Nonthyroidal illness syndrome (NTIS) in severe COVID-19 patients: role of T3 on the Na/K pump gene expression and on hydroelectrolytic equilibrium

Background Nonthyroidal Illness Syndrome (NTIS) can be detected in many critical illnesses. Recently, we demonstrated that this condition is frequently observed in COVID-19 patients too and it is correlated with the severity the disease. However, the exact mechanism through which thyroid hormones influence the course of COVID-19, as well as that of many other critical illnesses, is not clear yet and treatment with T4, T3 or a combination of both is still controversial. Aim of this study was to analyze body composition in COVID-19 patients in search of possible correlation with the thyroid function. Methods and findings We report here our experience performed in 74 critically ill COVID-19 patients hospitalized in the intensive care unit (ICU) of our University Hospital in Rome. In these patients, we evaluated the thyroid hormone function and body composition by Bioelectrical Impedance Analysis (BIA) during the acute phase of the disease at admission in the ICU. To examine the effects of thyroid function on BIA parameters we analyzed also 96 outpatients, affected by thyroid diseases in different functional conditions. We demonstrated that COVID-19 patients with low FT3 serum values exhibited increased values of the Total Body Water/Free Fat Mass (TBW/FFM) ratio. Patients with the lowest FT3 serum values had also the highest level of TBW/FFM ratio. This ratio is an indicator of the fraction of FFM as water and represents one of the best-known body-composition constants in mammals. We found an inverse correlation between FT3 serum values and this constant. Reduced FT3 serum values in COVID-19 patients were correlated with the increase in the total body water (TBW), the extracellular water (ECW) and the sodium/potassium exchangeable ratio (Nae:Ke), and with the reduction of the intracellular water (ICW). No specific correlation was observed in thyroid patients at different functional conditions between any BIA parameters and FT3 serum values, except for the patient with myxedema, that showed a picture similar to that seen in COVID-19 patients with NTIS. Since the Na+/K+ pump is a well-known T3 target, we measured the mRNA expression levels of the two genes coding for the two major isoforms of this pump. We demonstrated that COVID-19 patients with NTIS had lower levels of mRNA of both genes in the peripheral blood mononuclear cells (PBMC)s obtained from our patients during the acute phase of the disease. In addition, we retrieved data from transcriptome analysis, performed on human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM)s treated with T3 and we demonstrated that in these cells T3 is able to stimulate the expression of these two genes in a dose-dependent manner. Conclusions In conclusion, we demonstrated that measurement of BIA parameters is a useful method to analyze water and salt retention in COVID-19 patients hospitalized in ICU and, in particular, in those that develop NTIS. Our results indicate that NTIS has peculiar similarities with myxedema seen in severe hypothyroid patients, albeit it occurs more rapidly. The Na+/K+ pump is a possible target of T3 action, involved in the pathogenesis of the anasarcatic condition observed in our COVID-19 patients with NTIS. Finally, measurement of BIA parameters may represent good endpoints to evaluate the benefit of future clinical interventional trials, based on the administration of T3 in patients with NTIS.

What Total Body Water Measurement Should Be Used for Prescribing the Dialysis Dose in Low-Flow Home Daily Dialysis?

<b><i>Introduction:</i></b> In low-flow home daily dialysis (HDD), the dialysis dose is evaluated from the total body water (TBW). TBW can be estimated by anthropometric methods or bioimpedance spectroscopy. <b><i>Methods:</i></b> A multicentric cross-sectional study of patients in HDD for &#x3e;3 months was conducted to assess the correlation and the difference between the anthropometric estimate of TBW (Watson-TBW) and the bioimpedance estimate (BIS-TBW) and to analyse the impact on the dialysate volume prescribed. <b><i>Results:</i></b> Forty patients from 10 centres were included. The median BIS-TBW and Watson-TBW were 35.1 (29.1–41.4 L) and 36.9 (32–42.4 L), respectively. The 2 methods had a good correlation (<i>r</i> = 0.87, <i>p</i> &#x3c; 0.05). However, Bland-Altman analysis showed an overestimation of TBW with Watson’s formula, with a bias of 2.77 L. For 4, 5, or 6 sessions per week, the use of Watson-TBW increases the dialysate prescription per week by 100 L, 45 L, or 10 L, respectively, over our entire cohort. There is no increase in the volume of dialysate prescribed with the 7 sessions per week schedule. <b><i>Conclusion:</i></b> BIS-TBW and Watson-TBW estimation have a good correlation; however, Watson’s equation overestimates TBW. This overestimation is negligible for a prescription frequency of &#x3e;5 sessions per week.

Measurements of Alterations in Bone Mineral Density, and Body Composition in a Group of Type-2 Diabetic Women

Aim: To assess the body composition of fat mass, lean mass, visceral fat mass, and total body water in DM patients and compares their findings with a healthy control group. Material and Methods: A total of 86 people including 40 diabetes Mellitus type 2 matched for sex and age with 46 healthy control participated in the study. BMDs of the lumbar vertebrae and the hip regions like (total femur, femoral neck) were assessed using the DXA technique. The mean age of (DM) group was 59 ± 11.82 years, the height 1.55 ± 0.05 m., the weight 80.82 ± 13.25 kg, and BMI 33.81 ± 6.76 kg/m2. Results: The differences in measurements of the lumbar spine BMD (1.12 ± 0.13 g/cm2), total femur BMD (1.10± 0.17 g/cm2) neck of femur BMD (0.85± 0.35 g/cm2), and total BMD of the body (0.90± 0.06 g/cm2) were highly significant in healthy control group as compared to DM patients 0.84 ± 0.13 g/cm2, 0.99±0.15 g/cm2, 0.82± 0.24 g/cm2 and 0.79 ± 0.09 g/cm2 respectively. Conclusion: The results shows a highly significant in the lumbar spine, total femur, and total BMC, and not significant in the neck of the femur. The total body lean compartment was not significantly different between DM patients and healthy control women groups. The total body water compartment in the DM women group was highly significant lower different comparing with a healthy control group. The mathematical equations to predict total bone density in DM type 2 and healthy control women were calculated.

The influence of fasting and carbohydrate-enriched drink administration on body water amount and distribution: a volunteer randomized study

Background Fasting prior to anesthesia is considered aspiration prophylaxis. However, prolonged food and drink restrictions may increase the risk of other complications. The aim of this study was to assess whether a carbohydrate-enriched drink (Nutricia™ preOp®), recommended by the enhanced recovery after surgery (ERAS) protocol, can improve body hydration in fasting healthy individuals. Methods Measurements were done with the bioelectric impedance analysis with a Fresenius body composition monitor. Body composition, total body water, water distribution, and hemodynamic parameters were measured at the beginning of the study and after 10 h and 12 h of fasting. Patients fasted for 10 h and then were divided into two groups: the control (n = 40) and the pre-op group (n = 41). The pre-op group received 400 mL of Nutricia™ preOp®, as suggested in the ERAS guidance. The two-tailed Student’s t test was used to compare two groups with normally distributed data and homogenous variances; if variances were heterogeneous, Welch’s test was used. The Mann-Whitney U test was used to compare two groups with non-normal data distribution. p < 0.05 was considered statistically significant. Results We found no significant differences between the control and pre-op groups regarding body water distribution and body composition. We did not observe significant losses in the total body water after fasting. Also, blood pressure was not affected by fasting. Conclusion We have proven that pre-op did not impact either body composition or body water. Trial registration ClinicalTrials.gov, NCT04665349. Registered on 11 December 2020—retrospectively registered.