Endothelium-associated biomarkers mid-regional proadrenomedullin and C-terminal proendothelin-1 have good ability to predict 28-day mortality in critically ill patients with SARS-CoV-2 pneumonia: A prospective cohort study

PURPOSE: We assessed the ability of mid-regional proadrenomedullin (MR-proADM) and C-terminal proendothelin-1 (CT-proET-1) to predict 28-day mortality in critically ill patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia. METHODS: Biomarkers were collected during the first seven days in this prospective observational cohort study. We investigated the relationship between biomarkers and mortality in a multivariable Cox regression model adjusted for age and SOFA score. RESULTS: In 105 critically ill patients with confirmed SARS-CoV-2 pneumonia 28-day mortality was 28.6%. MR-proADM and CT-proET-1 were significantly higher in 28-day non-survivors at baseline and over time. ROC curves revealed high accuracy to identify non-survivors for baseline MR-proADM and CT-proET-1, AUC 0.84, (95% CI 0.76–0.92), p < 0.001 and 0.79, (95% CI 0.69–0.89), p < 0.001, respectively. The AUC for prediction of 28-day mortality for MR-proADM and CT-proET-1 remained high over time. MR-proADM ≥1.57 nmol/L and CT-proET-1 ≥ 111 pmol/L at baseline were significant predictors for 28-day mortality (HR 6.80, 95% CI 3.12–14.84, p < 0.001 and HR 3.72, 95% CI 1.71–8.08, p 0.01). CONCLUSION: Baseline and serial MR-proADM and CT-proET-1 had good ability to predict 28-day mortality in critically ill patients with SARS-CoV-2 pneumonia. TRIAL REGISTRATION: NEDERLANDS TRIAL REGISTER, NL8460

Low-Iodine Diet of 4 Days Is Sufficient Preparation for I-131 Therapy in Differentiated Thyroid Cancer Patients

Context: No consensus exists about the optimal duration of the low-iodine diet (LID) in the preparation of I-131 therapy in differentiated thyroid cancer (DTC) patients.Objective: This work aimed to investigate if a LID of 4 days is enough to achieve adequate iodine depletion in preparation for I-131 therapy. In addition, the nutritional status of the LID was evaluated.Methods: In this prospective study, 65 DTC patients treated at 2 university medical centers were included between 2018 and 2021. The patients collected 24-hour urine on days 4 and 7 of the LID and kept a food diary before and during the LID. The primary outcome was the difference between the 24-hour urinary iodine excretion (UIE) on both days.Results: The median 24-hour UIE on days 4 and 7 of the LID were not significantly different (36.1 mcg [interquartile range, 25.4-51.2 mcg] and 36.5 mcg [interquartile range, 23.9-47.7 mcg], respectively, P= .43). On day 4 of the LID, 72.1% of the DTC patients were adequately prepared (24-hour UIE < 50 mcg), and 82.0% of the DTC patients on day 7 (P= .18). Compared to the self-reported regular diet, DTC patients showed a significantly (P< .01) lower percentage of nutrient intake (calories, protein, calcium, iodine, and water) during the LID.Conclusion: The 24-hour UIE on day 4 of the LID did not differ from day 7, and therefore shortening the LID from 7 to 4 days seems justified to prepare DTC patients for I-131 therapy in areas with sufficient iodine intake and may be beneficial to maintain a sufficient nutritional intake during DTC treatment

The Effect of Bolus Vitamin D-3 Supplementation on Distal Radius Fracture Healing: A Randomized Controlled Trial Using HR-pQCT

Vitamin D is an important factor in bone metabolism. Animal studies have shown a positive effect of vitamin D3 supplementation on fracture healing, but evidence from clinical trials is inconclusive. A randomized controlled trial was performed to assess the effect of vitamin D3 supplementation on fracture healing using high-resolution peripheral quantitative computed tomography (HR-pQCT) based outcome parameters. Thirty-two postmenopausal women with a conservatively treated distal radius fracture were included within two weeks post-fracture and randomized to a low-dose (N = 10) and a high-dose (N = 11) vitamin D intervention group receiving a 6-week bolus dose, equivalent to 700 and 1,800 IU vitamin D3 supplementation per day respectively, in addition to a control group (N = 11) receiving no supplementation. After the baseline visit 1-2 weeks post-fracture, follow-up visits were scheduled at 3-4, 6-8 and 12 weeks post-fracture. At each visit, HR-pQCT scans of the fractured radius were performed. Cortical and trabecular bone density and microarchitectural parameters and μFEA derived torsion, compression and bending stiffness were assessed. Additionally, serum markers of bone resorption (C-terminal telopeptide of type I collagen; CTX) and bone formation (N-terminal propeptide of type I procollagen; PINP) were measured. Baseline serum levels of 25(OH)D3 were < 50 nmol/L in 33% of all participants and < 75 nmol/L in 70%. Compared to the control group, high-dose vitamin D3 supplementation resulted in a decreased trabecular number (regression coefficient B: -0.22; p < 0.01) and lower compression stiffness (B: -3.63; p < 0.05, together with an increase in the bone resorption marker CTX (B: 0.062; p < 0.05). No statistically significant differences were observed between the control and low-dose intervention group. In conclusion, the bolus equivalent of 700 U/day vitamin D3 supplementation in a Western postmenopausal population does not improve distal radius fracture healing and an equivalent dose of 1,800 IU/day may be detrimental in restoring bone stiffness during the first 12 weeks of fracture healing

Patients with aldolase B deficiency are characterized by an increased intrahepatic triglyceride content

Context: There is an ongoing debate about whether and how fructose is involved in the pathogenesis of nonalcoholic fatty liver disease (NAFLD). A recent experimental study showed an increased intrahepatic triglyceride (IHTG) content in mice deficient for aldolase B (aldo B−/−), the enzyme that converts fructose-1-phosphate to triose phosphates. Objective: To translate these experimental findings to the human situation. Design: Case-control study. Setting: Outpatient clinic for inborn errors of metabolism. Patients or Other Participants: Patients with hereditary fructose intolerance, a rare inborn error of metabolism caused by a defect in aldolase B (n = 15), and healthy persons matched for age, sex, and body mass index (BMI) (n =15). Main Outcome Measure: IHTG content, assessed by proton magnetic resonance spectroscopy. Results: IHTG content was higher in aldo B−/− patients than controls (2.5% vs 0.6%; P = 0.001) on a background of lean body mass (median BMI, 20.4 and 21.8 kg/m2, respectively). Glucose excursions during an oral glucose load were higher in aldo B−/− patients (P = 0.043). Hypoglycosylated transferrin, a surrogate marker for hepatic fructose-1-phosphate concentrations, was more abundant in aldo B−/− patients than in controls (P < 0.001). Finally, plasma β-hydroxybutyrate, a biomarker of hepatic β-oxidation, was lower in aldo B−/− patients than controls (P = 0.009). Conclusions: This study extends previous experimental findings by demonstrating that aldolase B deficiency also results in IHTG accumulation in humans. It suggests that the accumulation of fructose-1-phosphate and impairment of β-oxidation are involved in the pathogenesis

Relationship between de novo lipogenesis and serum sex hormone binding globulin in humans

OBJECTIVE: Obesity and liver fat are associated with decreased levels of serum sex hormone binding globulin (SHBG). Laboratory studies suggest that hepatic de novo lipogenesis (DNL) is involved in the downregulation of SHBG synthesis. The aim of the present study was to address the role of DNL on serum SHBG in humans. DESIGN: A cross-sectional study examining the association between DNL, measured by stable isotopes, and serum SHBG, stratified by sex. PARTICIPANTS: Healthy men (n = 34) and women (n = 21) were combined from two cross-sectional studies. Forty-two per cent of participants had hepatic steatosis, and the majority were overweight (62%) or obese (27%). RESULTS: DNL was inversely associated with SHBG in women (β: -0.015, 95% CI: -0.030; 0.000), but not in men (β: 0.007, 95% CI: -0.005; 0.019) (p for interaction = .068). Adjustment for study population, age and body mass index did not materially change these results, although statistical significance was lost after adjustment for serum insulin. CONCLUSIONS: An inverse association between DNL and SHBG may explain the decreased SHBG levels that are observed in obesity, at least in women