Erythroderma (exfoliative dermatitis). Part 2: energy homeostasis and dietetic management strategies.

Erythroderma (exfoliative dermatitis) is associated with important metabolic changes that include an enhancement in energy expenditure. The key components to total energy expenditure (TEE) include basal metabolic rate (~68% of TEE), physical activity (~22% of TEE) and thermic effect of food (~10% of TEE). In the erythrodermic state, there are likely multiple contributors to the increase in basal metabolic rate, such as 'caloric drain' resulting from increased evaporation of water from enhanced transepidermal water loss, increased activity of the cardiovascular system (including high-output cardiac failure), increased nonshivering thermogenesis and hormonal changes such as hypercortisolaemia. A change in the patient's level of physical activity and appetite as a result of ill health status may further impact on their TEE and energy consumption. In Part 2 of this two-part concise review, we explore the key constituents of energy homeostasis and the potential mechanisms influencing energy homeostasis in erythroderma, and suggest much-needed dietetic management strategies for this important condition.

Erythroderma (exfoliative dermatitis). Part 1: underlying causes, clinical presentation and pathogenesis.

Erythroderma (exfoliative dermatitis), first described by Von Hebra in 1868, manifests as a cutaneous inflammatory state, with associated skin barrier and metabolic dysfunctions. The annual incidence of erythroderma is estimated to be 1-2 per 100 000 population in Europe with a male preponderance. Erythroderma may present at birth, or may develop acutely or insidiously (due to progression of an underlying primary pathology, including malignancy). Although there is a broad range of diseases that associate with erythroderma, the vast majority of cases result from pre-existing and chronic dermatoses. In the first part of this two-part concise review, we explore the underlying causes, clinical presentation, pathogenesis and investigation of erythroderma, and suggest potential treatment targets for erythroderma with unknown causes.

Decreased plasma chemerin levels in women with gestational diabetes mellitus.

AIMS: To evaluate fasting and post-prandial serum chemerin levels in pregnant women with and without gestational diabetes, and again following delivery when normal glucose homeostasis is re-established. METHODS: Chemerin levels were measured in serum from nine women with gestational diabetes, and from eight age- and BMI-matched pregnant women with normal glucose tolerance during two meal tests: in the third trimester and 3-4 months post partum. All women with gestational diabetes re-established normal glucose tolerance after delivery. RESULTS: Meal intake did not affect serum chemerin levels. The group with gestational diabetes had lower mean serum chemerin levels during the third trimester compared with the group with normal glucose tolerance (28 ± 1.3 vs. 88 ± 3.5 ng/ml, P < 0.0001). In the group with normal glucose tolerance, mean serum chemerin levels decreased significantly post partum to 57 ± 2.8 ng/ml (P = 0.0001), but remained significantly (P = 0.0003) higher than post-partum levels in the group with gestational diabetes (31 ± 1.9 ng/ml), which did not differ significantly from third trimester levels (P = 0.31). CONCLUSIONS: Normal pregnancy is associated with increased circulating chemerin levels, which may act to reduce pregnancy-induced insulin resistance and prevent glucose intolerance. Women with gestational diabetes, however, have severely reduced chemerin levels that remain low after delivery, which may contribute to the insulin resistance, glucose intolerance and high type 2 diabetes risk associated with gestational diabetes.

A pilot study to assess the feasibility and uptake of MindDEC, a mindfulness-based self-management course for type 2 diabetes.

OBJECTIVE: The study aimed to investigate the feasibility of a remote mindfulness based self-management intervention for individuals with type 2 diabetes. It is important to further our understanding of how to improve self-management to improve health outcomes and low levels of uptake to self-management courses. METHOD: 29 participants with type 2 diabetes were recruited from the University Hospital Coventry and Warwickshire NHS trust. Three groups of participants engaged with a remote mindfulness based self-management intervention, which were delivered sequentially. After each intervention was complete, patient feedback was retrieved and implemented into the following intervention. The quantitative analysis comprised of descriptive statistics, independent sample t-test, paired sample t-test and multiple regression analysis. A qualitative analysis was also conducted through reflexive thematic analysis (RTA) to understand participant's perspective on the intervention. RESULTS: There was a total of 17 who attended the course (59 %) and a total drop out of 12 participants over the three courses (41 %). The qualitative findings reported three main themes: (1) Eating to manage my emotions rather than my diabetes (2) Implementing mindfulness has helped me manage my emotions (3) Medication rather than self-management behaviours control my diabetes. The focus group feedback included participants' appreciation of the community aspect of the intervention and their perception that the current course was more interactive compared to previous interventions. In addition, participants highlighted the importance of offering the course at an earlier stage of diagnosis to provide further support at the beginning of their diabetes journey. No significant findings were reported for the independent sample t-test, paired sample t-test and multiple regression analysis. CONCLUSION: The qualitative findings suggested that the course was beneficial, especially in demonstrating how mindfulness could aid self-management for individuals living with type 2 diabetes. Further funding and trials are warranted to improve the quality of technology used and to assess impact on diabetes control and mental health.

Neuroendocrine and endocrine dysfunction in the hyperinsulinemic PCOS patient: the role of metformin.

Metformin is a widely used and extensively studied insulin sensitising drug for the treatment of women with polycystic ovary syndrome (PCOS), with various actions in tissues responding to insulin that include the liver, skeletal muscle, adipose tissue, the endothelium of blood vessels, and the ovaries. Treatment of PCOS women with metformin has been shown to reduce fasting glucose levels, blood pressure, and serum androgens; further effects of metformin in women with PCOS may include direct effects on the central nervous system; and indirect effects via the modification of gut hormone and adipokine synthesis and/or secretion. A number of "novel" adipokines and metabolic factors have been recently identified which may play a role both in the pathogenesis and the treatment of women with PCOS. We here discuss recent advances in the area, with a focus on neuroendocrine and endocrine dysfunctions in women with PCOS and the potential role of metformin in this context.

Phosphoprotein enriched in diabetes gene product (Ped/pea-15) is increased in omental adipose tissue of women with the polycystic ovary syndrome: ex vivo regulation of ped/pea-15 by glucose, insulin and metformin.

Polycystic ovary syndrome (PCOS), the commonest endocrine disorder in women, is characterized by an altered steroid milieu and is associated with insulin resistance and type 2 diabetes mellitus (T2DM). Phosphoprotein enriched in diabetes gene product (Ped/pea-15) regulates glucose metabolism and is increased in T2DM. Our novel data indicate that Ped/pea-15 mRNA expression and protein levels are significantly increased in omental adipose tissue (AT) from PCOS women compared to matched controls (p < 0.01); Ped/pea-15 levels in subcutaneous AT were not significantly different. Furthermore, Ped/pea-15 mRNA expression and protein levels were higher in omental compared to subcutaneous AT in PCOS subjects (p < 0.01); however, in control subjects, this was not significant. Glucose was predictive of omental AT Ped/pea-15 mRNA expression (p = 0.045). Importantly, glucose and insulin increased whereas metformin significantly decreased Ped/pea-15 levels in human omental AT explants. Our findings should serve to promote further research on Ped/pea-15 biology.

Healthcare staff perceptions towards influenza and potential COVID-19 vaccination in the 2020 pandemic context.

The COVID-19 pandemic generated renewed focus on infectious disease transmission in healthcare settings. This study aimed to evaluate staff perceptions towards influenza vaccination in the COVID-19 context. All healthcare workers within a major UK tertiary referral hospital were invited to answer a survey conducted from September 2nd to 13th, 2020. In all, 593 responses were received across a spectrum of roles; 44% reported they were more likely to get an influenza vaccine this year due to COVID-19; however, 10% felt that an influenza vaccine was less important due to social distancing. Additional questions evaluated intention to receive COVID-19 vaccination. There were substantial differences of opinion between staff groups.

Heat stress and PPE during COVID-19: impact on healthcare workers' performance, safety and well-being in NHS settings.

Personal protective equipment (PPE) can potentiate heat stress, which may have a negative impact on the wearer's performance, safety and well-being. In view of this, a survey was distributed to healthcare workers (HCWs) required to wear PPE during the coronavirus disease 2019 pandemic in the UK to evaluate perceived levels of heat stress and its consequences. Respondents reported experiencing several heat-related illness symptoms, and heat stress impaired both cognitive and physical performance. The majority of respondents stated that wearing PPE made their job more difficult. These, and additional, responses suggest that modification to current working practices is required urgently to improve the resilience of HCWs to wearing PPE during pandemics.

Audit of vaccination status of health-care workers who tested positive for SARS-CoV-2.

Multiple SARS-CoV-2 vaccinations have shown excellent efficacy during clinical trials. However, post vaccine surveillance is important to confirm 'real-world' findings of vaccine efficacy and safety. It is therefore imperative to identify individuals that become infected with SARS-CoV-2 post vaccination. We investigated the vaccination status of staff that had tested positive in a cohort of healthcare workers in one large tertiary hospital in the UK. At the time of the investigation, 8th December 2020 to 13th March 2021, 11,871 staff had been vaccinated and 225 staff tested positive for SARS-CoV-2. This period coincided with the second wave of SARS-CoV-2 infections in the UK which was driven by the Alpha variant. No healthcare workers who were double vaccinated had a positive PCR test for SARS-CoV-2 during this study period confirming vaccination with Pfizer BioNTec BNT162b2 gives excellent protection against infection of this variant.

Healthcare staff perceptions and misconceptions regarding antibody testing in the United Kingdom: implications for the next steps for antibody screening.

BACKGROUND: Healthcare workers have been at increased risk of exposure, infection and serious complications from COVID-19. Antibody testing has been used to identify staff members who have been previously infected by SARS-CoV-2, and has been rolled out rapidly in the United Kingdom. A number of comment and editorial articles have been published that raise concerns about antibody testing in this context. We present perceptions of National Health Service (NHS) healthcare workers in relation to SARS-CoV-2 antibody testing. METHODS: An electronic survey regarding perceptions towards SARS-CoV-2 antibody testing was distributed to all healthcare workers at a major NHS tertiary hospital following implementation of antibody testing. RESULTS: In total, 560 healthcare workers completed the survey (80% female; 25% of Black and Minority Ethnic background; 58% from frontline clinical staff). Exploring whether they previously had COVID-19 was the primary reported reason for choosing to undergo antibody testing (85.2%). In case of a positive antibody test, 72% reported that they would feel relieved, whilst 48% felt that they would be happier to work in a patient-facing area. Moreover, 12% responded that a positive test would mean "social distancing is less important", with 34% of the responders indicating that in this case they would be both less likely to catch COVID-19 and happier to visit friends/relatives. CONCLUSIONS: NHS staff members primarily seek out SARS-CoV-2 antibody testing for an appropriate reason. Based on our findings and given the lack of definite data regarding the extent of immunity protection from a positive SARS-CoV-2 antibody test, significant concerns may be raised regarding the reported interpretation by healthcare workers of positive antibody test results. This needs to be further explored and addressed to protect NHS staff and patients.

Risk factors for readmission of inpatients with diabetes: A systematic review.

AIM: We have limited understanding of which risk factors contribute to increased readmission rates amongst people discharged from hospital with diabetes. We aim to complete the first review of its kind, to identify, in a systematic way, known risk factors for hospital readmission amongst people with diabetes, in order to better understand this costly complication. METHOD: The review was prospectively registered in the PROSPERO database. Risk factors were identified through systematic review of literature in PubMed, EMBASE & SCOPUS databases, performed independently by two authors prior to data extraction, with quality assessment and semi-quantitative synthesis according to PRISMA guidelines. RESULTS: Eighty-three studies were selected for inclusion, predominantly from the United States, and utilising retrospective analysis of local or regional data sets. 76 distinct statistically significant risk factors were identified across 48 studies. The most commonly identified risk factors were; co-morbidity burden, age, race and insurance type. Few studies conducted power calculations; unstandardized effect sizes were calculated for the majority of statistically significant risk factors. CONCLUSION: This review is important in assessing the current state of the literature and in supporting development of interventions to reduce readmission risk. Furthermore, it provides an important foundation for development of rigorous, pre-specified risk prediction models.

Home administration of lanreotide Autogel by patients with acromegaly, or their partners, is safe and effective.

OBJECTIVE: The introduction of ready-to-use lanreotide Autogel has presented the possibility of patients receiving their acromegaly treatment at home. The objective of this study was to assess the ability of patients (or their partners) to administer repeat, unsupervised, injections of lanreotide Autogel without compromising efficacy or safety. DESIGN: Multicentre (10 UK regional endocrine centres), open-label, nonrandomised, controlled study. Patients elected either to receive/administer unsupervised home injections after injection technique training (Test group) or continued to receive injections from a healthcare professional (Control group). Patients received monthly injections of lanreotide Autogel at their established dose. Effects were monitored for up to 40 weeks. PATIENTS: Thirty patients (15 per treatment group) with acromegaly treated with a stable dose of lanreotide Autogel (60, 90 or 120 mg) for > or = 4 months before screening. Measurements The main outcome measure was the proportion of patients/partners who successfully administered injections throughout the study. RESULTS: All Test group patients/partners qualified to administer injections. Fourteen of 15 patients fulfilled all criteria for successful administration of unsupervised injections (95% confidence interval, 70%-99%). Fourteen of 15 Test and 14/15 Control patients maintained growth hormone and IGF-1 control. Local injection tolerability was good for both treatment groups, and safety profiles were similar. All Test group patients continued with unsupervised injections after the study. CONCLUSIONS: Patients with acromegaly or their partners were able to administer lanreotide Autogel injections with no detrimental effect on efficacy and safety; therefore, unsupervised home injections are a viable alternative to healthcare professional injections for suitably motivated patients.

Comparison of maternal ghrelin and leptin in healthy mothers and mothers with Type 1 diabetes.

AIMS: Maternal leptin affects placental growth hormone (GH), whereas ghrelin, a natural ligand of the growth-hormone-secretagogue receptor, modulates GH action. Both hormones may affect fetal growth, and dysregulation in diabetes may lead to fetal growth disturbances. The aim was to investigate changes in maternal ghrelin during pregnancy with diabetes and to establish reference leptin levels. METHODS: Twelve healthy non-diabetic (ND) and 12 pregnant women with Type 1 diabetes (T1DM) were recruited. Age and body mass index (BMI) [ND: age 29.9 +/- 4.7 years (mean +/- sd), BMI 25.2 +/- 3.7 kg/m2; T1DM: age 31 +/- 5.5 years, BMI 27 +/- 3.1 kg/m2] were similar in the groups. HbA1c in T1DM was 6.2 +/- 1.1% at 20 weeks, 6.3 +/- 1.1% at 30 weeks' gestation and 7.8 +/- 2.1% postpartum. Fasting plasma ghrelin, total leptin, free leptin (FL) and soluble leptin receptor (sOB-R) levels were measured at 20 and 30 weeks' gestation and postpartum and determined by radioimmunoassay. RESULTS: All pregnancies resulted in full-term singleton births with no differences in birth weight between groups [T1DM: 3.4 +/- 0.56 kg (mean +/- SE); ND: 3.6 +/- 0.3 kg, P = NS]. Ghrelin levels were lower in T1DM when corrected for age and mothers' weight (T1DM: 458 +/- 36 pg/ml and 432.9 +/- 26.6 pg/ml; ND: 562 +/- 52 pg/ml and 515.8 +/- 63 pg/ml at 20 and 30 weeks, respectively, P < 0.05). T1DM mothers had higher levels of sOB-R and FL levels declined at 30 weeks' gestation in T1DM (P = 0.04) but not in ND. CONCLUSION: In a population of pregnant women with expected changes in leptin levels as previously reported, ghrelin levels were lower in T1DM pregnancies at 20 and 30 weeks. This may have implications for fetal development and requires further study in diabetes, particularly in pregnancies that result in macrosomia.

Increased circulating levels of matrix metalloproteinase-2 and -9 in women with the polycystic ovary syndrome.

INTRODUCTION: Matrix metalloproteinases (MMPs) have been implicated in various pathological processes including inflammatory response, cardiovascular disease, and recently also in ovarian dysfunction. Polycystic ovary syndrome (PCOS) is the most common endocrinopathy in women of reproductive age and is characterized by chronic anovulation, insulin resistance, and increased prevalence of cardiovascular risk factors. Circulating levels of MMPs and their tissue inhibitors (TIMPs) so far have not been assessed in the PCOS. MATERIALS AND METHODS: Serum levels of MMP-2, MMP-9, TIMP-1, and TIMP-2 were measured in 23 women with PCOS [age (mean +/- sd), 30.5 +/- 6.7 yr; body mass index, 35.8 +/- 7.5 kg/m2] and 22 healthy, regularly menstruating women (age, 29.4 +/- 5.6; body mass index, 31.7 +/- 9.2 kg/m2). RESULTS: Women with PCOS had significantly higher concentrations of MMP-2 (999.8 +/- 155 vs. 521.8 +/- 242 ng/ml; P < 0.001), MMP-9 (592.4 +/- 279 vs. 345 +/- 309; P = 0.007), and TIMP-1 levels (823.8 +/- 145 vs. 692 +/- 210 ng/ml; P = 0.02) than control healthy women. There was no difference in TIMP-2 levels (47.3 +/- 30 vs. 44.4 +/- 39.7 ng/ml; P = 0.21) between women with PCOS and controls. CONCLUSIONS: Obese women with PCOS have elevated serum concentrations of MMP-2 and -9. It might be hypothesized that elevated MMP concentrations may be related to increased cardiovascular risk in PCOS and/or menstrual irregularities associated with this syndrome.

Reductions of circulating matrix metalloproteinase 2 and vascular endothelial growth factor levels after treatment with pegvisomant in subjects with acromegaly.

BACKGROUND: Vascular endothelial growth factor (VEGF) is involved in activation of the matrix metalloproteinase (MMP) system; the latter is implicated in atherosclerosis and cardiovascular disease. Patients with acromegaly have reduced life expectancy primarily due to cardiac disease. AIM: This study assessed plasma MMPs and VEGF levels in patients with active acromegaly (IGF-I > 130% upper limit of normal), and on treatment with pegvisomant. SUBJECTS AND METHODS: Twenty patients [nine female, mean age 56.1 +/- 13.8 yr (mean +/- sd)] were studied at baseline and on pegvisomant therapy and compared with data from 25 healthy volunteers (12 female; 56.6 +/- 14.2 yr). Plasma MMP-2, MMP-9, and VEGF levels were measured. RESULTS: Serum IGF-I fell from a baseline (mean +/- sd) level of 620.1 +/- 209.3 ng/ml to 237.5 +/- 118.5 ng/ml on pegvisomant (doses 10-60 mg; P < 0.001). MMP-2 levels at baseline were significantly higher in patients compared with healthy controls (380.7 +/- 204.8 vs. 207.4 +/- 62.6 ng/ml; P < 0.001), but with treatment a significant reduction in MMP-2 [380.7 +/- 204.8 vs. 203.0 +/- 77.4 ng/ml; P < 0.001] and VEGF (283.4 +/- 233.6 vs. 229.1 +/- 157.4 pg/ml; P = 0.008) was noted. There was no significant difference in MMP-9 levels between patients and controls at baseline (797.5 +/- 142.1 vs. 788.3 +/- 218.0 ng/ml; P = 0.87) or between baseline and posttreatment levels (797.5 +/- 142.1 vs. 780.0 +/- 214 ng/ml; P = 0.76). CONCLUSIONS: Our novel data demonstrate that treatment of acromegaly with pegvisomant leads to reductions in MMP-2 and VEGF concentrations. Further studies are required to determine the significance of these findings with relation to cardiac disease.

Effects of hormone replacement therapy type and route of administration on plasma matrix metalloproteinases and their tissue inhibitors in postmenopausal women.

BACKGROUND: Matrix metalloproteinases (MMPs) are implicated in numerous disease states including cardiovascular disease and cancer. Because recent studies have shown a detrimental effect of hormone replacement therapy on cardiovascular disease and breast cancer, we investigated whether there are any differences in the concentrations of MMPs and their tissue inhibitors (TIMPs) in women receiving various forms of postmenopausal therapy. MATERIAL AND METHODS: A total of 195 healthy postmenopausal women were assessed: 46 were taking tibolone, 47 were taking transdermal estradiol, 46 were taking conjugated equine estrogens (CEE), and 56 were not taking any menopausal therapy (CTR). Plasma levels of MMP-2 and -9 and TIMP-1 and TIMP-2 were measured by ELISA methods. RESULTS: MMP-9 levels were significantly higher in the CEE group in comparison with healthy women not receiving menopausal therapy (P < 0.05). In contrast, MMP-9 levels in the tibolone group were significantly lower than in any other group (P < 0.01, compared with transdermal estradiol and CTR, and P < 0.001, compared with CEE). MMP-9 to TIMP-1 ratio was also significantly higher in the CEE, compared with CTR (P < 0.05), and lower in the tibolone group (P < 0.01, compared with all groups). MMP-2 levels were higher in the CEE group, compared with healthy women not receiving any menopausal therapy, and women taking tibolone (P < 0.05). CONCLUSIONS: Our study demonstrates differential effects of various forms of postmenopausal therapy on serum levels of MMP-9 and MMP-2. It remains to be established whether these differences might be associated with differences in risks of cardiovascular disease and cancer in these women.

Orexin receptor expression in human adipose tissue: effects of orexin-A and orexin-B.

Orexin-A and orexin-B, via their receptors orexin-1 receptor (OX1R) and orexin-2 receptor (OX2R) have been shown to play a role in the regulation of feeding, body weight, and energy expenditure. Adipose tissue also contributes significantly to the maintenance of body weight by interacting with a complex array of bioactive peptides; however, there are no data as yet on the expression of orexin components in adipose tissue. We, therefore, analyzed the expression of OX1R and OX2R in human adipose tissue and determined functional responses to orexin-A and orexin-B. OX1R and OX2R mRNA expression was detected in subcutaneous (s.c.) and omental adipose tissue and in isolated adipocytes. Protein for OX1R and OX2R was also detected in whole adipose tissue sections and lysates. Treatment with orexin-A, and orexin-B (100 nM, 24 h) resulted in a significant increase in peroxisome proliferator-activated receptors gamma-2 mRNA expression in s.c. adipose tissue (P < 0.05). Hormone sensitive lipase mRNA was significantly reduced in omental adipose tissue with orexin-A and orexin-B treatment (P < 0.05). Glycerol release from omental adipose tissue was also significantly reduced with orexin-A treatment (P < 0.05). These findings demonstrate for the first time the presence of functional orexin receptors in human adipose tissue and suggest a role for orexins in adipose tissue metabolism and adipogenesis.

Novel placental expression of 2,3-bisphosphoglycerate mutase.

2,3-Bisphosphoglycerate mutase (2,3-BPGM), an erythroid-expressed enzyme, synthesises 2,3-bisphosphoglycerate (2,3-BPG), the allosteric modulator of haemoglobin. This ligand has a higher affinity for adult haemoglobin than for fetal haemoglobin and differential binding of it facilitates transfer of oxygen between adult and fetal blood by lowering the affinity of adult haemoglobin for oxygen. This paper reports the discovery that 2,3-BPGM is synthesised in non-erythroid cells of the human placenta. Western blot analysis of placental extracts revealed high levels of 2,3-BPGM in the human placenta. Immunohistochemical staining and in situ hybridisation experiments indicated that abundant 2,3-BPGM is present in the syncytiotrophoblast layer of the placental villi at the feto-maternal interface. A cytochemical staining technique showed that the placental 2,3-BPGM is active, indicating that 2,3-BPG is synthesised in the outermost cells of the placenta. These observations demonstrate an unexpected and abundant presence of an enzyme key to oxygen release from adult haemoglobin, at the interface between maternal and fetal circulations.

Cardiovascular risk management by blocking the endocannabinoid system.

The specific blockade of endocannabinoids at the level of the cannabinoid receptor 1 (CB (1) receptor) is a new therapeutic option to reduce body weight and manage cardiovascular risk. Although clinical trials are underway to document the safety and efficacy of this approach, much is still unknown about this endogenous system. Endocannabinoids and their receptors are expressed in the central nervous system as well as in the periphery and regulate the central neural circuits for food uptake and peripheral metabolic circuits. Within the context of food uptake, the stimulation of the CB (1) receptor with Delta (9)-tetrahydrocannabinol (Delta (9)-THC) enhances food consumption, while its blockade with receptor antagonists is an emerging relevant therapeutic means to reduce body weight. Rimonabant is the first of a new class of drugs that interferes with the endocannabinoid system by blocking the CB (1) receptor. In recent clinical studies, a substantial reduction in body weight and waist circumference was associated with an improvement of the cardiovascular risk profile. In particular, increased HDL cholesterol, decreased serum triglycerides and improved insulin sensitivity were observed. Further research will serve to establish the role of these compounds in cardiovascular risk management.