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Sustained Diet-Induced Remission in Pediatric Crohn's Disease Is Associated With Kynurenine and Serotonin Pathways.
Ghiboub, M, Boneh, RS, Sovran, B, Wine, E, Lefèvre, A, Emond, P, Verburgt, CM, Benninga, MA, de Jonge, WJ, Van Limbergen, JE
Inflammatory bowel diseases. 2023;29(5):684-694
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Crohn’s disease (CD) is an inflammatory bowel disease associated with alterations in intestinal tryptophan metabolism, in particular with increases in metabolites of the kynurenine pathway and decreased metabolites of the serotonin pathway. The aim of this 12-week randomised clinical study was to evaluate the effect of CD exclusion diet with partial enteral nutrition (CDED+PEN) and exclusive enteral nutrition (EEN) on intestinal tryptophan metabolism (as measured in faeces) in 43 children with mild-to-moderate CD. 13 of 15 patients on CDED+PEN and 9/13 on EEN achieved remission at week 6, and 8/9 and 6/9 patients, respectively, maintained remission at 12 weeks. Some kynurenine pathway metabolites decreased and some serotonin metabolites increased, in patients who achieved induction and maintenance of remission. These changes were similar in both intervention groups. On the other hand, in patients on EEN who did not go into remission, these changes were not observed. The authors concluded that further studies are warranted to inform whether there is a causal link and to refine nutritional interventions.
Abstract
BACKGROUND Both the Crohn's disease exclusion diet combined with partial enteral nutrition (CDED+PEN) and exclusive enteral nutrition (EEN) can induce remission in mild-to-moderate pediatric Crohn's disease and are associated with a marked decrease in fecal kynurenine levels. This suggests a link between clinical outcome of dietary therapy and changes in tryptophan metabolism pathways. Here, we characterize the changes in several fecal tryptophan metabolites induced by CDED+PEN or EEN and their association with remission. METHODS A total of 21 tryptophan metabolites were quantified in fecal samples from a 12-week prospective randomized trial with CDED+PEN or EEN for induction of remission in mild to moderate pediatric Crohn's disease. Tryptophan metabolites at week 0 (W0), W6, and W12 of 73 samples were quantitatively measured by liquid chromatography coupled with triple quadrupole mass spectrometry, and data were analyzed according to clinical groups of baselines (W0), induced remission at W6, no remission, sustained remission at W12, and nonsustained remission. RESULTS Reduction in components of the kynurenine pathway, such as kynurenine and quinolinic acid, were strongly associated with induced remission with both CDED+PEN and EEN, which were maintained in sustained remission. Specific serotonin pathway metabolites, such as melatonin, N-acetylserotonin, and 5-OH-tryptophan, were significantly increased in fecal samples from patients maintaining remission at W12 with both CDED+PEN and EEN. Importantly, in samples from patients failing to sustain remission, no changes were observed. Remission induction with EEN differs from CDED+PEN, particularly the moderate effects on indole pathway metabolites. The ratios of kynurenine and melatonin and quinolinic acid and melatonin perform well as markers for sustained remission. CONCLUSIONS The reduction in specific kynurenine pathway compounds and the increase in serotonin pathway compounds are associated with diet-induced and sustained remission. Further studies are warranted to assess causality and the association of these metabolites with specific diet and lifestyle factors, affecting sustained clinical remission. We show that fecal tryptophan metabolites are associated with remission following dietary therapy in a prospective clinical trial of pediatric Crohn’s disease patients. Our study shows that reduction in some kynurenine pathway metabolites and the increase in serotonin pathway compounds are associated with diet-induced and sustained remission. These compounds may play a role in mediating the mechanism of action of dietary therapy.
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The Efficacy of Self-Management Strategies for Females with Endometriosis: a Systematic Review.
Mardon, AK, Leake, HB, Hayles, C, Henry, ML, Neumann, PB, Moseley, GL, Chalmers, KJ
Reproductive sciences (Thousand Oaks, Calif.). 2023;30(2):390-407
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Endometriosis is a gynaecological condition with symptoms of pelvic pain, fatigue, and stress. Decreased quality of life, impaired fertility and hinderances to carry out day to day tasks are all associated with endometriosis. Treatment options involve medications and surgery; however, both are associated with poorer outcomes than the initial disease itself. Self-management strategies that the individual can perform themselves, such as lifestyle changes, meditation, and rest have all been used to improve the quality of life of individuals with endometriosis, however their effectiveness has not been determined. This systematic review and meta-analysis aimed to determine the effectiveness of self-management strategies for the management of endometriosis. The study showed that many self-management strategies were no more effective than placebo or hormonal therapies for the management of endometriosis. It was concluded that many self-management strategies were no more effective than hormonal treatment at reducing endometriosis symptoms and the studies that did show a benefit were insufficient to base recommendations on due to poor design. This study could be used by healthcare professionals to understand that currently the research on self-management strategies of endometriosis is poor and whilst some may be of benefit to individuals who cannot or do not want to take hormone therapy, more research is warranted.
Expert Review
Conflicts of interest:
None
Take Home Message:
It is not possible to generalise the findings of this systematic review for the self-management of endometriosis due to the poor quality of evidence. Further studies of higher quality are needed.
Evidence Category:
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A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
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B: Systematic reviews including RCTs of limited number
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C: Non-randomized trials, observational studies, narrative reviews
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D: Case-reports, evidence-based clinical findings
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E: Opinion piece, other
Summary Review:
Introduction
Endometriosis is an inflammatory condition where endometrial-like tissue is found outside of the uterus. Diagnosis of endometriosis is made in around 6-10% of females of reproductive age. Endometriosis can adversely affect fertility, psychological well being and quality of life (QoL). Conventional interventions can have side effects and limited effectiveness. The aim of this systematic review (SR) was to evaluate the efficacy of self-management interventions for pain-related symptoms and QoL.
Methods
Fifteen experimental studies were included in this SR. Ten evaluated dietary supplements, three evaluated dietary modifications, one evaluated over-the-counter (OTC) medication, and one evaluated exercise. Outcome measures were self-reported for dysmenorrhoea, dyspareunia, overall pain, non-menstrual pelvic pain, use of medications and QoL.
Results
- Most dietary supplements were no more effective than placebo or frequently recommended medical interventions, at reducing pain-related outcomes.
- Melatonin (one RCT n=30) performed better than placebo for managing dysmenorrhoea and overall pain but not for non-menstrual pelvic pain. PEA-transploydatin (one RCT n=20) performed better than placebo for dysmenorrhoea and non-menstrual pelvic pain but not better than medical intervention.
- Resveratrol (one RCT n=22 & one intervention study n=12) plus the oral contraceptive pill (OCP) was more effective than the OCP alone for managing dysmenorrhoea.
- In one observational study, 75% of participants (n=295) reported a reduction in ‘high’ intensity pain scores following a 12-month gluten-free diet (p- value =<0.005). Similarly, a full dietary modification (one non randomised controlled trial , n=30) found less participants reporting pain at ‘high intensity’ (18%) compared to linseed and calcium oil supplements (41%) and placebo (62%).
- A metal trace element supplement was more effective than placebo for managing overall pain (one RCT p- value<0.001).
- Naproxen (one cross over trial, n=11) performed better than placebo at managing dysmenorrhoea (83% vs 41%, p- value 0.008).
- Hatha yoga (one RCT n=12) was found to be effective at reducing overall pain and improving QoL compared to no yoga (p-value <0.05).
Conclusion
Due to limited, low-quality evidence, high risk of bias and high levels of heterogeneity between studies, it was not possible to generalise the findings of the studies included in this systematic review. Further research of high-quality is needed in order to make self-management recommendations for females with endometriosis.
Notes: The authors reported no conflicts of interest.
Clinical practice applications:
Evidence-based self-management interventions are considered critical for the management of endometriosis. However, the quality of evidence in this SR was considered of poor quality. Further high-quality research is needed in order to be able to make recommendations. Strategies that showed potential benefits included:
- Dietary modifications and a gluten-free diet may be effective for reducing the intensity of pain associated with endometriosis.
- Hatha yoga may be effective at reducing overall pain and supporting psychological wellbeing and QoL.
Considerations for future research:
High quality studies are needed as well as a ‘gold standard’ definition for self-management criteria. Understanding potential barriers to self-management interventions may also be beneficial.
Abstract
Self-management is critical for the care of endometriosis. Females with endometriosis frequently use self-management strategies to manage associated symptoms; however, the efficacy of such strategies is unknown. The aim of this review was to systematically appraise the evidence concerning efficacy of self-management strategies for endometriosis symptoms. Electronic databases, including Medline, Embase, Emcare, Web of Science Core Collection, Scopus, and the Cochrane Central Register of Controlled Trials, were searched from inception to March 2021. We included peer-reviewed experimental studies published in English evaluating the efficacy of self-management strategies in human females laparoscopically diagnosed with endometriosis. Studies underwent screening, data extraction, and risk of bias appraisal (randomised studies: Risk of Bias 2 tool; non-randomised studies: Risk Of Bias In Non-randomized Studies - of Interventions tool). Of the fifteen studies included, 10 evaluated dietary supplements, three evaluated dietary modifications, one evaluated over-the-counter medication, and one evaluated exercise. Most studies had a high-critical risk of bias. Many self-management strategies were not more effective at reducing endometriosis symptoms compared to placebo or hormonal therapies. Where studies suggest efficacy for self-management strategies, no recommendations can be made due to the poor quality and heterogeneity of evidence. High-quality empirical evidence is required to investigate the efficacy of self-management strategies for females with endometriosis.
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Metabolic dysfunction-associated fatty liver disease and cardiovascular disease: A meta-analysis.
Wen, W, Li, H, Wang, C, Chen, C, Tang, J, Zhou, M, Hong, X, Cheng, Y, Wu, Q, Zhang, X, et al
Frontiers in endocrinology. 2022;13:934225
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Non-alcoholic fatty liver disease (NAFLD) is a multi-system disease that not only affects the structure and function of the liver but also increases the incidence of type 2 diabetes, cardiovascular disease (CVD), cerebrovascular disease, and chronic kidney disease. In 2020, experts reached a consensus to recommend a more appropriate term to more accurately and positively define fatty liver disease associated with metabolic disorders, namely, metabolic dysfunction-associated fatty liver disease (MAFLD). The aim of this study was to investigate the risk of CVD incidence or CVD mortality in patients diagnosed with MAFLD. This study is a meta-analysis of ten cohort studies. Results show that patients in the MAFLD group had a significantly increased relative risk of CVD or death from CVD during the follow-up compared with the control group. Authors conclude that even though there is a positive association between MAFLD and the risk of CVD or death from CVD, further studies are needed to demonstrate different effects of the newly defined MAFLD on CVD compared with previous NAFLD.
Abstract
BACKGROUND Metabolic dysfunction-associated fatty liver disease [MAFLD, formerly known as nonalcoholic fatty liver disease (NAFLD)] is one of the most important causes of liver disease worldwide, while cardiovascular disease (CVD) is still one of the main causes of morbidity and mortality worldwide, and the two are closely related. This study aimed to investigate the risk of CVD incidence or CVD-related mortality (CVD mortality) in patients diagnosed with MAFLD under new concepts and new diagnostic criteria. METHODS We searched English databases PubMed, Web of Science, Embase, and Cochrane Library for relevant literature. The language was restricted to English. RESULTS By 22 January 2022, 556 published studies were obtained through preliminary retrieval, and 10 cohort studies were included in this study. All statistical analyses were performed using Review Manager 5.2 software. Compared with the control group, patients in the MAFLD group had a significantly higher relative risk of CVD incidence or CVD mortality during the follow-up, with an RR rate of 1.95 (95% CI 1.76-2.17, p < 0.01). The incidence of CVD in the MAFLD group was more than twice that in the control group (RR 2.26, 95% CI 2.00-2.54, p < 0.01). The mortality rate of CVD was 1.57 times higher than that in the control group (RR 1.57, 95% CI 1.42-1.72, p < 0.01). CONCLUSIONS Patients diagnosed with MAFLD alone had higher cardiovascular mortality than those diagnosed with NAFLD alone based on the available data.
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Menopause experience in First Nations women and initiatives for menopause symptom awareness; a community-based participatory research approach.
Sydora, BC, Graham, B, Oster, RT, Ross, S
BMC women's health. 2021;21(1):179
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Little research has been conducted about menopause in First Nations women. In response to the wishes of Cree women living in Maskwacis, Alberta, a community-based participatory research (CBPR) project was conducted to explore menopause experience and raise awareness of menopause symptoms in the community. Local women between the ages of 40–65 years were invited to participate in workshops, they also completed questionnaires. The five workshops included a total of 37, mostly post-menopausal women. The main discussion themes were: ‘experiences of menopause symptoms’ including their impact on quality of life; ‘menopause knowledge prior to their own experience’ with most women feeling that they had insufficient information before menopause; ‘menopause symptom management’ which mainly included practical strategies; ‘impact of menopause on family members’ which was of prime concern with uncontrollable mood changes affecting the whole family and sometimes causing matrimonial disharmony. These workshops identified a need for increasing menopause awareness, particularly for partners and other family members.
Abstract
BACKGROUND Little research has been conducted about menopause in First Nations women. In response to the wishes of Cree women living in Maskwacis, Alberta, to start a dialogue on menopause, we undertook community-based participatory research (CBPR) to explore menopause experience and raise awareness of menopause symptoms in the community. METHODS The research adhered to the principles of Ownership, Control, Access and Possession (OCAP™) and was guided by the interest of the participating women. Local women (target age 40-65 years) were invited to participate in workshops using word-of-mouth and community posters in health centers. Five research workshops were held in community settings, attended by experienced women's health researchers and consenting women. The participants guided the informal discussions. They also completed questionnaires which included menopause-related quality of life. The researchers used extensive hand-written field notes to record data; qualitative content analysis was applied to identify themes. Simple descriptive analysis was used for the questionnaire results. The findings were discussed at a community feedback session and laid the basis for further knowledge translation initiatives. RESULTS The five workshops included a total of 37, mostly post-menopausal women with 6-11 women/workshop. The main discussion themes were: "experiences of menopause symptoms" including their impact on quality of life; "menopause knowledge prior to their own experience" with most women feeling that they had insufficient information before menopause; "menopause symptom management" which mainly included practical strategies; "impact of menopause on family members" which was of prime concern with uncontrollable mood changes affecting the whole family and sometimes causing matrimonial disharmony. Questionnaire responses corroborated the workshop discussions. Knowledge translation of the research findings produced two information pamphlets specifically for the Maskwacis community: one for husband/partner, the other for women and family members. These pamphlets have been distributed in all areas of the community. CONCLUSION This CBPR project addressed a topic identified by the community as being important. Community members developed informative pamphlets in response to the women's concern of lack of understanding for menopause symptoms among families. This simple solution has been widely accepted by community members, opening the possibility of wider discussion about menopause.
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Total estimated usual nutrient intake and nutrient status biomarkers in women of childbearing age and women of menopausal age.
Devarshi, PP, Legette, LL, Grant, RW, Mitmesser, SH
The American journal of clinical nutrition. 2021;113(4):1042-1052
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Nutritional needs vary depending on the stage in a woman’s lifecycle. Women of child-bearing age (WCBA) and women of menopausal age (WMENO) are at high risk of not meeting required nutrient amounts, yet data is limited on nutrient intakes in these groups. This observational study of 4134 WCBA and 3438 WMENO aimed to determine any nutrient gaps and if associations exist between dietary intake and blood levels of key nutrients. The results showed that WCBA and WMENO had inadequate dietary intakes of calcium, magnesium, and vitamins A, C, D and E, which was allevaited by supplementation. Women who had lower levels of folate, vitamins D, B12 and essential fatty acids had lower dietary intakes of these nutrients, indicating a risk of deficiency. It was concluded that many women of WCBA and WMENO may have inadequate dietary nutrient intake and supplementation may improve this. This study could be used by healthcare professionals to understand that nutrient intakes may be inadequate in WCBA and WMENO. Dietary recommendations to increase nutrient intake would be advisable, however if individuals are still not meeting nutrient requirements, nutrient supplementation may be advisable.
Abstract
BACKGROUND Women of childbearing age (WCBA) and women of menopausal age (WMENO) have distinct nutritional needs. Understanding nutrient intake and status in these life stages is critical for tailoring dietary recommendations. OBJECTIVES The objectives of this study were to evaluate total estimated usual nutrient intakes from food and food plus supplements and to compare these to established recommendations for WCBA and WMENO life stages and examine associations between self-reported estimated usual intakes and nutrient status biomarkers. METHODS Twenty-four-hour dietary recall data from 2011-2016 NHANES were used to estimate usual intake of nutrients from food and food plus supplements for WCBA (aged 15-44 y, n = 4,134) and WMENO (aged 40-65 y, n = 3,438). Estimates of mean usual intake were derived and compared across clinically defined nutrient biomarker categories. RESULTS Both young (aged 15-30 y) and older (aged 31-44 y) WCBA had intakes from food below the Estimated Average Requirement (EAR) for calcium (49% and 44%, respectively), magnesium (62%, 44%), and vitamins A (50%, 44%), C (47%, 46%), D (>97%, >97%), and E (92%, 88%). Similarly, perimenopausal (aged 40-50 y) and menopausal (aged 51-65 y) women had intakes from food below the EAR for calcium (48% and 74%, respectively), magnesium (50%, 49%), and vitamins A (44%, 37%), C (44%, 41%), D (>97%, >97%), and E (88%, 86%). Nutrient gaps decreased with supplement usage. For folate, vitamins D and B-12, and DHA, women in the lowest biomarker category (indicating increased risk of deficiency) had significantly lower intake from food (315.2 ± 25.9 compared with 463.8 ± 5.2 µg dietary folate equivalents, 3.5 ± 0.1 compared with 4.2 ± 0.1 µg, 3.6 ± 0.2 compared with 4.3 ± 0.1 µg, and 0.037 ± 0.005 compared with 0.070 ± 0.006 g, respectively; P < 0.01) of the corresponding nutrient compared with the highest biomarker category. CONCLUSIONS Substantial percentages of WCBA and WMENO are not meeting recommendations for multiple nutrients, whereas supplement usage partially fills nutrient gaps. Dietary intake was positively associated with most nutrient status biomarkers. Specific guidance is needed to ensure adequate nutrient intakes and nutrient status during these critical life stages.
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Chinese herbal medicine for coronavirus disease 2019: A systematic review and meta-analysis.
Xiong, X, Wang, P, Su, K, Cho, WC, Xing, Y
Pharmacological research. 2020;160:105056
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Coronavirus- 2019 (COVID-19) infection, the cause of a global pandemic, can lead to respiratory failure and death. Whilst no specific antiviral drugs or vaccines were available in the early stages of the outbreak, in China Chinese Herbal Medicine (CHM) had been widely used since the beginning. This systematic review and meta-analysis compared the efficacy of CHM to conventional Western medicine treatments for COVID-19 infections, involving 2275 patients from 18 trials. The outcome suggested that the use of CHM exhibited many positive effects on the course of the disease, including fever severity, length of hospital stay, cough, fatigue, anti-inflammatory markers and lung imaging, therefore presenting a promising treatment for reducing the severity and duration of the disease, whilst having little to no side effects. The trials included various formulations predominantly based on traditional Chinese herbal medicine, with the therapeutic principles of ‘dispelling cold’, ‘relieving exterior’, ‘dissipating phlegm’, ‘clearing away heat’, ‘invigorating spleen’, and ‘replenishing qi’. In the included trials a total of 100 different herbs were identified. The five most frequently used herbs being Liquorice Root (Glycyrrhiza spp.), Baikal Skullcap Root (Scutellaria baicalensis), Pinellia Rhizome (Pinelliae tematae), Forsythia Fruit (Forsythia suspensa), and Bitter Apricot Seed (Armeniacae amarum). The treatment course ranged from 5 to 15 days and the most common dosage were tea preparations. The authors describe the meta-analysis as one of the larger ones conducted so far and briefly discuss some of the therapeutic effects and mechanisms of the herbs most used. This meta-analysis yields evidence for alternative strategies in the support and management of COVID-19 infections.
Abstract
Currently, coronavirus disease 2019 (COVID-19), which can lead to severe respiratory failure and death, is now a global pandemic with no specific anti-viral drugs or vaccines. However, It is worth noting that traditional Chinese medicine (TCM), especially Chinese herbal medicine (CHM), has been widely applied in mainland China since outbreak, bringing new hope for the prevention and control of COVID-19. A comprehensive literature searching was conducted in 7 electronic databases from their inception up to June 21, 2020 to evaluate the efficacy and safety of CHM for COVID-19. Eighteen randomized controlled trials (RCTs) involving 2275 patients were enrolled. Most of CHMs were originated from classical Chinese herbal formulas. Liquoric Root (Gancao, Radix Glycyrrhizae), Baical Skullcap Root (Huangqin, Radix Scutellariae Baicalensis), Pinellia Rhizome (Banxia, Rhizoma Pinelliae Tematae), Forsythia Fruit (Lianqiao, Fructus Forsythiae Suspensae), and Bitter Apricot Seed (Kuxingren, Semen Armeniacae Amarum) were most frequently used Chinese herbs. The most commonly used dosage formulation was decoction. Our meta-analyses found that comparing CHM group and conventional western medicine group, CHM group has improvements in several clinical parameters including lung CT, clinical cure rate, ranging from mild to critical cases, length of hospital stay, total score of clinical symptoms, fever reduction time, symptom score of fever, number of cough reduction cases, symptom score of cough, number of fatigue reduction cases, symptom score of fatigue, disappearing time of fatigue, TCM syndrome, viral nucleic acid testing, and inflammatory biomarkers (C-reactive protein). Besides, no severe adverse effects was identified by CHM. CHM, especially classical Chinese herbal formulas, could be used as potential candidates for COVID-19 in this battle.
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Fasting blood glucose at admission is an independent predictor for 28-day mortality in patients with COVID-19 without previous diagnosis of diabetes: a multi-centre retrospective study.
Wang, S, Ma, P, Zhang, S, Song, S, Wang, Z, Ma, Y, Xu, J, Wu, F, Duan, L, Yin, Z, et al
Diabetologia. 2020;63(10):2102-2111
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Hyperglycaemia was a risk factor for mortality from severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) and is an independent risk factor for lower respiratory tract infection and poor prognosis. The aim of this retrospective study of 605 patients without previously diagnosed diabetes was to examine the association between fasting blood glucose (FBG) on admission and the 28-day in hospital mortality of COVID-19 patients. Patients with a FBG level of 7.0mmol/l or over had more than double the risk of dying than those with a level of 6.0mmol/l or less. Other risk factors for mortality included age, being male, and severity of pneumonia at admission. Compared with patients whose FBG was 6.0mmol/l or lower at admission, patients with FBG of 7.0 mmol/l and above had a 3.99 times higher risk of in-hospital complications, whilst those with FBG of 6.1–6.9 mmol/l had a 2.61 times higher risk of complications. The authors conclude that glycaemic testing and control are important to all COVID-19 patients even where they have no pre-existing diabetes.
Abstract
AIMS/HYPOTHESIS Hyperglycaemia is associated with an elevated risk of mortality in community-acquired pneumonia, stroke, acute myocardial infarction, trauma and surgery, among other conditions. In this study, we examined the relationship between fasting blood glucose (FBG) and 28-day mortality in coronavirus disease 2019 (COVID-19) patients not previously diagnosed as having diabetes. METHODS We conducted a retrospective study involving all consecutive COVID-19 patients with a definitive 28-day outcome and FBG measurement at admission from 24 January 2020 to 10 February 2020 in two hospitals based in Wuhan, China. Demographic and clinical data, 28-day outcomes, in-hospital complications and CRB-65 scores of COVID-19 patients in the two hospitals were analysed. CRB-65 is an effective measure for assessing the severity of pneumonia and is based on four indicators, i.e. confusion, respiratory rate (>30/min), systolic blood pressure (≤90 mmHg) or diastolic blood pressure (≤60 mmHg), and age (≥65 years). RESULTS Six hundred and five COVID-19 patients were enrolled, including 114 who died in hospital. Multivariable Cox regression analysis showed that age (HR 1.02 [95% CI 1.00, 1.04]), male sex (HR 1.75 [95% CI 1.17, 2.60]), CRB-65 score 1-2 (HR 2.68 [95% CI 1.56, 4.59]), CRB-65 score 3-4 (HR 5.25 [95% CI 2.05, 13.43]) and FBG ≥7.0 mmol/l (HR 2.30 [95% CI 1.49, 3.55]) were independent predictors for 28-day mortality. The OR for 28-day in-hospital complications in those with FBG ≥7.0 mmol/l and 6.1-6.9 mmol/l vs <6.1 mmol/l was 3.99 (95% CI 2.71, 5.88) or 2.61 (95% CI 1.64, 4.41), respectively. CONCLUSIONS/INTERPRETATION FBG ≥7.0 mmol/l at admission is an independent predictor for 28-day mortality in patients with COVID-19 without previous diagnosis of diabetes. Glycaemic testing and control are important to all COVID-19 patients even where they have no pre-existing diabetes, as most COVID-19 patients are prone to glucose metabolic disorders. Graphical abstract.
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Comparison of dietary macronutrient patterns of 14 popular named dietary programmes for weight and cardiovascular risk factor reduction in adults: systematic review and network meta-analysis of randomised trials.
Ge, L, Sadeghirad, B, Ball, GDC, da Costa, BR, Hitchcock, CL, Svendrovski, A, Kiflen, R, Quadri, K, Kwon, HY, Karamouzian, M, et al
BMJ (Clinical research ed.). 2020;369:m696
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Dietary recommendations to combat obesity and its associated risk for heart disease are extensive. Many different diets and patterns of eating are being tried by millions of people, however no systematic review comparing their effectiveness has been performed. This systematic review and meta-analysis aimed to determine the effectiveness of 14 popular diets and diets which restrict certain nutrients on weight loss and heart disease risk. The results identified 121 studies with 21942 patients for inclusion. The Atkins diet, the Zone diet and the Dietary Approaches to Stop Hypertension (DASH) diet were the most effective for weight loss and for reducing blood pressure. Low carbohydrate and low-fat diets achieved similar weight loss when compared to a normal diet. Low carbohydrate diets had less effect on heart disease risk factors than low fat and moderate macronutrient diets. There were no improvements in good cholesterol with any of the diets. Interestingly any benefits on weight loss for any of the diets disappeared after 12 months and this was also observed for heart disease risk, except in those on the Mediterranean diet. It was concluded that most diets show improvements to weight loss and heart disease risk factors over 6 months, however these are largely unsustainable after 12 months. Differences between diets are small and healthcare practitioners could use this study to recommend any number of diets to achieve weight loss and the Mediterranean diet in particular to decrease heart disease risk. However, it is important to understand that this may be a short-term fix and at 12 months patients need to be assessed to ensure that weight loss is sustained.
Abstract
OBJECTIVE To determine the relative effectiveness of dietary macronutrient patterns and popular named diet programmes for weight loss and cardiovascular risk factor improvement among adults who are overweight or obese. DESIGN Systematic review and network meta-analysis of randomised trials. DATA SOURCES Medline, Embase, CINAHL, AMED, and CENTRAL from database inception until September 2018, reference lists of eligible trials, and related reviews. STUDY SELECTION Randomised trials that enrolled adults (≥18 years) who were overweight (body mass index 25-29) or obese (≥30) to a popular named diet or an alternative diet. OUTCOMES AND MEASURES Change in body weight, low density lipoprotein (LDL) cholesterol, high density lipoprotein (HDL) cholesterol, systolic blood pressure, diastolic blood pressure, and C reactive protein at the six and 12 month follow-up. REVIEW METHODS Two reviewers independently extracted data on study participants, interventions, and outcomes and assessed risk of bias, and the certainty of evidence using the GRADE (grading of recommendations, assessment, development, and evaluation) approach. A bayesian framework informed a series of random effects network meta-analyses to estimate the relative effectiveness of the diets. RESULTS 121 eligible trials with 21 942 patients were included and reported on 14 named diets and three control diets. Compared with usual diet, low carbohydrate and low fat diets had a similar effect at six months on weight loss (4.63 v 4.37 kg, both moderate certainty) and reduction in systolic blood pressure (5.14 mm Hg, moderate certainty v 5.05 mm Hg, low certainty) and diastolic blood pressure (3.21 v 2.85 mm Hg, both low certainty). Moderate macronutrient diets resulted in slightly less weight loss and blood pressure reductions. Low carbohydrate diets had less effect than low fat diets and moderate macronutrient diets on reduction in LDL cholesterol (1.01 mg/dL, low certainty v 7.08 mg/dL, moderate certainty v 5.22 mg/dL, moderate certainty, respectively) but an increase in HDL cholesterol (2.31 mg/dL, low certainty), whereas low fat (-1.88 mg/dL, moderate certainty) and moderate macronutrient (-0.89 mg/dL, moderate certainty) did not. Among popular named diets, those with the largest effect on weight reduction and blood pressure in comparison with usual diet were Atkins (weight 5.5 kg, systolic blood pressure 5.1 mm Hg, diastolic blood pressure 3.3 mm Hg), DASH (3.6 kg, 4.7 mm Hg, 2.9 mm Hg, respectively), and Zone (4.1 kg, 3.5 mm Hg, 2.3 mm Hg, respectively) at six months (all moderate certainty). No diets significantly improved levels of HDL cholesterol or C reactive protein at six months. Overall, weight loss diminished at 12 months among all macronutrient patterns and popular named diets, while the benefits for cardiovascular risk factors of all interventions, except the Mediterranean diet, essentially disappeared. CONCLUSIONS Moderate certainty evidence shows that most macronutrient diets, over six months, result in modest weight loss and substantial improvements in cardiovascular risk factors, particularly blood pressure. At 12 months the effects on weight reduction and improvements in cardiovascular risk factors largely disappear. SYSTEMATIC REVIEW REGISTRATION PROSPERO CRD42015027929.
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Brown Adipose Crosstalk in Tissue Plasticity and Human Metabolism.
Scheele, C, Wolfrum, C
Endocrine reviews. 2020;41(1)
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Brown adipose tissue (BAT) is an important contributor to the regulation of metabolism via cellular communication with organs such as liver, muscle, gut and central nervous system. BAT is important for heat generation and is at high levels in human infants. Levels of activation of BAT decline as we age and it has been shown that the amount of BAT is smaller and its activity reduced in those with obesity and type 2 diabetes. To date, there is no answer to efficiently restore functional BAT in aging and obese subjects. This review looks at experiments done on the factors secreted from active BAT (batokines). The review aims to provide a structure for the processes and cell types involved in BAT and the recent findings of BAT whole-body communication are discussed. Altogether, these findings demonstrate that BAT has an adaptive capacity. Studying batokines, offers an alternative approach to identify novel drug targets for metabolic regulation.
Abstract
Infants rely on brown adipose tissue (BAT) as a primary source of thermogenesis. In some adult humans, residuals of brown adipose tissue are adjacent to the central nervous system and acute activation increases metabolic rate. Brown adipose tissue (BAT) recruitment occurs during cold acclimation and includes secretion of factors, known as batokines, which target several different cell types within BAT, and promote adipogenesis, angiogenesis, immune cell interactions, and neurite outgrowth. All these processes seem to act in concert to promote an adapted BAT. Recent studies have also provided exciting data on whole body metabolic regulation with a broad spectrum of mechanisms involving BAT crosstalk with liver, skeletal muscle, and gut as well as the central nervous system. These widespread interactions might reflect the property of BAT of switching between an active thermogenic state where energy is highly consumed and drained from the circulation, and the passive thermoneutral state, where energy consumption is turned off. (Endocrine Reviews 41: XXX - XXX, 2020).
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COVID-19 infection: the perspectives on immune responses.
Shi, Y, Wang, Y, Shao, C, Huang, J, Gan, J, Huang, X, Bucci, E, Piacentini, M, Ippolito, G, Melino, G
Cell death and differentiation. 2020;27(5):1451-1454
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The SARS-CoV-2 infection triggers an immune response which varies greatly from one person to another. It can be roughly divided into three stages: stage I, an asymptomatic incubation period with or without detectable virus; stage II, non-severe symptomatic period with the presence of virus; stage III, severe respiratory symptomatic stage with high viral load. Currently around 15% of people infected end up in severe stage III. There appears to be a two-phase immune response; an early protective phase and a second inflammation-driven damaging phase. In phase one the adaptive immune system responds to the virus. Being in good general health is important in this phase to limiting the progression of the disease to a more severe stage. In phase two the innate immune system response to tissue damage caused by the virus could lead to widespread inflammation of the lungs and acute respiratory distress syndrome or respiratory failure. Therapeutically this raises the question of whether the immune response should be boosted in phase one and suppressed in phase two. There also appears to be an element of viral relapse in some patients discharged from hospital indicating that a virus-eliminating immune response may be difficult to achieve naturally. These same patients may also not respond to vaccines. Overall, it is still unclear why some people develop severe disease, whilst others do not. Overall immunity alone does not explain the differences in disease presentation.