌。有别于常见的子宫内膜样腺癌,USC较为少见,且恶性程度高,侵袭转移风险高,临床上预后较差。随着子宫内膜癌分子学研究的不断深入,分子学特征被应用于子宫内膜癌的病理分型诊断、治疗和预后评价中。研究发现USC中存在多种基因的突变,这些相关基因的突变对该病的诊断和预后具有重要的指导意义。同时,特异性的分子学改变为USC的靶向治疗提供了潜在的治疗靶点。目前,多种靶向治疗手段包括人表皮生长因子受体2（human epidermal growth factor receptor 2,HER2）抑制剂、免疫检查点抑制剂、抗血管生成治疗、磷脂酰肌醇3激酶（phosphoinositide 3-kinases,PI3K）通路抑制剂和多腺苷二磷酸核糖聚合酶[poly(ADP-ribose) polymerase,PARP]抑制剂等被应用于USC的临床治疗研究中,针对性的靶向治疗有望成为USC治疗的新突破。     

Functional estrogen receptor signal transduction pathway activity and antihormonal therapy response in low-grade ovarian carcinoma

Background

Advanced low-grade ovarian carcinoma (LGOC) is difficult to treat. In several studies, high estrogen receptor (ER) protein expression was observed in patients with LGOC, which suggests that antihormonal therapy (AHT) is a treatment option. However, only a subgroup of patients respond to AHT, and this response cannot be adequately predicted by currently used immunohistochemistry (IHC). A possible explanation is that IHC only takes the ligand, but not the activity, of the whole signal transduction pathway (STP) into account. Therefore, in this study, the authors assessed whether functional STP activity can be an alternative tool to predict response to AHT in LGOC.

Methods

Tumor tissue samples were obtained from patients with primary or recurrent LGOC who subsequently received AHT. Histoscores of ER and progesterone receptor (PR) were determined. In addition, STP activity of the ER STP and of six other STPs known to play a role in ovarian cancer was assessed and compared with the STP activity of healthy postmenopausal fallopian tube epithelium.

Results

Patients who had normal ER STP activity had a progression-free survival (PFS) of 16.1 months. This was significantly shorter in patients who had low and very high ER STP activity, with a median PFS of 6.0 and 2.1 months, respectively (p < .001). Unlike ER histoscores, PR histoscores were strongly correlated to the ER STP activity and thus to PFS.

Conclusions

Aberrant low and very high functional ER STP activity and low PR histoscores in patients with LGOC indicate decreased response to AHT. ER IHC is not representative of functional ER STP activity and is not related to PFS.     

Adjunct therapies after botulinum toxin injections in spastic adults: Systematic review and SOFMER recommendations

BackgroundAdjunct therapies (ATs) may further improve outcomes after botulinum toxin injections in spastic patients, but evidence was unclear in previous systematic reviews.ObjectiveTo assess the efficacy of non-pharmacological ATs in spastic adults according to the International Classification of Functioning, Disability and Health and build an expert consensus-based on a Delphi process.MethodsFour electronic databases were searched up to May 2020 for reports of comparative trials of non-pharmacologic ATs after botulinum toxin injections in spastic adults. Then, 25 French experts participated in a two-round Delphi process to build recommendations on the use of ATs.ResultsWe included 32 studies (1202 participants, median 32/study) evaluating the effects of physical agents (n = 9), joint posture procedures (JPPs, n = 11), and active ATs (n = 14), mainly after stroke. The average quality of articles was good for randomised controlled trials (median [interquartile range] PEDro score = 7 [6–8]) but moderate (n = 2) or poor (n = 2) for non-randomised controlled trials (Downs & Black checklist). Meta-analysis was precluded owing to the heterogeneity of ATs, control groups and outcome measures. There is evidence for the use of JPPs except low-dose manual stretching and soft posture techniques. Continuous postures (by taping or casting) are recommended; discontinuous postures (by orthosis) may be preferred in patients with active function. Device-free or device-assisted active ATs may be beneficial in the mid-term (> 3 months after botulinum toxin injections), particularly when performed at a high-intensity (> 3 h/week) as in constraint-induced movement therapy. Self-rehabilitation remains understudied after a focal treatment, but its interest is highlighted by the experts. The use of physical agents is not recommended.ConclusionsJPPs and active ATs (device-assisted or device-free) may further improve impairments and activities after botulinum toxin injections. Further studies are needed to better define the best strategies for ATs as a function of the individual treatment goals, participation and quality of life.Review RegistrationPROSPERO (CRD42018105856).