<b><i>Cumulative impact of metabolic syndrome components on micro- and macrovascular disease risk in patients with metabolic dysfunction-associated steatotic liver disease: a real-world data analysis</i></b>

Introduction The cumulative impact of metabolic syndrome (MetS) components on micro- and macrovascular disease in metabolic dysfunction-associated steatotic liver disease (MASLD) is unclear. We aimed to determine whether the number of the MetS components increases risk of micro- and macrovascular disease in patients with MASLD.Methods We performed a retrospective cohort study of electronic medical records using the TriNetX network, a global federated database. The exposure arm was patients with hepatic steatosis (defined via ICD-10 coding, or modified hepatic steatosis index), and ≥1 MetS components (obesity/central adiposity, insulin resistance, hypertension, or dyslipidaemia), compared with a reference arm of adults without any MetS components or hepatic steatosis. We propensity score matched (1:1) for confounders with 5 years of follow-up. Primary outcomes included microvascular (peripheral neuropathy, retinopathy, nephropathy) and macrovascular (cardiovascular events, cerebrovascular accidents, peripheral vascular disease) disease. Secondary analyses assessed the impact of additional MetS components on these outcomes, as well as the impact of sex. Results MASLD, defined by hepatic steatosis and insulin resistance (n=15,937), carried the highest risk of microvascular disease (HR 13.93 (95% CI 8.55-22.68)), whilst MASLD, defined by hepatic steatosis and hypertension (n=53,028), carried the highest risk of macrovascular disease (7.23 (6.45-8.13)). MASLD with all MetS components carried greatest risk of both micro- (31.20 (28.88-33.70) (n=462,789)) and macrovascular (8.04 (7.33-8.82) (n=336,010)) disease.Conclusion We demonstrate a differential effect of MetS components on micro- and macrovascular disease risk in patients with MASLD, with a cumulative impact of multiple MetS on overall risk. The impact of MetS components was most pronounced in women. Aggressive metabolic risk factor management is critical for prevention of micro- and macrovascular complications. <br/

2008 Inter-laboratory Comparison Study of a Reference Material for Nutrients in Seawater

Autoclaved natural seawater collected in the North Pacific Ocean was used as a reference material for nutrients in seawater (RMNS) during an inter-laboratory comparison (I/C) study conducted in 2008. This study was a follow-up to previous studies conducted in 2003 and 2006. A set of six samples was distributed to each of 58 laboratories in 15 countries around the globe, and results were returned by 54 of those laboratories (15 countries). The homogeneities of samples used in the 2008 I/C study, based on analyses for three determinants, were improved compared to those of samples used in the 2003 and 2006 I/C studies. Results of these I/C studies indicate that most of the participating laboratories have an analytical technique for nutrients that is sufficient to provide data of high comparability. The differences between reported concentrations from the same laboratories in the 2006 and 2008 I/C studies for the same batch of RMNS indicate that most of the laboratories have been maintaining internal comparability for two years. Thus, with the current high level of performance in the participating laboratories, the use of a common reference material and the adaptation of an internationally accepted nutrient scale system would increase comparability among laboratories worldwide, and the use of a certified reference material would establish traceability. In the 2008 I/C study we observed a problem of non-linearity of the instruments of the participating laboratories similar to that observed among the laboratories in the 2006 I/C study. This problem of non-linearity should be investigated and discussed to improve comparability for the full range of nutrient concentrations. For silicate comparability in particular, we see relatively larger consensus standard deviations than those for nitrate and phosphate

Denosumab, for osteoporosis, reduces the incidence of type 2 diabetes, risk of foot ulceration and all-cause mortality in adults, compared with bisphosphonates: An analysis of real-world, cohort data, with a systematic review and meta-analysis.

AimTo evaluate the impact of denosumab on (i) the incidence of type 2 diabetes (T2D), and (ii) long-term health outcomes (microvascular [neuropathy, retinopathy, nephropathy] and macrovascular [cardiovascular disease, cerebrovascular accident] complications, and all-cause mortality) in patients with T2D, before (iii) combining results with prior studies using meta-analysis.MethodsA retrospective analysis of data in a large global federated database (TriNetX; Cambridge, MA) was conducted from 331 375 patients, without baseline T2D or cancer, prescribed either denosumab (treatment, n = 45 854) or bisphosphonates (control, n = 285 521), across 83 healthcare organizations. Propensity score matching (1:1) of confounders was undertaken that resulted in 45 851 in each cohort. Secondary analysis further evaluated the impact of denosumab on long-term health outcomes in patients with T2D. Additionally, we systematically searched prior literature that assessed the association between denosumab and T2D. Estimates were pooled using random-effects meta-analysis. Risk of bias and evidence quality were assessed using Cochrane-endorsed tools.ResultsDenosumab (vs. bisphosphonates) was associated with a lower risk of incident T2D over 5 years (hazard ratio 0.83 [95% confidence interval {CI} 0.78-0.88]). Secondary analysis showed significant risk reduction in all-cause mortality (0.79 [0.72-0.87]) and foot ulceration (0.67 [0.53-0.86]). Also, pooled results from four studies (three observational, one randomized controlled trial) following meta-analysis showed a reduced relative risk (RR [95% CI]) for incident T2D in patients prescribed denosumab (0.83 [0.79-0.87]) (I2 = 10.76%).ConclusionsThis is the largest cohort study to show that denosumab treatment is associated with a reduced RR of incident T2D, as well as an associated reduced RR of all-cause mortality and microvascular complications, findings that may influence guideline development in the treatment of osteoporosis, particularly in patients who are at a high risk of T2D

The chemoprotective effect of anti-platelet agents on cancer incidence in people with non-alcoholic fatty liver disease (NAFLD): a retrospective cohort study.

BackgroundNon-alcoholic fatty liver disease (NAFLD) is associated with an increased incidence of hepatic and extrahepatic cancers, in particular those linked to obesity. In people with chronic liver disease, aspirin may confer protection against hepatocellular carcinoma (HCC). We explore the potential chemoprotective effect of aspirin/other anti-platelet agents on obesity-related cancers, including HCC in people with NAFLD.MethodsWe performed a retrospective cohort study of anonymised electronic medical records using the TriNetX network (Cambridge, MA, USA), a global federated database. We identified adults aged 18 or over with a diagnosis of NAFLD, prior to commencing antiplatelet agents. Two groups were created: antiplatelet (1) versus no antiplatelet use (2). We propensity score matched for nine variables. Antiplatelet use was defined as aspirin, ticagrelor, cangrelor, clopidogrel or prasugrel use for at least 1 year. The outcomes of interest were incidence of HCC and other obesity-related cancers. Follow-up was for 5 years. We performed subgroup analyses on aspirin users only and stratified findings for sex and age. Sensitivity analysis was conducted on individuals with 3- and 5-year aspirin exposure.ResultsPost matching, there were 42,192 people per group. Antiplatelet use in people with NAFLD was associated with statistically significant reduction in all obesity-related cancers (HR 0.71, 95% CI 0.65-0.78, p ConclusionsAspirin/antiplatelet agents may have a role in primary cancer prevention in people living with NAFLD

Risk of type 2 diabetes, MASLD and cardiovascular disease in people living with polycystic ovary syndrome.

Abstract Background Polycystic ovary syndrome (PCOS) is associated with adverse clinical outcomes which may differ according to PCOS phenotype. Methods Using UK Biobank data, we compared the incidence of type 2 diabetes (T2D), metabolic dysfunction associated steatotic liver disease (MASLD), cardiovascular disease (CVD), hormone-dependent cancers, and dementia between PCOS participants, and age- and BMI-matched controls. We also compared multi-organ (liver, cardiac and brain) magnetic resonance imaging (MRI) data and examined the impact of PCOS phenotype (hyperandrogenic and normoandrogenic) on these outcomes. Results We included 1008 women with PCOS (defined by diagnostic codes, self-reported diagnoses, or clinical/biochemical features of hyperandrogenism and a/oligomenorrhoea), and 5017 matched controls (5:1 ratio); median age, 61 years, body mass index, 28.4 kg/m². Adjusted Cox proportional hazard modelling demonstrated PCOS participants had greater incident T2D (HR 1.47; 95% CI, 1.11-1.95) and all-cause CVD (1.76; 1.35-2.30). No between-group differences existed for cancers or dementia. Liver MRI confirmed more PCOS participants had hepatic steatosis (proton density fat fraction &amp;gt;5.5%: 35.9 vs. 23.9% (p=0.02)), and higher fibroinflammation (corrected T1 (cT1) (721.4 vs. 701.5ms (p=&amp;lt;0.01)), vs. controls. No between-group difference existed for cardiac (bi-ventricular/atrial structure and function) or brain (grey and white matter volumes) imaging. Normoandrogenic (but not hyperandrogenic) PCOS participants had greater incident all-cause CVD (1.82; 1.29-2.56) while hyperandrogenic (but not normoandrogenic) PCOS participants were more likely to have hepatic steatosis (8.96 vs. 6.04 vs. 5.23% (p=0.03)) with greater fibro-inflammation (776.3 vs. 707.7 vs. 701.9 ms (p=&amp;lt;0.01)). Conclusions Cardiometabolic disease may be increased in PCOS patients with a disease phenotype-specific pattern. </jats:sec

Variability of alkalinity and the alkalinity-salinity relationship in the tropical and subtropical surface ocean

The variability of total alkalinity (TA) and its relationship with salinity in the tropical and subtropical surface ocean were examined using data collected in various marine environments from a ship of opportunity. In the open ocean regions of the Atlantic, Pacific, and Indian Oceans, sea surface TA variability was observed to be mainly controlled by the simple dilution or concentration (SDC) effect of precipitation and evaporation, and the measured concentrations of TA agreed well with those predicted from salinity and temperature. Non-SDC changes in alkalinity in ocean margins and inland seas were examined by comparing the salinity-normalized alkalinity with that of the open ocean end-member. Non-SDC alkalinity additions to the western North Atlantic margin, eastern North Pacific margin, and Mediterranean Sea were identified, which mainly resulted from river inputs and shelf currents. In contrast, removal of TA through formation and sedimentation of calcium carbonate was observed to be an important control in the Red Sea. The concentration of the river end-member can only be reliably derived from the y intercept of TA-S regression (TAS0) in river-dominated systems such as estuaries and river plumes. In coastal regions where other processes (evaporation, shelf currents, upwelling, calcification, etc.) are more influential, TAS0 can significantly deviate from the river water concentration and hence be an unreliable indicator of it. Negative values of TAS0 can result from non-SDC TA removal at the low salinity end (relative to the salinity of the oceanic end-member) and/or non-SDC TA addition at high salinities (as occurs in the Mediterranean Sea)

Application and assessment of a membrane-based pCO2 sensor under field and laboratory conditions

ABSTRACT: The principle, application, and assessment of the membrane-based ProOceanus CO2-Pro sensor for partial pressure of CO2 (pCO2) are presented. The performance of the sensor is evaluated extensively under field and laboratory conditions by comparing the sensor outputs with direct measurements from calibrated pCO2 measuring systems and the thermodynamic carbonate calculation of pCO2 from discrete samples. Under stable laboratory condition, the sensor agreed with a calibrated water-air equilibrator system at –3.0 ± 4.4 μatm during a 2-month intercomparison experiment. When applied in field deployments, the larger differences between measurements and the calculated pCO2 references (6.4 ± 12.3 μatm on a ship of opportunity and 8.7 ± 14.1 μatm on a mooring) are related not only to sensor error, but also to the uncertainties of the references and the comparison process, as well as changes in the working environments of the sensor. When corrected against references, the overall uncertainties of the sensor results are largely determined by those of the pCO2 references (± 2 and ± 8 μatm for direct measurements and calculated pCO2, respectively). Our study suggests accuracy of the sensor can be affected by temperature fluctuations of the detector optical cell and calibration error. These problems have been addressed in more recent models of the instrument through improving detector temperature control and through using more accurate standard gases. Another interesting result in our laboratory test is the unexpected change in alkalinity which results in significant underestimation in the pCO2 calculation as compared to the direct measurement (up to 90 μatm)

Nutrients measured on water bottle samples during Charles Darwin cruise CD84

Biochemistry measured on water bottle samples during Charles Darwin cruise CD8