Fish and Shellfish Intake and Diabetes in a Costal Population of the Adriatic

Objective: To examine the association between fish and shellfish intake and diabetes in an island population. Design: Cross-sectional. Setting: Two independent population-based field surveys conducted in Hvar Island of the eastern Adriatic coast of Croatia in May 2007 and May 2008. Subjects: A total of 1,379 adults participated. Results: In multivariable logistic regression models, total fish intake was positively associated with diabetes prevalence in the total population (OR Q4 vs Q1 = 1.64; 95% CI = 1.01-2.66; p-trend = 0.09). Oily fish intake also exhibited a positive association with diabetes prevalence in the total population (OR Q4 vs Q1 = 2.22; 95% CI = 1.35-3.64; p-trend = 0.01) and in analyses stratified by body mass index, males and those with a high waist circumference. Conclusions: The study suggests an association between oily fish intake and diabetes in the population of the Hvar Island in Croatia. Longitudinal studies incorporating measures of persistent organic pollutants and local cooking practices are warranted to identify factors in fatty fish that may influence the development or persistence of diabetes

Bleeding and thrombotic risk in pregnant women with Fontan physiology

Background/objectives Pregnancy may potentiate the inherent hypercoagulability of the Fontan circulation, thereby amplifying adverse events. This study sought to evaluate thrombosis and bleeding risk in pregnant women with a Fontan.  Methods We performed a retrospective observational cohort study across 13 international centres and recorded data on thrombotic and bleeding events, antithrombotic therapies and pre-pregnancy thrombotic risk factors.  Results We analysed 84 women with Fontan physiology undergoing 108 pregnancies, average gestation 33 +/- 5 weeks. The most common antithrombotic therapy in pregnancy was aspirin (ASA, 47 pregnancies (43.5%)). Heparin (unfractionated (UFH) or low molecular weight (LMWH)) was prescribed in 32 pregnancies (30%) and vitamin K antagonist (VKA) in 10 pregnancies (9%). Three pregnancies were complicated by thrombotic events (2.8%). Thirty-eight pregnancies (35%) were complicated by bleeding, of which 5 (13%) were severe. Most bleeds were obstetric, occurring antepartum (45%) and postpartum (42%). The use of therapeutic heparin (OR 15.6, 95% CI 1.88 to 129, p=0.006), VKA (OR 11.7, 95% CI 1.06 to 130, p=0.032) or any combination of anticoagulation medication (OR 13.0, 95% CI 1.13 to 150, p=0.032) were significantly associated with bleeding events, while ASA (OR 5.41, 95% CI 0.73 to 40.4, p=0.067) and prophylactic heparin were not (OR 4.68, 95% CI 0.488 to 44.9, p=0.096). Conclusions Current antithrombotic strategies appear effective at attenuating thrombotic risk in pregnant women with a Fontan. However, this comes with high (>30%) bleeding risk, of which 13% are life threatening. Achieving haemostatic balance is challenging in pregnant women with a Fontan, necessitating individualised risk-adjusted counselling and therapeutic approaches that are monitored during the course of pregnancy

Optimal Sweep Gas to Blood Flow Ratio (V/Q) for Initiation of Cardiopulmonary Bypass in a Pediatric Patient Population: A Retrospective Analysis

The optimal setting to achieve a suitable PaCO2 value of 35–45 mmHg upon initiating cardiopulmonary bypass (CPB) in the pediatric population is undefined in the literature. Sweep gas is set upon initiating and modified throughout CPB to reduce potential complications related to compensatory metabolic acidosis or metabolic alkalosis and associated cerebral blood flow fluctuations. This study retrospectively examined 1,077 CPB cases for which PaCO2 values were no less than 30 mmHg and no greater than 50 mmHg on the pre-CPB blood gas result. Through an observation of the results, we attempted to determine the optimal sweep gas setting upon initiating CPB to obtain a physiologic PaCO2 value of 35–45 mmHg. The probability of achieving an optimal PaCO2 value was modeled as a function of the average sweep gas to blood flow ratio during the period before the first blood gas on CPB. The median sweep gas to blood flow ratio (V/Q) was .64 (.51; .76), with a median first PaCO2 value on CPB of 42 mmHg (38.8; 45). A .6 V/Q had an odds ratio (OR) of 1.57 of obtaining a PaCO2 value between 35 and 45 mmHg on the first CPB blood gas when compared with a .4 V/Q (Figure

Attainment of ‘5-2-1-0’ obesity recommendations in preschool-aged children

Obesity prevention guidelines recommend children eat ≥5 servings of fruits and vegetables, view ≤2h of screen time, participate in 1h of physical activity, and consume 0 sugar-sweetened beverages daily, commonly known as ‘5-2-1-0’. We sought to determine: the extent to which preschool-aged children attending child care meet these guidelines, predictors of attainment, and associations of attainment with weight status. We analyzed in 2016, 24-hour dietary, physical activity, and screen time data collected in 2009–10 from 398 preschool-aged children in 30 child-care centers in Cincinnati, OH. Dietary intake, screen time and body-mass index (BMI) were obtained by research staff during child care and from parents when at home. Accelerometers measured physical activity. Mixed-effects models and generalized estimating equations were used to determine associations between ‘5-2-1-0’ recommendations, demographic variables, and BMI z-scores. Average child age was 4.3±0.7years; 26% had a BMI≥85th percentile. Seventeen percent of children with complete dietary data (n=307) consumed ≥5 servings of fruits and vegetables and 50% consumed 0 sugar-sweetened beverages. <1% with complete physical activity data (n=386) met the activity recommendation; 81% of children (n=379) had ≤2h of screen time. Only 1 child met all of the ‘5-2-1-0’ recommendations. There were no consistent demographic predictors of attaining individual recommendations. An additional hour of screen time was associated with a 0.11 (SD 0.06) increase in BMI z-score. Our data suggests there is ample room to increase fruit and vegetable intake and physical activity in preschool-aged children. Keywords: Obesity prevention, Nutrition recommendations, Physical activity guidelines, Screen time, Child car

Microbiota-derived butyrate dampens linaclotide stimulation of the guanylate cyclase C pathway in patient-derived colonoids.

BACKGROUND & AIMS: Disorders of gut-brain interaction (DGBI) are complex conditions that result in decreased quality of life and a significant cost burden. Linaclotide, a guanylin cyclase C (GCC) receptor agonist, is approved as a DGBI treatment. However, its efficacy has been limited and variable across DGBI patients. Microbiota and metabolomic alterations are noted in DGBI patients, provoking the hypothesis that the microbiota may impact the GCC response to current therapeutics. METHODS: Human-derived intestinal organoids were grown from pediatric DGBI, non-IBD colon biopsies (colonoids). Colonoids were treated with 250 nM linaclotide and assayed for cGMP to develop a model of GCC activity. Butyrate was administered to human colonoids overnight at a concentration of 1 mM. Colonoid lysates were analyzed for cGMP levels by ELISA. For the swelling assay, colonoids were photographed pre- and post-treatment and volume was measured using ImageJ. Principal coordinate analyses (PCoA) were performed on the Bray-Curtis dissimilarity and Jaccard distance to assess differences in the community composition of short-chain fatty acid (SCFA) producing microbial species in the intestinal microbiota from pediatric patients with IBS and healthy control samples. KEY RESULTS: Linaclotide treatment induced a significant increase in [cGMP] and swelling of patient-derived colonoids, demonstrating a human in vitro model of linaclotide-induced GCC activation. Shotgun sequencing analysis of pediatric IBS patients and healthy controls showed differences in the composition of commensal SCFA-producing bacteria. Butyrate exposure significantly dampened linaclotide-induced cGMP levels and swelling in patient-derived colonoids. CONCLUSIONS & INFERENCES: Patient-derived colonoids demonstrate that microbiota-derived butyrate can dampen human colonic responses to linaclotide. This study supports incorporation of microbiota and metabolomic assessment to improve precision medicine for DGBI patients.http://deepblue.lib.umich.edu/bitstream/2027.42/191988/2/Neurogastroenterology Motil - 2023 - Velez Lopez - Microbiota‐derived butyrate dampens linaclotide stimulation of the.pdfPublished versionDescription of Neurogastroenterology Motil - 2023 - Velez Lopez - Microbiota‐derived butyrate dampens linaclotide stimulation of the.pdf : Published versio

Factors leading to supranormal cardiac index in pediatric pulmonary hypertension patients treated with parenteral prostanoid therapy

Abstract Parenteral prostanoid therapy (PPT) can result in supranormal cardiac index (SCI; >4 L/min/m2) in pediatric pulmonary hypertension (PPH) patients. We evaluated the incidence, hemodynamic factors, and outcomes associated with SCI in PPH. This retrospective cohort study included 22 PPH patients on PPT from 2005 to 2020. Hemodynamic profiles were compared between the baseline and 3–6 month follow‐up catheterization in the SCI and non‐SCI cohorts. Cox regression analysis examined time to composite adverse outcome (CAO; Potts shunt, lung transplant, or death) controlling for initial disease severity. SCI developed in 17 (77%) patients, of whom 11 (65%) developed SCI within 6 months. The SCI cohort was characterized by significant augmentation of cardiac index (CI) and stroke volume (SV) as well as reductions in systemic vascular resistance (SVR) and pulmonary vascular resistance (PVR). Conversely, the non‐SCI cohort had unchanged SV despite a modest rise in CI as well as persistent vasoconstriction. After median follow‐up of 4.3 years (range 0.2–13 years), non‐SCI patients were at significantly increased risk for the CAO (5/5: three deaths, two Potts shunts) compared with SCI patients (5/17: two deaths, three lung transplants; adjusted hazard ratio 14.0 [95% confidence interval: 2.1–91.3], p < 0.001). A majority of PPH patients developed SCI within 6–12 months of starting PPT and demonstrated lower risk of adverse outcomes compared with non‐SCI patients. These data suggest that change in SVR and SV after 3–6 months of PPT may be early markers of therapeutic response and prognosis

mDixon ECG-gated 3-dimensional cardiovascular magnetic resonance angiography in patients with congenital cardiovascular disease

Abstract Background Cardiovascular magnetic resonance (CMR) angiography (CMRA) is an important non-invasive imaging tool for congenital heart disease (CHD) and aortopathy patients. The conventional 3D balanced steady-state free precession (bSSFP) sequence is often confounded by imaging artifacts. We sought to compare the respiratory navigated and electrocardiogram (ECG) gated modified Dixon (mDixon) CMRA sequence to conventional non-gated dynamic multi-phase contrast enhanced CMRA (CE-CMRA) and bSSFP across a variety of diagnoses. Methods We included 24 patients with CHD or aortopathy with CMR performed between September 2017 to December 2017. Each patient had undergone CE-CMRA, followed by a bSSFP and mDixon angiogram. Patients with CMR-incompatible implants or contraindications to contrast were excluded. The studies were rated according to image quality at a scale from 1 (poor) to 4 (excellent) based on diagnostic adequacy, artifact burden, vascular border delineation, myocardium-blood pool contrast, and visualization of pulmonary and systemic veins and coronaries. Contrast-to-noise ratio (CNR), signal-to-noise ratio (SNR) and quantitative vascular measurements were compared between the two gated sequences. Bland-Altman plots were generated to compare paired measures. Results All scans were diagnostically adequate. Mean (SD) quality scores were 3.4 (0.7) for the mDixon, 3.2 (0.5) for the bSSFP and 3.4 (0.5) for the CE-CMRA. Qualitatively, the intracardiac anatomy and myocardium-blood pool definition were better in the bSSFP; however, mDixon images showed enhanced vessel wall sharpness with less blurring surrounding the anatomical borders distally. Coronary origins were identified in all cases. Pulmonary veins were visualized in 92% of mDixon sequences, 75% of bSSFP and 96% of CE-CMRA. Similarly, neck veins were identified in 92, 83 and 96% respectively. Artifacts prevented vascular measurement in 6/192 (3%) and 4/192 (2%) of total vascular measurements for the mDixon and bSSFP, respectively. However, the size of signal void and field distortion were significantly worse in the latter, particularly for flow and metal induced artifacts. Conclusion In patients with congenital heart disease, ECG gated mDixon angiography yields high fidelity vascular images including better delineation of head and neck vasculature and pulmonary veins and fewer artifacts than the comparable bSSFP sequence. It should be considered as the preferred strategy for successful CHD imaging in patients with valve stenosis, vascular stents, or metallic implants