Personal comorbidities and their subsequent risks for liver,gallbladder and bile duct cancers

Many environmental risk factors for hepatobiliary cancers are known but whether they are associated with specific cancer types is unclear. We present here a novel approach of assessing standardized incidence ratios (SIRs) of previously diagnosed comorbidities for hepatocellular carcinoma (HCC), gallbladder cancer (GBC), cholangiocarcinoma (CCA) and ampullary cancer. The 13 comorbidities included alcohol and nonalcohol related liver disease, chronic obstructive pulmonary disease, gallstone disease, viral and other kinds of hepatitis, infection of bile ducts, hepatic and other autoimmune diseases, obesity and diabetes. Patients were identified from the Swedish Inpatient Register from 1987 to 2018, and their cancers were followed from 1997 onwards. SIRs for HCC were 80 to 100 in men and women diagnosed with hepatitis C virus and they were also >10 in patients diagnosed with hepatitis B virus, other kind of hepatitis, hepatic autoimmune disease and nonalcohol related liver disease. Many of these risks, as well as alcohol related liver disease, were either specific to HCC or were shared with intrahepatic CCA. For GBC, CCA and ampullary cancer infection of bile ducts was the main risk factor. Gallstone disease, nonhepatic autoimmune diseases and diabetes were associated with all hepatobiliary cancers. The limitations of the study include inability to cover some rare risk factors and limited follow-up time. Many of the considered comorbidities are characterized by chronic inflammation and/or overt immune disturbance in autoimmune diseases. The results suggest that local chronic inflammation and a related immune disturbance is the carcinogenic trigger for all these cancers.     

Principles of environmentally-sustainable anaesthesia: a global consensus statement from the World Federation of Societies of Anaesthesiologists

The Earth’s mean surface temperature is already approximately 1.1°C higher than pre-industrial levels. Exceeding a mean 1.5°C rise by 2050 will make global adaptation to the consequences of climate change less possible. To protect public health, anaesthesia providers need to reduce the contribution their practice makes to global warming. We convened a Working Group of 45 anaesthesia providers with a recognised interest in sustainability, and used a three-stage modified Delphi consensus process to agree on principles of environmentally sustainable anaesthesia that are achievable worldwide. The Working Group agreed on the following three important underlying statements: patient safety should not be compromised by sustainable anaesthetic practices; high-, middle- and low-income countries should support each other appropriately in delivering sustainable healthcare (including anaesthesia); and healthcare systems should be mandated to reduce their contribution to global warming. We set out seven fundamental principles to guide anaesthesia providers in the move to environmentally sustainable practice, including: choice of medications and equipment; minimising waste and overuse of resources; and addressing environmental sustainability in anaesthetists’ education, research, quality improvement and local healthcare leadership activities. These changes are achievable with minimal material resource and financial investment, and should undergo re-evaluation and updates as better evidence is published. This paper discusses each principle individually, and directs readers towards further important references.     

Mesenchymal neoplasms with NTRK and other kinase gene alterations

Kinase alterations are increasingly recognised as oncogenic drivers in mesenchymal tumours. Infantile fibrosarcoma and the related renal tumour, congenital mesoblastic nephroma, were among the first solid tumours shown to harbour recurrent tyrosine kinase fusions, with the canonical ETV6::NTRK3 fusion identified more than 20 years ago. Although targeted testing has long been used in diagnosis, the advent of more robust sequencing techniques has driven the discovery of kinase alterations in an array of mesenchymal tumours. As our ability to identify these genetic alterations has improved, as has our recognition and understanding of the tumours that harbour these alterations. Specifically, this study will focus upon mesenchymal tumours harbouring NTRK or other kinase alterations, including tumours with an infantile fibrosarcoma-like appearance, spindle cell tumours resembling lipofibromatosis or peripheral nerve sheath tumours and those occurring in adults with a fibrosarcoma-like appearance. As publications describing the histology of these tumours increase so, too, do the variety kinase alterations reported, now including NTRK1/2/3, RET, MET, RAF1, BRAF, ALK, EGFR and ABL1 fusions or alterations. To date, these tumours appear locally aggressive and rarely metastatic, without a clear link between traditional features used in histological grading (e.g. mitotic activity, necrosis) and outcome. However, most of these tumours are amenable to new targeted therapies, making their recognition of both diagnostic and therapeutic import. The goal of this study is to review the clinicopathological features of tumours with NTRK and other tyrosine kinase alterations, discuss the most common differential diagnoses and provide recommendations for molecular confirmation with associated treatment implications.     

Association of TPH1 and TPH2 Gene Polymorphisms with the Risk of Developing Psychoneurological Disorders

Neuroscience and Behavioral Physiology - The question of the involvement of impairments to the metabolism of melatonin and its precursors (tryptophan and serotonin) in the development of...     

重组人表皮生长因子凝胶联合CO2点阵激光治疗增生性瘢痕的效果观察

目的观察重组人表皮生长因子凝胶联合CO₂点阵激光治疗烧伤及创伤后增生性瘢痕的临床效果。 方法选择2020年12月至2021年10月安徽医科大学第一附属医院烧伤与创面修复外科收治的20例增生性瘢痕患者，按照随机数字表法将患者分为联合治疗组及单纯激光治疗组，每组10例。术前均对2组患者术区进行拍照存像、消毒、擦干，局部均匀涂抹5%复方利多卡因乳膏后以无菌薄膜封闭保护60 min，擦去乳膏后再次消毒术区。术中使用CO₂点阵激光治疗仪对患者瘢痕部位进行扫描，根据患者增生性瘢痕厚度选定合适的机器参数，维持机器频率300 Hz及密度5%，在20～30 J调整能量参数的大小，时间间隔1 s，保证点阵矩形完全覆盖增生瘢痕，允许2次激光形成的热损伤矩阵之间存在25%面积的重叠。术后即刻冷敷创面60 min，冷敷结束至术后1周，单纯激光治疗组不外用任何药物，联合治疗组术区加用重组人表皮生长因子凝胶外用，3次/d。术后3 d治疗部位不碰水，若出现感染情况，可以加用抗生素软膏，点状损伤创面外痂皮未掉落完全时禁止擦洗创面，禁止直接剥除痂皮，禁止术区涂抹化妆品等，避免接受阳光直射。于第1次激光治疗后2个月进行第2次激光治疗，以2次CO₂点阵激光治疗为1个疗程，1个疗程治疗后间隔2个月待术区稳定后行疗效判断，计算2组患者治疗的总有效率；根据温哥华瘢痕量表(VSS)与患者与观察者瘢痕评估量表(POSAS)对患者治疗前、第1次激光治疗后2个月、第2次激光治疗后2个月瘢痕的各项指标进行评分。数据比较采用重复测量方差分析和χ²检验。 结果(1)治疗1个疗程后2个月，单纯激光治疗组与联合治疗组患者治疗的总有效率分别为80%(8/10)、90%(9/10)，2组间比较差异无统计学意义(χ²＝2.40，P＝0.49)。(2)对2组VSS评分的各项指标进行比较，其中疼痛、瘙痒、柔软度及厚度评分的组内及组间各时相点比较，差异均无统计学意义(P>0.05)。治疗前、第1次激光治疗后2个月及第2次激光治疗后2个月，单纯激光治疗组VSS评分中色泽评分分别为(1.9±0.7)、(1.9±0.1)、(1.8±1.0)分，联合治疗组分别为(2.9±0.7)、(2.8±0.6)、(1.9±0.7)分，2组在不同时相点组内比较，差异有统计学意义(F＝ 26.143，P<0.05)；2组组间不同时相点比较，差异有统计学意义(F＝6.753，P＝0.018)。治疗前、第1次激光治疗后2个月及第2次激光治疗后2个月，单纯激光治疗组VSS评分中血管分布评分分别为(1.8±1.0)、(1.7±0.7)、(1.5±1.0)分，联合治疗组分别为(2.6±0.5)、(2.5±0.5)、(1.7±0.8)分，2组在不同时相点组内比较，差异有统计学意义(F＝17.603，P<0.05)，2组组间不同时相点比较，差异无统计学意义(F＝ 2.538，P＝0.129)。(3)对2组POSAS评分的各项指标进行比较，其中厚度、粗糙度、柔软度和表面积评分的组内及组间各时相点比较，差异均无统计学意义(P>0.05)。治疗前、第1次激光治疗后2个月及第2次激光治疗后2个月，单纯激光治疗组POSAS评分中色泽评分分别为(4.9±2.6)、(4.1±0.8)、(3.5±2.0)分，联合治疗组分别为(7.6±1.1)、(6.8±1.4)、(5.4±1.8)分，2组在不同时相点组内比较，差异有统计学意义(F＝ 26.509，P<0.05)，2组组间不同时相点比较，差异有统计学意义(F＝ 8.973，P＝0.008)。治疗前、第1次激光治疗后2个月及第2次激光治疗后2个月，单纯激光治疗组POSAS评分中血管分布评分分别为(4.4±2.1)、(3.9±0.9)、(3.5±1.6)分，联合治疗组分别为(6.3±1.1)、(5.7±2.0)、(4.5±1.6)分，2组在不同时相点组内比较，差异有统计学意义(F＝ 20.118，P<0.05)，2组组间不同时相点比较，差异有统计学意义(F＝ 5.744，P＝0.028)。 结论重组人表皮生长因子凝胶联合CO₂点阵激光及单独使用CO₂点阵激光治疗增生性瘢痕均效果明确，但联合使用重组人表皮生长因子凝胶能有效促进创面愈合、改善瘢痕组织血管分布和减少局部色素沉着。     

Day-level associations of physical activity and sedentary time in mother–child dyads across three years: a multi-wave longitudinal study using accelerometers

Journal of Behavioral Medicine - Understanding associations between mothers’ and children’s physical activity and sedentary behavior on more fine-grained timescales can provide insights...     

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.     

High Order Finite Difference Hermite WENO Fixed-Point Fast Sweeping Method for Static Hamilton-Jacobi Equations

In this paper, we combine the nonlinear HWENO reconstruction in [43] and the fixed-point iteration with Gauss-Seidel fast sweeping strategy, to solve the static Hamilton-Jacobi equations in a novel HWENO framework recently developed in [22]. The proposed HWENO frameworks enjoys several advantages. First, compared with the traditional HWENO framework, the proposed methods do not need to introduce additional auxiliary equations to update the derivatives of the unknown function $\phi$. They are now computed from the current value of $\phi$ and the previous spatial derivatives of $\phi$. This approach saves the computational storage and CPU time, which greatly improves the computational efficiency of the traditional HWENO scheme. In addition, compared with the traditional WENO method, reconstruction stencil of the HWENO methods becomes more compact, their boundary treatment is simpler, and the numerical errors are smaller on the same mesh. Second, the fixed-point fast sweeping method is used to update the numerical approximation. It is an explicit method and does not involve the inverse operation of nonlinear Hamiltonian, therefore any Hamilton-Jacobi equations with complex Hamiltonian can be solved easily. It also resolves some known issues, including that the iterative number is very sensitive to the parameter $ε$ used in the nonlinear weights, as observed in previous studies. Finally, to further reduce the computational cost, a hybrid strategy is also presented. Extensive numerical experiments are performed on two-dimensional problems, which demonstrate the good performance of the proposed fixed-point fast sweeping HWENO methods.     

Correction to: The protean world of non-coding RNAs in glioblastoma

Journal of Molecular Medicine -