Explore the vast range of titles available.

Procalcitonin (PCT) is an acute-phase reactant with concentrations ≥0.5 μg/L indicative of possible bacterial infection in patients with SARS-CoV-2 infection (COVID-19). Some with severe COVID-19 develop cytokine storm secondary to virally driven hyper-inflammation. However, increased pro-inflammatory cytokines are also seen in bacterial sepsis. This study aimed to assess the clinical utility of a cytokine panel in the assessment of COVID-19 with bacterial superinfections along with PCT and C-reactive protein (CRP). The retrospective analysis included serum cytokines (interleukins; IL-1β, IL-6, IL-8 and tumour necrosis factor (TNFα)) measured using Ella™ (Bio-Techne, Oxford, UK) and PCT measured by Roche Cobas (Burgess Hill, UK) in patients admitted with COVID-19 between March 2020 and January 2021. Patients enrolled into COVID-19 clinical trials, treated with Remdesivir/IL-6 inhibitors were excluded. The cytokine data was compared between intensive care unit (ICU) patients, age matched non-ICU patients and healthy volunteers as well as ICU patients with high and normal PCT (≥0.5 vs. <0.5 μg/L). Cytokine concentrations and CRP were higher in COVID-19 patients (76; ICU & non-ICU) vs. healthy controls (n = 24), all p<0.0001. IL-6, IL-8, TNFα and were higher in ICU patients (n = 46) vs. non-ICU patients (n = 30) despite similar CRP. Among 46 ICU patients, the high PCT group (n = 26) had higher TNFα (p<0.01) and longer ICU stay (mean 47 vs. 25 days, p<0.05). There was no difference in CRP and blood/respiratory culture results between the groups. Pro-inflammatory cytokines and PCT were higher in COVID-19 patients requiring ICU admission vs. non-ICU admissions despite no difference in CRP. Furthermore, TNFα was higher in those with high PCT and requiring longer ICU admission despite no difference in CRP or rate of bacterial superinfection.

Introduction: Metabolic dysfunction–associated fatty liver disease (MAFLD) is highly prevalent among people living with severe obesity (body mass index [BMI] ≥ 35 kg/m 2 ). However, it remains unknown how sex and adipose tissue distribution are related to MAFLD onset and progression into metabolic dysfunction–associated steatohepatitis (MASH) or advanced stages of fibrosis. Methodology: We retrospectively studied patients with severe obesity who were eligible for bariatric surgery. Demographic characteristics, biomarkers, and cardiometabolic comorbidities were reported. Anthropometric indices such as BMI, waist circumference (WC), waist‐to‐hip ratio (WHR), waist‐to‐height ratio (WHtR), neck circumference (NC), lipid accumulation product (LAP), visceral adiposity index (VAI), body adiposity index (BAI), abdominal volume index (AVI), and body roundness index (BRI) were measured or calculated. MAFLD, MASH, and stages of fibrosis (F1‐F4) were established from perioperative liver biopsies. Standardized univariate and multivariate logistic regression analyses were used to examine the association between demographic variables, anthropometric indices, cardiometabolic conditions, and the risk of MASH or severe fibrosis (F2‐F4). Results: A total of 2091 participants with severe obesity were included in the analyses; BMI 47.9 ± 7.3 kg/m 2 , age 46.2 ± 11.2 years, and 68.4% females. Overall, MAFLD prevalence was 79.5%, with 44.5% having MASH and 24.4% having severe fibrosis (Stage 2 or higher). No anthropometric indices of adiposity were associated with MASH or fibrosis severity. In this population, female sex was a risk factor for severe fibrosis (OR: 1.27, 95% CI 1.01–1.59, p < 0.05). Conclusions: MAFLD and MASH are highly prevalent in individuals living with severe obesity, but no anthropometric indices or laboratory tests are good predictors of MAFLD or MASH in this population. When MAFLD is diagnosed, our results suggest that females with severe obesity might be at higher risk of advanced stages of fibrosis.

Background Sodium glucose co-transporter2 inhibitors reduce the incidence of cardiovascular events in patients with type 2 diabetes mellitus based on the results of recent cardiovascular outcome studies. Herein, we investigated the effects of long-term treatment with canagliflozin on biochemical and immunohistochemical markers related to atherosclerosis and atherosclerosis development in the aorta of apolipoprotein E knockout (Apo-E (−/−) ) mice. Methods At the age of 5 weeks, mice were switched from normal to a high-fat diet. After 5 weeks, Apo-E (−/−) mice were divided into control-group (6 mice) treated with 0.5% hydroxypropyl methylcellulose and Cana-group (7 mice) treated with canagliflozin (10 mg/kg per day) per os. After 5 weeks of intervention, animals were sacrificed, and heart and aorta were removed. Sections stained with hematoxylin–eosin (H&E) were used for histomorphometry whereas Masson’s stained tissues were used to quantify the collagen content. Immunohistochemistry to assess MCP-1, CD68, a-smooth muscle actin, MMP-2, MMP-9, TIMP-1 and TIMP-2 expression was carried out and q-PCR experiments were performed to quantify mRNA expression. Results Canagliflozin-group mice had lower total-cholesterol, triglycerides and glucose levels ( P  < 0.01), while heart rate was significantly lower (P < 0.05). Histomorphometry revealed that one in seven Cana-group mice versus four in six control mice developed atheromatosis, while aortic root plaque was significantly less, and collagen was 1.6 times more intense in canagliflozin-group suggesting increased plaque stability. Immunohistochemistry revealed that MCP-1 was significantly less expressed ( P  < 0.05) in the aortic root of canagliflozin-group while reduced expression of a-actin and CD68 was not reaching significance ( P  = 0.15). VCAM-1 and MCP-1 mRNA levels were lower ( P  = 0.02 and P  = 0.07, respectively), while TIMP-1/MMP-2 ratio expression was higher in canagliflozin-group approaching statistical significance ( P  = 0.07). Conclusions Canagliflozin attenuates the progression of atherosclerosis, reducing (1) hyperlipidemia and hyperglycemia, and (2) inflammatory process, by lowering the expression of inflammatory molecules such as MCP-1 and VCAM-1. Moreover, canagliflozin was found to increase the atherosclerotic plaque stability via increasing TIMP-1/MMP-2 ratio expression.

Polycystic ovary syndrome (PCOS) is the most common cause of anovulatory infertility. Obesity exacerbates the reproductive complications of PCOS; however, the management of obesity in women with PCOS remains a large unmet clinical need. Observational studies have indicated that bariatric surgery could improve the rates of ovulatory cycles and prospects of fertility; however, the efficacy of surgery on ovulation rates has not yet been compared with behavioural modifications and medical therapy in a randomised trial. The aim of this study was to compare the safety and efficacy of bariatric surgery versus medical care on ovulation rates in women with PCOS, obesity, and oligomenorrhoea or amenorrhoea. In this multicentre, open-label, randomised controlled trial, 80 women older than 18 years, with a diagnosis of PCOS based on the 2018 international evidence-based guidelines for assessing and managing PCOS, and a BMI of 35 kg/m2 or higher, were recruited from two specialist obesity management centres and via social media. Participants were randomly assigned at a 1:1 ratio to either vertical sleeve gastrectomy or behavioural interventions and medical therapy using a computer-generated random sequence (PLAN procedure in SAS) by an independent researcher not involved with any other aspect of the clinical trial. The median age of the entire cohort was 31 years and 79% of participants were White. The primary outcome was the number of biochemically confirmed ovulatory events over 52 weeks, and was assessed using weekly serum progesterone measurements. The primary endpoint included the intention-to-treat population and safety analyses were per-protocol population. This study is registered with the ISRCTN registry (ISRCTN16668711). Participants were recruited from Feb 20, 2020 to Feb 1, 2021. 40 participants were assigned to each group and there were seven dropouts in the medical group and ten dropouts in the surgical group. The median number of ovulations was 6 (IQR 3·5–10·0) in the surgical group and 2 (0·0–4·0) in the medical group. Women in the surgical group had 2.5 times more spontaneous ovulations compared with the medical group (incidence rate ratio 2·5 [95% CI 1·5–4·2], p<0·0007). There were more complications in the surgical group than the medical group, although without long-term sequelae. There were 24 (66·7%) adverse events in the surgical group and 12 (30·0%) in the medical group. There were no treatment-related deaths. Bariatric surgery was more effective than medical care for the induction of spontaneous ovulation in women with PCOS, obesity, and oligomenorrhoea or amenorrhoea. Bariatric surgery could, therefore, enhance the prospects of spontaneous fertility in this group of women. The Jon Moulton Charity Trust.

One anastomosis gastric bypass (OAGB) is a relatively novel bypass surgery variant, increasingly used as a primary surgical procedure. A total of 101 patients (mean age 44.7 ± 10.7 years, mean BMI 47.2 ± 6.6 kg/m2) underwent OAGB between 2014 and 2019 in a single institution. Results obtained 6,12 and 24 months postoperatively were compared with the pre-operative values using “Analyse-it software v5.40.2” and Graphpad Prism v9.3 for figures and tables. Data were tested for normality, described as Mean ± SD, compared using paired sample t-test with 5% p-value for significance and 95% confidence interval (CI). A significant body mass index (BMI), haemoglobin A1c (HbA1c) and low-density lipoprotein (LDL) reduction was recorded throughout follow-up period, with greatest improvement seen 2 years after surgery (47.6 ± 22 kg/m2 vs. 29.4 ± 6.4 kg/m2 ,6.7 ± 1.8% vs. 5.5 ± 0.2% and 3.2 ± 1 vs. 2.05 + 0.7 mmol/ l, p  < 0.05). The number of glucose-lowering drugs decreased from 1.6 ± 0.9 to 0.3 ± 0.4 at 24-months, p  < 0.001. The rates for zinc, ferritin, folate, B12 and vitamin D deficiency at 24-months were: 8.9%,4%, 5.9%, 0% and 3% respectively. OAGB can effectively downstage obesity disease and improve glucose and lipid homeostasis with a low risk for nutritional deficiencies. This study is one of few to report specifically on the frequency and type of nutritional deficiencies following OAGB surgery.

Prolactinomas represent the most common type of secretory pituitary neoplasms, with a therapeutic management that varies considerably based on tumour size and degree of hyperprolactinemia. The aim of the current study was to evaluate the relationship between serum prolactin (PRL) concentrations and prolactinoma size, and to determine a cut-off PRL value that could differentiate micro- from macro-prolactinomas. A retrospective cohort study of 114 patients diagnosed with prolactinomas between 2007 and 2017 was conducted. All patients underwent gadolinium enhanced pituitary MRI and receiver operating characteristic (ROC) analyses were performed. 51.8% of patients in this study were men, with a mean age at the time of diagnosis of 42.32 ± 15.04 years. 48.2% of the total cohort were found to have microadenomas. Baseline serum PRL concentrations were strongly correlated to tumour dimension (r = 0.750, p  = 0.001). When performing the ROC curve analysis, the area under the curve was 0.976, indicating an excellent accuracy of the diagnostic method. For a value of 204 μg/L (4338 mU/L), sensitivity and specificity were calculated at 0.932 and 0.891, respectively. When a cut off value of 204 μg/L (4338 mU/L) was used, specificity was 93.2%, and sensitivity 89.1%, acceptable to reliably differentiate between micro- and macro- adenomas.

Background Glucagon like peptide-1 receptor agonist (GLP-1RA) use in individuals with high atherosclerotic cardiovascular disease (ASCVD) risk reduces major adverse cardiovascular events (MACE). However, its clinical impact, in terms of numbers needed to treat (NNT), efficacy and safety profile in reducing the risk of myocardial infarction (MI) and the individual ASCVD constituents remain unclear. Methods Electronic databases, Medline and Embase were reviewed for randomized trials from inception to 29 May 2025. Risk-reduction effect of GLP-1RA were pooled using pairwise meta-analysis with random-effects model. The primary outcome was MI, and secondary outcomes were the individual ASCVD constituents. Results 109,846 patients from 25 unique studies were included. Over a follow-up duration of 3.48 ± 1.51 (1.55 to 5.47) years, GLP-1RA reduced the risk of total MI (RR: 0.86, p  < 0.01), with numbers needed to benefit (NNTB) of 207 to prevent one event of MI. Higher body mass index was associated with greater MI risk reduction (β: -0.09, p  = 0.03) in GLP-1RA users. GLP-1RA reduced cardiovascular mortality (RR: 0.87, p  < 0.01, NNTB 170), MACE (RR: 0.87, p  < 0.01, NNTB 67) and stroke (RR: 0.88, p  < 0.01, NNTB 335) compared to placebo. GLP-1RA commonly resulted in gastrointestinal side-effects amongst other systems (RR: 1.55, p  < 0.01, NNTH 9). Conclusion GLP-1RA reduced the risk of MI, stroke, cardiovascular mortality and MACE in a broad range of patients with and without T2DM and/or prior ASCVD, supporting its role in ASCVD prevention, especially in the cohort with high BMI. Trial registration : Open Science Framework ( https://doi.org/10.17605/OSF.IO/7VXN5 ). Graphical Abstract

AimsPublic Health England has identified that in COVID-19, death rates among ethnic minorities far exceeds that of the white population. While the increase in ethnic minorities is likely to be multifactorial, to date, no studies have looked to see whether values for routine clinical biochemistry parameters differ between ethnic minority and white individuals.MethodsBaseline biochemical data for 22 common tests from 311 SARS-CoV-2 positive patients presenting to hospital in April 2020 in whom ethnicity data were available was retrospectively collected and evaluated. Data comparisons between ethnic minority and white groups were made for all patient data and for the subset of patients subsequently admitted to intensive care.ResultsWhen all patient data were considered, the ethnic minority population had statistically significant higher concentrations of C reactive protein (CRP), aspartate aminotransferase and gamma-glutamyl transferase, while troponin T was higher in the white group. A greater proportion of ethnic minority patients were subsequently admitted to intensive care, but when the presenting biochemistry of this subset of patients was compared, no significant differences were observed between ethnic minority and white groups.ConclusionOur data show for the first time that routine biochemistry at hospital presentation in COVID-19 differs between ethnic minority and white groups. Among the markers identified, CRP was significantly higher in the ethnic minority group pointing towards an increased tendency for severe inflammation in this group.

Although most of the current evidence on myocardial infarction focuses on obesity, there is growing evidence that patients who are underweight have unfavorable prognosis. This study aimed to explore the prevalence, clinical characteristics, and prognosis of this population at risk. Embase and Medline were searched for studies reporting outcomes in populations who were underweight with myocardial infarction. Underweight and normal weight were defined according to the World Health Organization criteria. A single-arm meta-analysis of proportions was used to estimate the prevalence of underweight in patients with myocardial infarction, whereas a meta-analysis of proportions was used to estimate the odds ratio of all-cause mortality, medications prescribed, and cardiovascular outcomes. Twenty-one studies involving 6,368,225 patients were included, of whom 47,866 were underweight. The prevalence of underweight in patients with myocardial infarction was 2.96% (95% confidence interval 1.96% to 4.47%). Despite having fewer classical cardiovascular risk factors, patients who were underweight had 66% greater hazard for mortality (hazard ratio 1.66, 95% confidence interval 1.44 to 1.92, p <0.0001). The mortality of patients who were underweight increased from 14.1% at 30 days to 52.6% at 5 years. Nevertheless, they were less likely to receive guideline-directed medical therapy. Relative to subjects with normal weight, Asian populations who were underweight had greater mortality risks than those of their Caucasian counterparts (p = 0.0062). In conclusion, in patients with myocardial infarction, those who were underweight tend to have poorer prognostic outcomes. A lower body mass index is an independent predictor of mortality, which calls for global efforts in addressing this modifiable risk factor in clinical practice guidelines.

Patient response after treatment of renal cell cancer (RCC) with systemic agents, which include various drug categories, is generally poor and unpredictable. In this context, the ideal drug administration includes tools to predict the sensitivity of the disease to therapy. The aim of this study was to systematically summarize the reports on the predictive value of the methylation status in the systemic therapy of RCC. Only original articles reporting on the association of promoter methylation with the response of patients or cell lines to systemic agents were included in this review. We applied PRISMA recommendations to the structure and methodology of this systematic review. Our literature search concluded with 31 articles conducted on RCC cell lines and patient tissues. The majority of the studies demonstrated a methylation-dependent response to systemic agents. This correlation suggests that the methylation pattern can be used as a predictive tool in the management of RCC with various classes of systemic agents. However, although methylation biomarkers show promise for predicting response, the evidence of such correlation is still weak. More studies on the gene methylation pattern in patients under systemic therapy and its correlation with different degrees of response are needed.