Top advances of the year: Precision oncology

The advent of precision medicine has changed the landscape of oncologic biomarkers, drug discovery, drug development, and, more importantly, outcomes for patients with cancer. Precision oncology entails the genomic profiling of tumors to detect actionable aberrations. The advances in clinical next-generation sequencing from both tumor tissue and liquid biopsy and availability of targeted therapies has rapidly entered mainstream clinical practice. In this review, recent major developments in precision oncology that have affected outcomes for patients with cancer are discussed. Rapid clinical development was seen of targeted agents across various mutational profiles such as KRASG12C (which was considered “undruggable” for almost 4 decades), Exon 20 insertions, and RET mutations. Approaches to precision chemotherapy delivery by the introduction of antibody drug conjugates in the armamentarium against lung cancer has been appreciated.     

Understanding How Newly Implemented Rehabilitation Best Practices Are Sustained: A Realist Review

ObjectiveWe conducted a realist review to understand how (mechanism) and in what circumstances (context) evidence-based practices are sustained in rehabilitation (outcome).Data SourcesMEDLINE, Embase, reference lists, and targeted websites.Study SelectionTwo independent reviewers calibrated study selection; then 1 reviewer screened all titles and abstracts, while the second reviewer screened a random 20%. We repeated this process for full texts. We included 115 documents representing 61 implementation projects (8.9% of identified documents). Included documents described implementation projects in which physical therapists, occupational therapists, and/or speech-language pathologists were the target users of an evidence-based practice.Data ExtractionTwo reviewers repeated the independent process described in study selection to extract basic study and sustainability characteristics as well as context, mechanism, outcome, and strategy text.Data SynthesisUsing basic numerical analyses, we found that only 54% of evidence-based practices in rehabilitation are sustained. Furthermore, while authors who reported sustainability planning sustained the practice 94% of the time, sustainability planning in rehabilitation is rare (only reported 26% of the time). Extracted text was synthesized using the realist technique of inductive and deductive retroduction in which context, mechanism, outcome, and strategy text are combined into narrative explanations of how sustainability works. To inform these explanations, we applied normalization process theory and the theory of planned behavior. Collectively, the 52 identified narratives provide evidence for 3 patterns: (1) implementation and sustainability phases are interconnected, (2) continued use of the evidence-based practice can be interpreted as the ultimate sustainability outcome, and (3) intermediate sustainability outcomes (ie, fit/alignment, financial support, benefits, expertise) can become contextual features influencing other sustainability outcomes.ConclusionsImplementation teams can use the narrative explanations generated in this review to optimize sustainability planning. This can sustain practice changes and improve quality of care and patient outcomes. Future research should seek to iteratively refine the proposed narrative explanations.     

沙盘游戏疗法在肿瘤放疗患者中的应用

目的探讨沙盘游戏疗法对肿瘤放疗患者心理痛苦及生活质量的作用。方法采用便利抽样法,选取2019年1—12月于上海市质子重离子医院住院进行放疗的49例肿瘤患者为研究对象,采用分层随机分组方法,将患者随机分为对照组28例和试验组21例。对照组给予常规心理护理,试验组在此基础上给予沙盘游戏疗法。采用心理痛苦温度计和欧洲癌症研究与治疗组织生命质量核心量表中的5个功能维度比较两组患者干预前后的心理痛苦程度和生活质量水平。结果干预后,两组患者心理痛苦温度计得分均低于干预前,且试验组得分低于对照组,差异有统计学意义(P<0.01)。干预前后试验组患者的躯体功能、角色功能、认知功能、情绪功能、社会功能维度得分下降程度均小于对照组,差异有统计学意义(P<0.01)。结论沙盘游戏疗法对肿瘤放疗患者的心理痛苦和生活质量有一定改善作用。     

A comparison of efficacy and safety of complementary and alternative therapies for severe mycoplasma pneumonia in children: A protocol for systematic review and meta-analysis

Background:In recent years, the incidence rate of children with severe Mycoplasma pneumoniae pneumonia (SMPP) is increasing, which poses a great threat to children''s life and safety. There are some limitations in the existing drugs for the treatment of SMPP, and the supplementary and alternative therapy of SMPP plays an irreplaceable role in the treatment of this disease. This study will evaluate the efficacy and safety of various complementary and alternative therapies for SMPP by means of mesh meta-analysis. In order to provide the basis for clinical rational use.Methods:Two researchers will independently and comprehensively searched the Cochrane Central controlled trials registry, Cochrane Library, PubMed, web of science, EMBASE, CNKI, and Wanfang database to collect randomized controlled trials (RCT) studies on complementary and alternative therapies for SMPP. And the relevant references included in the systematic review/meta-analysis are screened. The retrieval time limit is from the establishment of the database to November 2020. We will use Revman 5.3 software for meta-analysis and use grade to grade the quality of evidence in the net meta-analysis (NMA).Results:The aim of this study was to compare the efficacy and safety of different complementary and alternative therapies in the treatment of SMPP, with a view to evaluating and ranking different interventions.Conclusion:The supplement and replacement therapy of SMPP can improve the clinical efficacy, relieve the clinical symptoms, improve the quality of life of children, and reduce adverse reactions, which can provide strong support for the rational use of clinicians.INPLASY registration number:INPLASY2020110079.     

An update in pathologic diagnosis of uterine mesenchymal tumours

Recent discovery of new disease-defining molecular alterations and development of novel targeted therapies has dramatically changed the classification and management of uterine mesenchymal neoplasms. This review discusses diagnostic updates in endometrial stromal sarcoma, PEComa, uterine tumor resembling ovarian sex cord tumor (UTROSCT), inflammatory myofibroblastic tumor, NTRK fusion uterine sarcoma, COL1A1-PDGFB fusion sarcoma, and SMARC-deficient uterine sarcoma. Key clinical, morphologic, immunophenotypic, and molecular features are reviewed, with emphasis on common differential diagnoses and pitfalls, and their impact on prognosis or management. Where applicable, the role of novel targeted therapies is discussed. A stepwise approach to uterine mesenchymal neoplasms can achieve a proper diagnosis and guide appropriate clinical management in most cases. Nonetheless, given the rarity of these tumors, their overlapping pathologic features, and rapid evolution in their classification and management, we advocate a low threshold for diagnostic consultation.     

Update on adrenal cortical neoplasia

The adrenal cortex gives rise to a biologically heterogenous group of neoplasms, each with a distinct morphology, antigen expression and molecular profile. Adrenal cortical adenomas have excellent prognosis and are usually cured by surgical resection alone, while adrenal cortical carcinomas are very aggressive tumors with a poor prognosis regardless of therapy. These tumors are rare and often challenging for a pathologist to diagnose, as significant overlap exists between benign and malignant lesions in some cases. In this review, we attempt to summarize most important histologic and clinical features of adrenal cortical adenomas and carcinomas, clarify the use of different grading systems, the use of special stains and the differential diagnosis for practicing pathologists. Most relevant hereditary syndromes associated with adrenal cortical tumors are listed. Updates in molecular alterations in adrenal cortical neoplasms and hyperplastic diseases as well as their clinical significance and potential therapeutic implications are also discussed.     

Interactions between human microbiome,liver diseases,and immunosuppression after liver transplant

In liver transplant patients, solid tumors and post-transplant lymphoproliferative disorders have emerged as significant long-term mortality causes. In addition, it is assumed that de novo malignancy after liver transplantation (LT) is the second-leading cause of death after cardiovascular complications. Well-established risk factors for post-transplant lymphoproliferative disorders and solid tumors are calcineurin inhibitors, tacrolimus, and cyclosporine, the cornerstones of all immunosuppressive therapies used after LT. The loss of immunocompetence facilitated by the host immune system due to prolonged immunosuppressive therapy leads to cancer development, including LT patients. Furthermore, various mechanisms such as bacterial dysbiosis, activation through microbe-associated molecular patterns, leaky gut, and bacterial metabolites can drive cancer-promoting liver inflammation, fibrosis, and genotoxicity. Therefore, changes in human microbiota composition may contribute further to de novo carcinogenesis associated with the severe immunosuppression after LT.