The Effect of Sargassum fusiforme and Fucus vesiculosus on Continuous Glucose Levels in Overweight Patients with Type 2 Diabetes Mellitus: A Feasibility Randomized, Double-Blind, Placebo-Controlled Trial.

BACKGROUND: Brown seaweed is promising for the treatment of type 2 diabetes mellitus (T2DM). Its bioactive constituents can positively affect plasma glucose homeostasis in healthy humans. We investigated the effect of the brown seaweeds Sargassum (S.) fusiforme and Fucus (F.) vesiculosus in their natural form on glucose regulation in patients with T2DM. METHODS: We conducted a randomized, double-blind, placebo-controlled pilot trial. Thirty-six participants with T2DM received, on a daily basis, either 5 g of dried S. fusiforme, 5 g of dried F. vesiculosus, or 0.5 g of dried Porphyra (control) for 5 weeks, alongside regular treatment. The primary outcome was the between-group difference in the change in weekly average blood glucose levels (continuous glucose monitoring). The secondary outcomes were the changes in anthropometrics, plasma lipid levels, and dietary intake. The data were analyzed using a linear mixed-effects model. RESULTS: The change in weekly average glucose levels was 8.2 ± 2.1 to 9.0 ± 0.7 mmol/L (p = 0.2) in the S. fusiforme group (n = 12) and 10.1 ± 3.3 to 9.2 ± 0.7 mmol/L (p = 0.9) in the F. vesiculosus group (n = 10). The between-group difference was non-significant. Similarly, no between-group differences were observed for the changes in the secondary outcomes. DISCUSSION: A daily intake of 5 g of fresh, dried S. fusiforme or F. vesiculosus alongside regular treatment had no differential effect on weekly average blood glucose levels in T2DM.

Metabolic dysfunction-associated steatotic liver disease and the heart.

The prevalence and severity of metabolic dysfunction-associated steatotic liver disease (MASLD) are increasing. Physicians who treat patients with MASLD may acknowledge the strong coincidence with cardiometabolic disease, including atherosclerotic cardiovascular disease (asCVD). This raises questions on co-occurrence, causality, and the need for screening and multidisciplinary care for MASLD in patients with asCVD, and vice versa. Here, we review the interrelations of MASLD and heart disease and formulate answers to these matters. Epidemiological studies scoring proxies for atherosclerosis and actual cardiovascular events indicate increased atherosclerosis in patients with MASLD, yet no increased risk of asCVD mortality. MASLD and asCVD share common drivers: obesity, insulin resistance and type 2 diabetes mellitus (T2DM), smoking, hypertension, and sleep apnea syndrome. In addition, Mendelian randomization studies support that MASLD may cause atherosclerosis through mixed hyperlipidemia, while such evidence is lacking for liver-derived procoagulant factors. In the more advanced fibrotic stages, MASLD may contribute to heart failure with preserved ejection fraction by reduced filling of the right ventricle, which may induce fatigue upon exertion, often mentioned by patients with MASLD. Some evidence points to an association between MASLD and cardiac arrhythmias. Regarding treatment and given the strong co-occurrence of MASLD and asCVD, pharmacotherapy in development for advanced stages of MASLD would ideally also reduce cardiovascular events, as has been demonstrated for T2DM treatments. Given the common drivers, potential causal factors and especially given the increased rate of cardiovascular events, comprehensive cardiometabolic risk management is warranted in patients with MASLD, preferably in a multidisciplinary approach.

A global survey of health care workers' awareness of non-alcoholic fatty liver disease: The AwareNASH survey.

BACKGROUND: The estimated global prevalence and burden of non-alcoholic fatty liver disease (NAFLD) and its advanced stage, non-alcoholic steatohepatitis (NASH), is increasing. Yet, NAFLD remains largely underdiagnosed. In addition to hepatic morbidity and mortality, NAFLD is associated with increased cardiovascular complications, warranting a multidisciplinary approach. Despite its rapidly increasing prevalence, knowledge of NAFLD among healthcare workers is limited, especially with specialists outside the field of hepatology and gastroenterology. OBJECTIVES: To investigate knowledge, practice and opinions/attitudes of healthcare workers towards diagnosis and management of NAFLD/NASH. METHODS: The survey was designed in collaboration with a multidisciplinary scientific committee established especially for this study. The survey was disseminated to healthcare workers from seven different disciplines through four collaborating societies, social media and at a cardiology-themed conference from February to June 2022. Median and interquartile range were mentioned for numeric responses and proportions for categorical responses or responses on a Likert scale. Likert scale responses were treated as ordinal data and analysed with the appropriate tests. RESULTS: The full dataset included 613 respondents from 88 different countries (including 488 physicians). 64% of the surveyed physicians underestimated the prevalence of NAFLD. General practitioners and cardiologists underestimated the prevalence most often (74% and 77%, respectively). Compared to the other disciplines, cardiologists were least familiar with the symptoms and diagnostic criteria and felt least confident in diagnosing and managing NAFLD. Overall, 65% of physicians reported regularly using evidence-based guidelines for managing NAFLD, yet 72% reported challenges in providing lifestyle recommendations. A lack of awareness was the most common reported reason for the lack of screening for NAFLD (68% respectively). CONCLUSIONS: Despite the growing burden of NAFLD, there is a significant gap in awareness, knowledge, and management among physicians treating patients with cardiometabolic comorbidities, particularly cardiologists. Hepatologists and gastroenterologists could play a role in educating their fellow physicians.

Effect of bariatric surgery on NAFLD/NASH: a single-centre observational prospective cohort study.

INTRODUCTION: The prevalence of non-alcoholic fatty liver disease (NAFLD) ranges from 25% in the general population to 90% in patients with obesity scheduled for bariatric surgery. NAFLD can progress towards non-alcoholic steatohepatitis (NASH) associated with complications such as cirrhosis, hepatocellular carcinoma and cardiovascular disease. To date, losing weight and lifestyle modifications are the best known treatments for NASH. Bariatric surgery significantly improves NAFLD/NASH in the short term. However, the extent of this improvement is not yet clear and long-term data on the natural course of NAFLD/NASH after bariatric surgery are lacking. The factors involved in NAFLD/NASH regression after bariatric surgery have not been elucidated. METHODS AND ANALYSIS: This is an observational prospective cohort study including patients scheduled for bariatric surgery. Extensive metabolic and cardiovascular analyses will be carried out including measurements of carotid intima media thickness and pulse wave velocity. Genomic, proteomic, lipidomic and metabolomic studies will be done. Microbioma analyses before and 1 year after surgery will be done. Transient elastography measurements will be performed before and at 1, 3 and 5 years after surgery. For those with an elevated preoperative transient elastography measurement by Fibroscan, a laparoscopic liver biopsy will be performed during surgery. Primary outcome measures are the change of steatosis and liver fibrosis 5 years after surgery. Secondary outcome measure is the comparison of the transient elastography measurements with the NAFLD Activity Score from the biopsies. ETHICS AND DISSEMINATION: The protocol has been approved by the Medical Research Ethics Committees United, Nieuwegein, on 1 March 2022 (registration code R21.103/NL79423.100.21). The study results will be submitted for publication in peer-reviewed journals and data will be presented at scientific meetings. TRIAL REGISTRATION NUMBER: NCT05499949.

Historical Lattice Trees.

We prove that the rescaled historical processes associated to critical spread-out lattice trees in dimensions d>8 converge to historical Brownian motion. This is a functional limit theorem for measure-valued processes that encodes the genealogical structure of the underlying random trees. Our results are applied elsewhere to prove that random walks on lattice trees, appropriately rescaled, converge to Brownian motion on super-Brownian motion.

Detection of reassortant influenza B strains from 2004 to 2015 seasons in Barcelona (Catalonia, Spain) by whole genome sequencing.

BACKGROUND: Influenza B viruses (FLUBV) have segmented genomes which enables the virus to evolve by segment reassortment. Since the divergence of both FLUBV lineages, B/Victoria/2/87 (FLUBV/VIC) and B/Yamagata/16/88 (FLUBV/YAM), PB2, PB1 and HA have kept the same ancestor, while some reassortment events in the other segments have been reported worldwide. The aim of the present study was to find out reassortment episodes in FLUBV strains detected in cases attended at Hospital Universitari Vall d'Hebron and Hospital de la Santa Creu i Sant Pau (Barcelona, Spain) from 2004 to 2015 seasons. METHODS: From October 2004 to May 2015, respiratory specimens were received from patients with respiratory tract infection suspicion. Influenza detection was carried out by either cell culture isolation, immunofluorescence or PCR-based assays. A RT-PCR was performed to distinguish both lineages by agarose gel electrophoresis. Whole genome amplification was performed using the universal primer set by Zhou et al. in 2012, and subsequently sequenced using Roche 454 GS Junior platform. Bioinformatic analysis was performed to characterise the sequences with B/Malaysia/2506/2007 and B/Florida/4/2006 corresponding sequences as reference of (B/VIC) and (B/YAM), respectively. RESULTS: A total of 118 FLUBV (75 FLUBV/VIC and 43 FLUBV/YAM), from 2004 to 2006, 2008-2011 and 2012-2015 seasons, were studied. The whole genome of 58 FLUBV/VIC and 42 FLUBV/YAM viruses was successfully amplified. Based on HA sequences, most FLUBV/VIC viruses (37; 64%) belonged to clade 1A (B/Brisbane/60/2008) except to 11 (19%), which fell within clade 1B (B/HongKong/514/2009) and 10 (17%) to B/Malaysia/2506/2004. Nine (20%) FLUBV/YAM viruses belonged to clade 2 (B/Massachusetts/02/2012), 18 (42%) to clade 3 (B/Phuket/3073/2013) and 15 (38%) fell within Florida/4/2006. Numerous intra-lineage reassortments in PB2, PB1, NA and NS were found in 2 2010-2011 viruses. An important inter-lineage reassortment event from 2008 to 2009 (11), 2010-2011 (26) and 2012-2013 (3) FLUBV/VIC (clade 1) strains to FLUBV/YAM (clade 3) was found, in addition to 1 reassortant NS in 2010-2011 B/VIC virus. CONCLUSIONS: Intra- and inter-lineage reassortment episodes were revealed by WGS. While PB2-PB1-HA remained in complex, NP and NS reassortant viruses were found in both lineages. Despite reassorment events are not often, the characterisation only by HA and NA sequences might be underestimating their detection.

Establishing a Multicenter Network for Patients With Thyroid Nodules and Cancer: Effects on Referral Patterns.

OBJECTIVE: To perform a qualitative evaluation of the Thyroid Network, with a quantitative analysis of second opinion referrals for patients in the southwestern part of the Netherlands who have thyroid nodules and cancer. METHODS: This prospective observational study registered all patients with thyroid nodules and cancer who were referred to the academic hospital from 2 years before and 4 years after the foundation of the Thyroid Network. We implemented biweekly regional multidisciplinary tumor boards using video conference and a regional patient care pathway for patients with thyroid nodules and cancer. For qualitative evaluation, interviews were conducted with a broad selection of stakeholders via maximum variation sampling. The primary outcome was the change in second opinions after the foundation of the Thyroid Network. RESULTS: Second opinions from Thyroid Network hospitals to the academic hospital decreased from 10 (30%) to 2 (7%) two years after the start of the Thyroid Network (P = .001), while patient referrals remained stable (n = 108 to 106). Qualitative evaluation indicated that the uniform care pathway and the regional multidisciplinary tumor board were valued high. DISCUSSION: Establishing a regional network, including multidisciplinary tumor boards and a care pathway for patients with thyroid nodules and cancer, resulted in a decrease in second opinions of in-network hospitals and high satisfaction of participating specialists. IMPLICATIONS FOR PRACTICE: The concept of the Thyroid Network could spread to other regions as well as to other specialties in health care. Future steps would be to assess the effect of regional collaboration on quality of care and patient satisfaction.

Molecular characterization and clinical impact of human bocavirus at a tertiary hospital in Barcelona (Catalonia, Spain) during the 2014-2017 seasons.

PURPOSE: The aim was to describe the prevalence, molecular epidemiology and clinical manifestations of human bocavirus (HBoV) in patients attended at a tertiary hospital in Barcelona, Spain. METHODS: From October 2014 to May 2017, respiratory specimens from paediatric patients were collected for respiratory viruses' laboratory-confirmation. Phylogenetic analyses from partial VP1 sequences were performed from all HBoV laboratory-confirmed specimens. Clinical features were retrospectively studied. RESULTS: 178/10271 cases were HBoV laboratory-confirmed. The median age was 1.53 (IQR 1.0-2.3). Co-detection was highly reported (136; 76%). All viruses belonged into HBoV1 genotype but one into HBoV2. Non-reported mutations were observed and two sites were suggestive to be under negative selection. 61% (109/178) cases had lower RTI (LRTI), of whom 84 had co-detections (77%) and 76 had comorbidities (70%). LRTI was the cause of hospitalization in 85 out of 109 cases (78%), and no differences were found regarding severity factors during hospitalization between co- and single-detections, except for median length of respiratory support, which was longer in cases with co-detections. CONCLUSIONS: Close monitoring of predominant HBoV1 showed a high similarity between viruses. The presence of comorbidities might explain the high prevalence of LRTI. Symptomatology in HBoV single-detected cases suggest that HBoV is a true pathogen.

Normalization of Cardiac Function After Bariatric Surgery Is Related to Autonomic Function and Vitamin D.

PURPOSE: Subclinical cardiac dysfunction is common in patients with obesity. Bariatric surgery is associated with normalization of subclinical cardiac function in 50% of the patients with obesity. The aim of this study was to identify predictors for a lack of improvement of subclinical cardiac dysfunction 1-year post-bariatric surgery. METHODS: Patients who were referred for bariatric surgery were enrolled in a longitudinal study. Inclusion criteria were age 35-65 years and BMI ≥ 35 kg/m2. Patients with a suspicion of or known cardiovascular disease were excluded. Conventional and advanced echocardiography, Holter monitoring, and blood tests were performed pre- and 1-year post-bariatric surgery. Subclinical cardiac dysfunction was defined as either a reduced left ventricular ejection fraction, decreased global longitudinal strain (GLS), diastolic dysfunction, arrhythmia, or an increased BNP or hs Troponin I. RESULTS: A total of 99 patients were included of whom 59 patients had cardiac dysfunction at baseline. Seventy-two patients completed the 1-year follow-up after bariatric surgery. There was a significant reduction in weight and cardiovascular risk factors. Parameters of cardiac function, such as GLS, improved. However, in 20 patients cardiac dysfunction persisted. Multivariate analysis identified a decreased heart rate variability (which is a measure of autonomic function), and a decreased vitamin D pre-surgery as predictors for subclinical cardiac dysfunction after bariatric surgery. CONCLUSION: Although there was an overall improvement of cardiac function 1-year post-bariatric surgery, autonomic dysfunction and a decreased vitamin D pre-bariatric surgery were predictors for a lack of improvement of subclinical cardiac dysfunction.

Improvement of non-invasive tests of liver steatosis and fibrosis as indicators for non-alcoholic fatty liver disease in type 2 diabetes mellitus patients with elevated cardiovascular risk profile using the PPAR-α/γ agonist aleglitazar.

BACKGROUND: Peroxisome proliferator-activated receptor (PPAR) agonists may have favorable outcomes on non-alcoholic fatty liver disease. This study serves as proof of concept to evaluate whether dual PPAR-α/γ agonists improve non-invasive tests of liver steatosis and fibrosis. METHODS: This is a post-hoc analysis of a randomized, double-blind, placebo-controlled, multi-center trial comprising 7226 patients with type 2 diabetes mellitus and recent coronary artery disease randomized to receive aleglitazar, a PPAR-α/γ agonists, or placebo for two years. Main outcomes were change in non-invasive tests for liver steatosis and fibrosis: Liver Fat Score (LFS), Liver Accumulation Product (LAP), Fibrosis-4 (FIB-4), and NAFLD Fibrosis Score (NFS). RESULTS: LFS, LAP and FIB-4 decreased upon treatment, whereas scores in the placebo group remained the same or increased (P<0.001). NFS responded differently but remained consistently lower than placebo. In the treatment group more participants shifted to a lower FIB-4 and NFS category, or improved in respect to the LAP cut-off values compared to the placebo group (P<0.001 for FIB-4 and LAP, P<0.004 for NFS). LFS had a low discriminative power in this study. CONCLUSION: This post-hoc analysis showed improvement of non-invasive tests of liver steatosis and fibrosis after starting dual PPAR-α/γ agonist treatment, adding to the evidence that this pathway has potential in non-alcoholic fatty liver disease treatment.

Evaluation of nonalcoholic fatty liver disease (NAFLD) in severe obesity using noninvasive tests and imaging techniques.

The prevalence of nonalcoholic fatty liver disease (NAFLD) and the more severe and inflammatory type, nonalcoholic steatohepatitis (NASH), is increasing rapidly. Especially in high-risk patients, that is those with obesity, metabolic syndrome, and type 2 diabetes mellitus, the prevalence of NAFLD can be as high as 80% while NASH may be present in 20% of these subjects. With the worldwide increase of obesity, it is most likely that these numbers will rise. Since advanced stages of NAFLD and NASH are strongly associated with morbidity and mortality-in particular, cardiovascular disease, liver cirrhosis, and hepatocellular carcinoma-it is of great importance to identify subjects at risk. A great variety of noninvasive tests has been published to diagnose NAFLD and NASH, especially using blood- and imaging-based tests. Liver biopsy remains the gold standard for NAFLD/NASH. This review aims to summarize the different mechanisms leading to NASH and liver fibrosis, the different noninvasive liver tests to diagnose and evaluate patients with severe obesity.

Effects of dapagliflozin on postprandial lipid metabolism in type 2 diabetes mellitus.

Objectives: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) modulate lipid metabolism and improve cardiovascular morbidity and mortality in patients with type 2 diabetes mellitus (T2DM). The exact cardioprotective mechanism of SGLT2i is unclear. We evaluated the effects of SGLT2i on postprandial lipids, lipoprotein concentrations, glucose and fatty acids. Design: A placebo-controlled randomized, proof-of-concept study. Methods: Fourteen male patients with T2DM on intensive insulin regimen were randomly and double-blind allocated to 12 weeks dapagliflozin (10 mg) or placebo. Postprandial effects were assessed with an 8-h standardized oral fat loading test. Results: Mean glycated A1c did not change by dapagliflozin, but the mean daily insulin dose was significantly reduced. Although dapagliflozin did not affect fasting or postprandial levels of glucose and insulin, it increased the postprandial levels of glucagon. While fasting levels of free fatty acids and beta-hydroxybutyrate (bHBA) were unchanged, dapagliflozin significantly increased the postprandial bHBA response. This was seen in the context of increased postprandial glucagon levels by dapagliflozin, without influencing postprandial insulin or glucose levels. Dapagliflozin did not affect fasting or postprandial plasma cholesterol and triglycerides nor postprandial inflammatory markers. Fasting apolipoprotein B48 was decreased without affecting the postprandial response. Markers of inflammation and vascular function did not change. Conclusion: Treatment with dapagliflozin of patients with T2DM led to a reduction of fasting chylomicron remnants and increased postprandial ketone bodies compared to placebo suggesting enhanced hepatic fatty acid oxidation. The latter may have been caused by decreasing the insulin-glucagon ratio. The beneficial clinical effects seen in the trials using dapagliflozin most likely are not due to effects on postprandial inflammation nor postprandial lipemia.

Ridge preservation in molar sites comparing xenograft versus mineralized freeze-dried bone allograft: A randomized clinical trial.

OBJECTIVES: The main objective of the study was to compare the dimensional ridge changes and the histological composition after the use of an allograft or xenograft and a resorbable membrane in ridge preservation in molar sites and to evaluate the influence of bone plate thickness on dimensional changes and the need of lateral sinus augmentation following ridge preservation. MATERIALS AND METHODS: Twenty-four patients in need of maxillary or mandibular first or second molar extraction and subsequent implant placement were included and randomly assigned to a group; allograft or xenograft, plus a collagen membrane. Cone-beam computed tomographies were obtained after molar extraction and after 5 months. A bone sample was harvested at the time of implant placement and analyzed by histomorphometry. RESULTS: Bone ridge was reduced significantly. Major changes in width occurred at 1 mm from the bone crest (-2.93 ± 2.28 mm) (p = .0002), while in height, the greatest reduction occurred at the buccal area (-1.97 ± 2.21 mm) (p = .0006). However, differences between groups were not significant. Thicker buccal bone plates exhibited less bone remodeling, while histologically, both biomaterials resulted in similar tissue composition. The resulting available bone height in the implant site measured 7.30 ± 3.53 mm initially and 6.8 ± 3.61 mm after 5 months which allowed implant placement without the need for lateral sinus augmentation in all cases. Still, 55% of the preserved areas needed transcrestal sinus lift. CONCLUSION: Ridge preservation in molar sites using a mineralized allograft or xenograft provides similar dimensional and histomorphometrical results after 5 months.

Cardiovascular Biomarker Profiles in Obesity and Relation to Normalization of Subclinical Cardiac Dysfunction after Bariatric Surgery.

AIMS: We aimed to gain insight into the underlying pathophysiology of cardiac dysfunction in obesity patients and the improvement of cardiac function after weight loss. METHODS: This is a longitudinal study in which 92 cardiovascular biomarkers were measured by multiplex immunoassays in obesity patients without known cardiovascular disease, before and one year after bariatric surgery. RESULTS: Out of 100 eligible patients, 72 patients completed the follow-up. A total of 72 (78%) biomarkers changed significantly. The biomarkers with the highest relative changes represented processes linked mainly to insulin resistance and inflammation. In the patients with persistent subclinical cardiac dysfunction, the baseline values of 10 biomarkers were different from values in patients with normalization of cardiac function. Most of these biomarkers were linked to inflammation or atherosclerosis. Finally, a model was developed to investigate the relationship between changes in the biomarkers and persistent subclinical cardiac dysfunction. Seven biomarkers were retained in this model, mainly linked to inflammation, atherosclerosis, and hypercoagulability. CONCLUSION: The majority (78%) of cardiovascular biomarkers changed, pointing mainly to modulation of insulin resistance and inflammation. The baseline levels of 10 biomarkers, as well as pre- to post-bariatric surgery changes in seven biomarkers, were related to persistent subclinical cardiac dysfunction after bariatric surgery.

Cost-Effectiveness of Lower Extremity Nerve Decompression Surgery in the Prevention of Ulcers and Amputations: A Markov Analysis.

BACKGROUND: The costs and health effects associated with lower extremity complications in diabetes mellitus are an increasing burden to society. In selected patients, lower extremity nerve decompression is able to reduce symptoms of neuropathy and the concomitant risks of diabetic foot ulcers and amputations. To estimate the health and economic effects of this type of surgery, the cost-effectiveness of this intervention compared to current nonsurgical care was studied. METHODS: To estimate the incremental cost-effectiveness of lower extremity nerve decompression over a 10-year period, a Markov model was developed to simulate the onset and progression of diabetic foot disease in patients with diabetes and neuropathy who underwent lower extremity nerve decompression surgery, compared to a group undergoing current nonsurgical care. Mean survival time, health-related quality of life, presence or risk of lower extremity complications, and in-hospital costs were the outcome measures assessed. Data from the Rotterdam Diabetic Foot Study were used as current care, complemented with information from international studies on the epidemiology of diabetic foot disease, resource use, and costs, to feed the model. RESULTS: Lower extremity nerve decompression surgery resulted in improved life expectancy (88,369.5 life-years versus 86,513.6 life-years), gain of quality-adjusted life-years (67,652.5 versus 64,082.3), and reduced incidence of foot complications compared to current care (490 versus 1087). The incremental cost-effectiveness analysis was -€59,279.6 per quality-adjusted life-year gained, which is below the Dutch critical threshold of less than €80,000 per quality-adjusted life-year. CONCLUSIONS: Decompression surgery of lower extremity nerves improves survival, reduces diabetic foot complications, and is cost saving and cost-effective compared with current care, suggesting considerable socioeconomic benefit for society.

Biomarker profiles in obesity patients and their relation to cardiac dysfunction.

Aim: Current knowledge on the role of obesity in causing cardiac dysfunction is insufficient. Several biomarkers reflecting biological processes that may play a role in the occurrence of cardiac dysfunction in obesity patients are available. Purpose: To compare cardiovascular biomarker profiles between obesity patients and nonobese controls, and between obesity patients with and without cardiac dysfunction, in order to better understand the underlying pathophysiology of cardiac dysfunction in obesity patients. Materials & methods: Blood samples were obtained from 100 obesity patients (BMI ≥35 kg/m2) without known cardiovascular disease, and from 50 age- and gender-matched nonobese controls (BMI ≤30 kg/m2). The third cardiovascular panel of the Olink Multiplex platform was used for the measurement of 92 biomarkers. Results: The majority (53%) of biomarkers were elevated in obesity patients compared with nonobese controls. Only 5% of the biomarkers were elevated in obesity patients with cardiac dysfunction compared with those without. Biomarkers discriminating cardiac dysfunction from no cardiac dysfunction in obesity patients differed from those discriminating obese from nonobese patients. An elastic net model for the prediction of cardiac dysfunction in obesity patients had a high area under the receiver operating curve of 0.87 (95% CI: 0.79-0.94; p < 0.001). The sensitivity of this model was 84% and the specificity was 79%. Conclusion: A multiplex immunoassay was used for the first time in obesity patients without known cardiovascular disease. These patients have cardiovascular biomarker profiles that are clearly different from nonobese controls. Comparison of obesity patients with and without cardiac dysfunction suggested an important role for inflammation, atherosclerosis and insulin resistance in the underlying pathophysiology of cardiac dysfunction in obesity patients.

A new application of the Rotterdam Diabetic Foot Study Test Battery: grading pedal sensory loss to predict the risk of foot ulceration.

AIMS: To assess the relationship between the degree of loss of foot sensation at baseline and incidence of foot ulceration (DFU). METHODS: Diabetic patients (n = 416) participating in the observational Rotterdam Diabetic Foot (RDF) Study were followed prospectively (median 955.5 days (IQR, 841.5-1121)). Subjects underwent sensory testing of the feet (39-item RDF Study Test Battery) at baseline and were assessed regarding incident DFU. Seven groups of incremental degree of sensory loss were distinguished, according to the RDF-39 sum score. Kaplan-Meier and regression analyses were used to determine the independent hazard of baseline variables for new DFU. RESULTS: 40 participants developed DFUs. The mean incident rate of new-onset ulceration from study start was 4.5 (95%CI: 3.3 to 6.1) per 100 person-years, which increased significantly from 0 to 67.70 in the seven groups (p < 0.0005). Predictors for DFUs were higher RDF-39 score (aHR: 1.173, p < 0.0005) and kidney function (aHR: 1.022, p = 0.016). Prior DFU suggests increased mortality risk. CONCLUSIONS: The degree of sensory loss at baseline was associated with progression to DFU during follow-up. Grading the loss of sensation using the RDF Study Test Battery may result in a more precise risk stratification compared to the use of the 10 g monofilament according to current guidelines.

Analyses of abdominal adiposity and metabolic syndrome as risk factors for respiratory distress in COVID-19.

BACKGROUND: Several characteristics of the metabolic syndrome, such as obesity and hypertension, have emerged as risk factors for a poor clinical outcome in COVID-19. However, most reports lack data on the metabolic syndrome itself. This study investigated prospectively the relationship between respiratory deterioration and the presence of metabolic syndrome or abdominal adiposity in patients with COVID-19. METHODS: A prospective observational cohort study analysing patients with respiratory symptoms who presented at a local emergency department in the Netherlands. The influence of abdominal adiposity-assessed by an increased waist-hip ratio-and metabolic syndrome on respiratory deterioration and the length of hospital stay were analysed with multivariable logistic regressions and Kaplan-Meier analyses. RESULTS: In total, 166 patients were analysed, of whom 86 (52%) tested positive for COVID-19. The prevalence of metabolic syndrome did not differ between patients with COVID-19 with and without the need for intubation or level of supportive care (37.5% vs 48.4%, p=0.338). In contrast, abdominal adiposity is an independent risk factor for respiratory distress in COVID-19, adjusted for metabolic syndrome, age, gender and BMI (OR 1.11, 95% CI 1.02 to 1.20, p=0.014). CONCLUSION: This study shows that abdominal adiposity, and not the presence of metabolic syndrome, is associated with clinical deterioration in COVID-19. This prospective study provides further insight into the risk stratification of patients with COVID-19 based on a simple measurement as the waist and hip circumference. TRIAL REGISTRATION NUMBER: NL8580.

Subclinical cardiac dysfunction in obesity patients is linked to autonomic dysfunction: findings from the CARDIOBESE study.

AIMS: Obesity doubles the lifetime risk of developing heart failure. Current knowledge on the role of obesity in causing cardiac dysfunction is insufficient for optimal risk stratification. The aim of this study was first to estimate the prevalence of subclinical cardiac dysfunction in obesity patients and second to investigate the underlying pathophysiology. METHODS AND RESULTS: The CARDIOBESE study is a cross-sectional multicentre study of 100 obesity patients [body mass index (BMI) ≥ 35 kg/m2 ] without known cardiovascular disease and 50 age-matched and gender-matched non-obese controls (BMI ≤ 30 kg/m2 ). Echocardiography was performed, blood samples were collected, and a Holter monitor was affixed. Fifty-nine obesity patients [48 (42-50) years, 70% female] showed subclinical cardiac dysfunction: 57 patients had decreased global longitudinal strain (GLS), and two patients with normal GLS had either diastolic dysfunction or increased brain natriuretic peptide (BNP). Only one non-obese control had diastolic dysfunction, and none had another sign of cardiac dysfunction. Multivariable logistic analysis identified male gender and standard deviation of all NN intervals (SDNN) index, which is a measure of autonomic dysfunction, as independent significant risk factors for subclinical cardiac dysfunction in obesity patients. CONCLUSIONS: There was a high prevalence (61%) of subclinical cardiac dysfunction in obesity patients without known cardiovascular disease, which appeared to be best identified by GLS. Subclinical cardiac dysfunction in obesity was linked to autonomic dysfunction and male gender, and not to the presence of traditional cardiac risk factors, increased C-reactive protein, increased BNP, increased high-sensitivity troponin I, or increased left ventricular mass.