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...     

Diffusion-weighted magnetic resonance imaging in rat kidney using two-dimensional navigated,interleaved echo-planar imaging at 7.0 T

The purpose of this study was to investigate the feasibility of two-dimensional (2D) navigated, interleaved multishot echo-planar imaging (EPI) to enhance kidney diffusion-weighted imaging (DWI) in rats at 7.0 T. Fully sampled interleaved four-shot EPI with 2D navigators was tailored for kidney DWI (Sprague–Dawley rats, n = 7) on a 7.0-T small bore preclinical scanner. The image quality of four-shot EPI was compared with T₂-weighted rapid acquisition with relaxation enhancement (RARE) (reference) and single-shot EPI (ss-EPI) without and with parallel imaging (PI). The contrast-to-noise ratio (CNR) was examined to assess the image quality for the EPI approaches. The Dice similarity coefficient and the Hausdorff distance were used for evaluation of image distortion. Mean diffusivity (MD) and fractional anisotropy (FA) were calculated for renal cortex and medulla for all DWI approaches. The corticomedullary difference of MD and FA were assessed by Wilcoxon signed-rank test. Four-shot EPI showed the highest CNR among the three EPI variants and lowest geometric distortion versus T₂-weighted RARE (mean Dice: 0.77 for ss-EPI without PI, 0.88 for ss-EPI with twofold undersampling, and 0.92 for four-shot EPI). The FA map derived from four-shot EPI clearly identified a highly anisotropic region corresponding to the inner stripe of the outer medulla. Four-shot EPI successfully discerned differences in both MD and FA between renal cortex and medulla. In conclusion, 2D navigated, interleaved multishot EPI facilitates high-quality rat kidney DWI with clearly depicted intralayer and interlayer structure and substantially reduced image distortion. This approach enables the anatomic integrity of DWI-MRI in small rodents and has the potential to benefit the characterization of renal microstructure in preclinical studies.     

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...