CAR and CSTR Cardiac Computed Tomography (CT) Practice Guidelines: Part 2-Non-Coronary Imaging.

The cardiac computed tomography (CT) practice guidelines provide an updated review of the technological improvements since the publication of the first Canadian Association of Radiologists (CAR) cardiac CT practice guidelines in 2009. An overview of the current evidence supporting the use of cardiac CT in the most common clinical scenarios, standards of practice to optimize patient preparation and safety as well as image quality are described. Coronary CT angiography (CCTA) is the focus of Part I. In Part II, an overview of cardiac CT for non-coronary indications that include valvular and pericardial imaging, tumour and mass evaluation, pulmonary vein imaging, and imaging of congenital heart disease for diagnosis and treatment monitoring are discussed. The guidelines are intended to be relevant for community hospitals and large academic centres with established cardiac CT imaging programs.

Guideline No. 425a: Cannabis Use Throughout Women's Lifespans - Part 1: Fertility, Contraception, Menopause, and Pelvic Pain.

OBJECTIVE: To provide health care providers with the best evidence on cannabis use with respect to women's health. Areas of focus include general patterns of cannabis use as well as safety of use; care for women who use cannabis; stigma; screening, brief intervention, and referral to treatment; impact on hormonal regulation; reproductive health, including contraception and fertility; sexual function; effects on perimenopausal and menopausal symptoms; and use in chronic pelvic pain syndromes. TARGET POPULATION: The target population includes all women currently using or contemplating using cannabis. OUTCOMES: Open, evidence-informed dialogue about cannabis use, which will lead to improvement in patient care. BENEFITS, HARMS, AND COSTS: Exploring cannabis use through a trauma-informed approach provides the health care provider and patient with an opportunity to build a strong, collaborative, therapeutic alliance. This alliance empowers women to make informed choices about their own care. It also allows for the diagnosis and possible treatment of cannabis use disorders. Use should not be stigmatized, as stigma leads to poor "partnered care" (i.e., the partnership between the patient and care provider). Multiple side effects of cannabis use may be mistaken for other disorders. Currently, use of cannabis to treat women's health issues is not covered by public funding; as a result, individual users must pay the direct cost. The indirect costs of cannabis use are unknown. Thus, health care providers and patients must understand the role of cannabis in women's health issues, so that women can make knowledgeable decisions. EVIDENCE: PubMed, EMBASE, and grey literature were searched to identify studies of "cannabis use and effect on infertility, contraception, perimenopause and menopausal symptoms, and pelvic pain" published between January 1, 2018 and February 18, 2021. All clinical trials, observational studies, reviews (including systematic reviews and meta-analyses), guidelines, and conference consensus statements were included. Publications were screened for relevance. The search terms were developed using the Medical Subject Headings (MeSH) terms and keywords (and variants), including cannabis, cannabinoids, marijuana, dexanabinol, dronabinol, tetrahydrocannabinol; the specific terms to capture women's health were estrogen, estradiol, medroxyprogesterone acetate, vaginal contraception, oral contraceptives, fertilization, amenorrhea, oligomenorrhea, pelvic pain, dysmenorrhea, endometriosis, interstitial cystitis, vulvodynia, and menopause. VALIDATION METHODS: The authors rated the quality of evidence and strength of recommendations using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. See online Appendix A (Tables A1 for definitions and A2 for interpretations of strong and weak recommendations). INTENDED AUDIENCE: All heath care providers who care for women. SUMMARY STATEMENTS: RECOMMENDATIONS.

Directive clinique no 425a : Le cannabis aux différentes périodes de la vie des femmes - Partie 1 : Fertilité, contraception, ménopause et douleur pelvienne.

OBJECTIF: Fournir aux fournisseurs de soins de santé les meilleures données probantes sur l'utilisation de cannabis et la santé des femmes. Les domaines d'intérêt sont : les profils généraux d'utilisation du cannabis ainsi que la sécurité de la consommation; les soins aux femmes qui utilisent le cannabis; la stigmatisation; le dépistage, l'intervention brève et l'orientation vers le traitement; les effets sur la régulation hormonale; la santé reproductive, y compris la contraception et la fertilité; la fonction sexuelle; les effets sur les symptômes périménopausiques et postménopausiques; et l'utilisation dans le traitement des syndromes de douleur pelvienne chronique. POPULATION CIBLE: La population cible comprend toutes les femmes qui consomment ou utilisent du cannabis ou qui envisagent de le faire. RéSULTATS: Un dialogue ouvert et fondé sur des données probantes relativement à l'utilisation et la consommation de cannabis, dialogue qui mènera à l'amélioration des soins aux patientes. BéNéFICES, RISQUES ET COûTS: L'exploration de l'utilisation et de la consommation de cannabis par une approche basée sur la connaissance des traumatismes donne l'occasion au fournisseur de soins et à la patiente de créer une solide alliance thérapeutique collaborative. Cette alliance permet aux femmes de faire des choix éclairés sur leurs propres soins. Elle facilite également le diagnostic et le traitement possible des troubles de l'usage du cannabis. Il ne faut pas stigmatiser la consommation, car la stigmatisation nuit à l'alliance thérapeutique (c'est-à-dire le partenariat entre la patiente et le fournisseur de soins). Plusieurs effets indésirables de la consommation de cannabis peuvent être confondus avec d'autres problèmes de santé. À l'heure actuelle, l'utilisation du cannabis pour traiter les problèmes de santé féminine n'est pas financée par le secteur public; par conséquent, les utilisatrices doivent assumer les coûts directs. Les coûts indirects de l'utilisation de cannabis sont inconnus. Ainsi, les fournisseurs de soins et les patientes doivent comprendre le rôle du cannabis dans les problèmes de santé féminine de sorte que les femmes puissent prendre des décisions éclairées. DONNéES PROBANTES: Des recherches ont été effectuées dans PubMed, Embase et la littérature grise pour recenser des études publiées entre le 1er janvier 2018 et le 18 février 2021 concernant l'utilisation du cannabis et ses effets sur l'infertilité, la contraception, les symptômes périménopausiques et postménopausiques et la douleur pelvienne. Toutes les publications des types suivants ont été incluses : essais cliniques, études observationnelles, revues (y compris les revues systématiques et les méta-analyses), directives cliniques et déclarations de conférences de consensus. Un survol des publications a été effectué pour en confirmer la pertinence. Les termes de recherche ont été définis à l'aide des termes MeSH (Medical Subject Headings) et mots clés (et variantes) suivants : cannabis, cannabinoids, marijuana, dexanabinol, dronabinol et tetrahydrocannabinol. À ces termes ont été combinés les termes suivants afin de cerner la santé des femmes : estrogen, estradiol, medroxyprogesterone acetate, vaginal contraception, oral contraceptives, fertilization, amenorrhea, oligomenorrhea, pelvic pain, dysmenorrhea, endometriosis, interstitial cystitis, vulvodynia et menopause. MéTHODES DE VALIDATION: Les auteurs ont évalué la qualité des données probantes et la force des recommandations en utilisant l'approche d'évaluation, de développement et d'évaluation (GRADE). Voir l'annexe A en ligne (tableau A1 pour les définitions et tableau A2 pour l'interprétation des recommandations fortes et faibles). PROFESSIONNELS CONCERNéS: Tous les fournisseurs de soins de santé qui prodiguent des soins aux femmes. DÉCLARATIONS SOMMAIRES: RECOMMANDATIONS.

Guideline No. 425b: Cannabis Use Throughout Women's Lifespans - Part 2: Pregnancy, the Postnatal Period, and Breastfeeding.

OBJECTIVE: To provide health care providers with the best evidence on cannabis use and women's health. Areas of focus include screening, dependence, and withdrawal; communication and documentation; pregnancy (including maternal and fetal outcomes); maternal pain control; postpartum care (including second-hand smoking and parenting); and breastfeeding. TARGET POPULATION: The target population includes women who are planning a pregnancy, pregnant, or breastfeeding. BENEFITS, HARMS, AND COSTS: Discussing cannabis use with women who are planning a pregnancy, pregnant, or breastfeeding allows them to make informed choices about their cannabis use. Based on the limited evidence, cannabis use in pregnancy or while breastfeeding should be avoided, or reduced as much as possible if abstaining is not feasible, given the absence of safety and long-term follow up data on cannabis-exposed pregnancies and infants. EVIDENCE: PubMed and Cochrane Library databases were searched for articles relevant to cannabis use during pregnancy and breastfeeding published between January 1, 2018, and February 5, 2021. The search terms were developed using the MeSH terms and keywords and their variants, including cannabis, cannabinoids, cannabidiol, CBD, THC, marijuana, edible, pregnancy, pregnant, prenatal, perinatal, postnatal, breastfeed, breastfed, lactation, nursing, fetus, fetal, neonatal, newborn, and child. In terms of publication type, all clinical trials, observational studies, reviews (including systematic reviews and meta-analyses), guidelines, and conference consensus statements were included. The main inclusion criteria were pregnant and breastfeeding women as the target population, and exposure to cannabis as the intervention of interest. VALIDATION METHODS: The authors rated the quality of evidence and strength of recommendations using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. See online Appendix A (Tables A1 for definitions and A2 for interpretations of strong and weak recommendations). INTENDED AUDIENCE: All health care providers who care for women of reproductive age. SUMMARY STATEMENTS: RECOMMENDATIONS.

The Canadian Women's Heart Health Alliance Atlas on the Epidemiology, Diagnosis, and Management of Cardiovascular Disease in Women - Chapter 4: Sex- and Gender-Unique Disparities: CVD Across the Lifespan of a Woman.

Women have unique sex- and gender-related risk factors for cardiovascular disease (CVD) that can present or evolve over their lifespan. Pregnancy-associated conditions, polycystic ovarian syndrome, and menopause can increase a woman's risk of CVD. Women are at greater risk for autoimmune rheumatic disorders, which play a role in the predisposition and pathogenesis of CVD. The influence of traditional CVD risk factors (eg, smoking, hypertension, diabetes, obesity, physical inactivity, depression, anxiety, and family history) is greater in women than men. Finally, there are sex differences in the response to treatments for CVD risk and comorbid disease processes. In this Atlas chapter we review sex- and gender-unique CVD risk factors that can occur across a woman's lifespan, with the aim to reduce knowledge gaps and guide the development of optimal strategies for awareness and treatment.

Les femmes présentent des facteurs de risque de maladies cardiovasculaires (MCV) uniques, liés au sexe et au genre, qui peuvent se manifester ou évoluer tout au long de leur vie. Les troubles médicaux associés à la grossesse, le syndrome des ovaires polykystiques et la ménopause peuvent augmenter le risque de MCV chez une femme. Les femmes sont plus exposées aux troubles rhumatologiques auto-immuns, qui jouent un rôle dans la prédisposition et dans la pathogenèse des MCV. L'influence des facteurs de risque traditionnels pour les MCV (par exemple, le tabagisme, l'hypertension, le diabète, l'obésité, la sédentarité, la dépression, l'anxiété et les antécédents familiaux) est plus importante chez les femmes que chez les hommes. Enfin, il existe des différences entre les sexes dans la réponse aux traitements du risque de MCV et des processus pathologiques comorbides. Dans ce chapitre de l'Atlas, nous passons en revue les facteurs de risque de MCV propres au sexe et au genre qui peuvent survenir tout au long de la vie d'une femme, dans le but de réduire les lacunes dans les connaissances et d'orienter l'élaboration de stratégies optimales de sensibilisation et de traitement.

Vaping During Pregnancy: What Are the Potential Health Outcomes and Perceptions Pregnant Women Have?

The prevalence of electronic nicotine delivery systems, such as vaping, is a growing public health concern, and there is limited information on the use of these devices during pregnancy. The objective of this rapid review was to summarize the available literature on human studies of the potential maternal or fetal health effects of vaping or women's perceptions of vaping during pregnancy. A systematic search was completed in the following databases: Medline, EMBASE, Scopus, Web of Science, and CINAHL. A search strategy was developed combining the terms pregnancy and vaping. Findings were divided into two groups and summarized as: 1) Health outcomes following vaping during pregnancy; and 2) Perceptions pregnant women have related to vaping during pregnancy. A total of 760 articles were retrieved and, after applying the inclusion/exclusion criteria and screening, 19 studies were included. Five included studies provided evidence on potential health outcomes and 14 were focused on perceptions. There is emerging evidence that vaping during pregnancy may increase the risk of small for gestational age newborns. Pregnant women generally report that they used vaping products during pregnancy for smoking cessation and perceived that this was a healthier alternative to traditional cigarettes. Overall, there was consensus that there is a lack of information on maternal and fetal health outcomes following vaping during pregnancy. Based on the findings of this rapid review, there is an urgent need for high-quality studies in pregnant women to evaluate the potential in utero and long-term effects of exposure to prenatal vaping.

Guideline No. 405: Screening and Counselling for Alcohol Consumption During Pregnancy.

OBJECTIVE: To establish national standards of care for screening and counselling pregnant women and women of child-bearing age about alcohol consumption and possible alcohol use disorder based on current best evidence. INTENDED USERS: Health care providers who care for pregnant women and women of child-bearing age. TARGET POPULATION: Pregnant women and women of child-bearing age and their families. EVIDENCE: Medline, EMBASE, and CENTRAL databases were searched for "alcohol use and pregnancy." The results were filtered for a publication date between 2010 and September 2018. The search terms were developed using Medical Subject Headings terms and keywords, including pre-pregnancy, pregnant, breastfeeding, lactation, female, women, preconception care, prenatal care, fetal alcohol spectrum disorder, prenatal alcohol exposure, drinking behavior, alcohol abstinence, alcohol drinking, binge drinking, alcohol-related disorders, alcoholism, alcohol consumption, alcohol abuse, benzodiazepines, disulfiram, naltrexane, acamprosate, ondansetron, topiramate, cyanamide, calcium carbimide, alcohol deterrents, disease management, detoxification, Alcoholics Anonymous, alcohol counselling, harm reduction, pre-pregnancy care, prenatal care, incidence, prevalence, epidemiological monitoring, and brief intervention. Evidence was included from clinical trials, observational studies, reviews, systematic reviews and meta-analyses, guidelines, and conference consensus. VALIDATION METHODS: The content and recommendations in this guideline were drafted and agreed upon by the authors. The Board of Directors of the Society of Obstetricians and Gynaecologists of Canada approved the final draft for publication. The quality of evidence was rated using the criteria described in the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology framework. BENEFITS, HARMS, COSTS: Implementation of the recommendations in these guidelines using validated screening tools and brief intervention approaches may increase obstetrical care provider recognition of alcohol consumption and problematic alcohol use among women of child-bearing age and those who are pregnant. It is anticipated that health care providers will become confident and competent in managing and supporting these women so they can achieve optimal health and pregnancy outcomes. SUMMARY STATEMENTS (GRADE RATINGS IN PARENTHESES): RECOMMENDATIONS (GRADE RATINGS IN PARENTHESES).

Fructose stimulated de novo lipogenesis is promoted by inflammation.

Benign hepatosteatosis, affected by lipid uptake, de novo lipogenesis and fatty acid (FA) oxidation, progresses to non-alcoholic steatohepatitis (NASH) on stress and inflammation. A key macronutrient proposed to increase hepatosteatosis and NASH risk is fructose. Excessive intake of fructose causes intestinal-barrier deterioration and endotoxaemia. However, how fructose triggers these alterations and their roles in hepatosteatosis and NASH pathogenesis remain unknown. Here we show, using mice, that microbiota-derived Toll-like receptor (TLR) agonists promote hepatosteatosis without affecting fructose-1-phosphate (F1P) and cytosolic acetyl-CoA. Activation of mucosal-regenerative gp130 signalling, administration of the YAP-induced matricellular protein CCN1 or expression of the antimicrobial peptide Reg3b (beta) peptide counteract fructose-induced barrier deterioration, which depends on endoplasmic-reticulum stress and subsequent endotoxaemia. Endotoxin engages TLR4 to trigger TNF production by liver macrophages, thereby inducing lipogenic enzymes that convert F1P and acetyl-CoA to FA in both mouse and human hepatocytes.

What constitutes patient-centred care for women: a theoretical rapid review.

BACKGROUND: Women experience disparities in health care delivery and outcomes. Patient-centred care for women (PCCW) is needed. This study examined how PCC has been conceptualized and operationalized in women's health research. METHODS: We conducted a theoretical rapid review of PCCW in MEDLINE, EMBASE, CINAHL and SCOPUS from 2008 to 2018 for studies involving women aged 18 years or greater with any condition, and analyzed data using an established 6-domain framework of patient-centred communication. RESULTS: We included 39 studies, which covered the following clinical areas: maternal care, cancer, diabetes, HIV, endometriosis, dementia, distal radius fracture, overactive bladder, and lupus erythematosus. The 34 (87.2%) studies that defined or described PCC varied in the PCC elements they addressed, and none addressed all 6 PCC domains. Common domains were exchanging information (25, 73.5%) and fostering the patient-clinician relationship (22, 64.7%). Fewer studies addressed making decisions (16, 47.1%), enabling patient self-management (15, 44.1%), responding to emotions (12, 35.3%), or managing uncertainty (1, 2.9%). Compared with mixed-gender studies, those comprised largely of women more frequently prioritized exchanging information above other domains. Few studies tested strategies to support PCCW or evaluated the impact of PCCW; those that did demonstrated beneficial impact on patient knowledge, satisfaction, well-being, self-care and clinical outcomes. CONCLUSIONS: Studies varied in how they conceptualized PCCW, and in many it was defined narrowly. Few studies examined how to implement or measure PCCW; thus, we lack insight on how to operationlize PCCW. Thus, further research is needed to confirm this, and whether PCCW differs across conditions, knowledge needed to inform policies, guidelines and measures aimed at improving health care and associated outcomes for women.

Screening and Management of Substance Use in Pregnancy: A Review.

Substance use during pregnancy has important implications for health care providers, policy makers, and can negatively impact a woman's health and the health of her children. Understanding trends, patterns of use and outcomes are critical to prevention campaigns, building awareness, and providing effective care. This review will discuss the current therapeutic approaches and recommendations for screening and patient management for substance use in pregnancy and during the postpartum period, and it is geared towards any care providers who care for patients or those who may care for patients who may be at risk for substance use during pregnancy.

Regulation of substrate utilization by the mitochondrial pyruvate carrier.

Pyruvate lies at a central biochemical node connecting carbohydrate, amino acid, and fatty acid metabolism, and the regulation of pyruvate flux into mitochondria represents a critical step in intermediary metabolism impacting numerous diseases. To characterize changes in mitochondrial substrate utilization in the context of compromised mitochondrial pyruvate transport, we applied (13)C metabolic flux analysis (MFA) to cells after transcriptional or pharmacological inhibition of the mitochondrial pyruvate carrier (MPC). Despite profound suppression of both glucose and pyruvate oxidation, cell growth, oxygen consumption, and tricarboxylic acid (TCA) metabolism were surprisingly maintained. Oxidative TCA flux was achieved through enhanced reliance on glutaminolysis through malic enzyme and pyruvate dehydrogenase (PDH) as well as fatty acid and branched-chain amino acid oxidation. Thus, in contrast to inhibition of complex I or PDH, suppression of pyruvate transport induces a form of metabolic flexibility associated with the use of lipids and amino acids as catabolic and anabolic fuels.

Tracing compartmentalized NADPH metabolism in the cytosol and mitochondria of mammalian cells.

Eukaryotic cells compartmentalize biochemical processes in different organelles, often relying on metabolic cycles to shuttle reducing equivalents across intracellular membranes. NADPH serves as the electron carrier for the maintenance of redox homeostasis and reductive biosynthesis, with separate cytosolic and mitochondrial pools providing reducing power in each respective location. This cellular organization is critical for numerous functions but complicates analysis of metabolic pathways using available methods. Here we develop an approach to resolve NADP(H)-dependent pathways present within both the cytosol and the mitochondria. By tracing hydrogen in compartmentalized reactions that use NADPH as a cofactor, including the production of 2-hydroxyglutarate by mutant isocitrate dehydrogenase enzymes, we can observe metabolic pathway activity in these distinct cellular compartments. Using this system we determine the direction of serine/glycine interconversion within the mitochondria and cytosol, highlighting the ability of this approach to resolve compartmentalized reactions in intact cells.

IDH1 mutations alter citric acid cycle metabolism and increase dependence on oxidative mitochondrial metabolism.

Oncogenic mutations in isocitrate dehydrogenase 1 and 2 (IDH1/2) occur in several types of cancer, but the metabolic consequences of these genetic changes are not fully understood. In this study, we performed (13)C metabolic flux analysis on a panel of isogenic cell lines containing heterozygous IDH1/2 mutations. We observed that under hypoxic conditions, IDH1-mutant cells exhibited increased oxidative tricarboxylic acid metabolism along with decreased reductive glutamine metabolism, but not IDH2-mutant cells. However, selective inhibition of mutant IDH1 enzyme function could not reverse the defect in reductive carboxylation activity. Furthermore, this metabolic reprogramming increased the sensitivity of IDH1-mutant cells to hypoxia or electron transport chain inhibition in vitro. Lastly, IDH1-mutant cells also grew poorly as subcutaneous xenografts within a hypoxic in vivo microenvironment. Together, our results suggest therapeutic opportunities to exploit the metabolic vulnerabilities specific to IDH1 mutation.