Effect of Low-Dose Iron Supplementation on Early Development in Breastfed Infants: A Randomized Clinical Trial.

Importance: Breastfed infants are at risk of iron deficiency, which is associated with suboptimal development. There is a paucity of evidence on the effects of iron supplementation on child development, and current guidelines are divergent. Objective: To assess whether daily iron supplementation, 1 mg/kg, between 4 and 9 months in exclusively or predominantly breastfed infants improves psychomotor development at 12 months. Design, Setting, and Participants: This was a randomized, double-blind, placebo-controlled trial conducted between December 2015 and May 2020 with follow-up through May 2023 in an outpatient setting in Poland and Sweden. Participants were healthy singleton infants born at term with birth weight greater than 2500 g who were exclusively or predominantly breastfed (>50%) and did not have anemia (hemoglobin >10.5 g/dL) at age 4 months. Exclusion criteria included major illness, congenital anomaly, food allergy, and difficulty communicating with caregivers. Interventions: Iron (micronized microencapsulated ferric pyrophosphate), 1 mg/kg, or placebo (maltodextrin) once daily from age 4 to 9 months. Main Outcomes and Measures: The primary outcome was psychomotor development assessed by motor score of Bayley Scales of Infant and Toddler Development III at 12 months, adjusted for gestational age, sex, and maternal education. Secondary outcomes included cognitive and language scores at 12 months; motor, cognitive, and language scores at 24 and 36 months; iron deficiency (serum ferritin <12 ng/mL), and iron deficiency anemia (iron deficiency and hemoglobin <10.5 g/dL) at 12 months. Results: Of 221 randomized infants (111 female), 200 (90%) were included in the intention-to-treat analysis (mean [SD] age, 12.4 [0.8] months). Iron supplementation (n = 104) compared to placebo (n = 96) had no effect on psychomotor development (mean difference [MD] for motor score, -1.07 points; 95% CI, -4.69 to 2.55), cognitive score (MD, -1.14; 95% CI, -4.26 to 1.99), or language score (MD, 0.75; 95% CI, -2.31 to 3.82) at 12 months. There were no significant differences at 24 and 36 months. The intervention did not reduce the risk for iron deficiency (relative risk [RR], 0.46; 95% CI, 0.16 to 1.30) or iron deficiency anemia (RR, 0.78; 95% CI, 0.05 to 12.46) at 12 months. Conclusion and Relevance: No benefit was found with daily low-dose iron supplementation between 4 and 9 months with respect to psychomotor development, risk of iron deficiency, or iron deficiency anemia among breastfed infants in a setting of low risk of anemia. Trial Registration: ClinicalTrials.gov Identifier: NCT02242188.

The Influence of Deterioration of Kidney Function on the Diagnostic Power of Laboratory Parameters Used in the Prognostic Classification of AL Amyloidosis.

There is a possibility that renal dysfunction may potentially reduce the diagnostic power of the laboratory parameters Tn, NT-proBNP and sFLC levels, used in the current prognostic classification of AL amyloidosis and the diagnosis of heart involvement by amyloid. In this study, the impact of lowering the eGFR value on the usefulness of these parameters in the prognosis and diagnosis of the presence of amyloid in the myocardium was assessed in a group of 71 patients with newly diagnosed primary amyloidosis. The assessment of diagnostic power of laboratory parameters was performed on the entire study group, and in the ranges of eGFR ≥ 60 and < 60 mL/min/1.73 m2. It has been proven that, with a decrease in the eGFR value, the concentrations of NT-proBNP and the κ uninvolved light chains increase significantly (p < 0.001). To assess the diagnostic power of laboratory parameters used in the diagnosis of myocardial involvement in patients with AL amyloidosis, an ROC analysis was performed. The highest values of AUC were obtained for the NT-proBNP concentration (AUC = 0.906). The lowest values of the AUC and Youden's index were obtained for the dFLC values (AUC = 0.723), and involved κ FLC concentration (AUC = 0.613). For all compared parameters, the smallest values of the AUC were obtained for eGFR (<60 mL/min/1.73 m2). It seems that the most suitable cardiac parameter used in the prognostic classification of AL amyloidosis, independent of renal function, is TnI. It should be noted that a concentration of involved λ chains hada higher diagnostic power to assess the heart involvement, compared to the routinely used "cardiac parameters", TnI and NT-proBNP. It can therefore be an additional parameter used to assess the presence of amyloid in the myocardium. A decrease in eGFR value influenced the change in the diagnostic cut-off points of the most analyzed laboratory parameters. Finally, it is concluded that lowering the eGFR value reduces the utility of laboratory parameters used in the prognostic classification of AL amyloidosis.

Neutrophil Extracellular Traps (NETs) and Hypercoagulability in Plasma Cell Dyscrasias-Is This Phenomenon Worthy of Exploration?

Plasma cell dyscrasias (PCDs) are neoplastic diseases derived from plasma cells. Patients suffering from PCDs are at high risk of hypercoagulability and thrombosis. These conditions are associated with disease-related factors, patient-related factors, or the use of immunomodulatory drugs. As PCDs belong to neoplastic diseases, some other factors related to the cancer-associated hypercoagulability state in the course of PCDs are also considered. One of the weakest issues studied in PCDs is the procoagulant activity of neutrophil extracellular traps (NETs). NETs are web-like structures released from neutrophils in response to different stimuli. These structures are made of deoxyribonucleic acid (DNA) and bactericidal proteins, such as histones, myeloperoxidase, neutrophil elastase, and over 300 other proteins, which are primarily stored in neutrophil granules. NETs immobilize, inactivate the pathogens, and expose them to specialized cells of immune response. Despite their pivotal role in innate immunity, they contribute to the development and exacerbation of autoimmune diseases, trigger inflammatory response, or even facilitate the formation of cancer metastases. NETs were also found to induce activity of coagulation and are considered one of the most important factors inducing thrombosis. Here, we summarize how PCDs influence the release of NETs, and hypothesize whether NETs contribute to hypercoagulability in PCDs patients.

Cell Population Data and Serum Polyclonal Immunoglobulin Free Light Chains in the Assessment of COVID-19 Severity.

Distinguishing between severe and nonsevere COVID-19 to ensure adequate healthcare quality and efficiency is a challenge for the healthcare system. The aim of this study was to assess the usefulness of CBC parameters together with analysis of FLC serum concentration in risk stratification of COVID-19. MATERIALS AND METHODS: CBC was analyzed in 735 COVID ICU, COVID non-ICU, and non-COVID ICU cases. FLC concentration was analyzed in 133 of them. RESULTS: COVID ICU had neutrophils and lymphocytes with the greatest size, granularity, and nucleic acid content. Significant differences in concentrations of κ and λ FLCs were shown between COVID ICU and COVID non-ICU. However, no difference was found in the κ/λ ratio between these groups, and the ratio stayed within the reference value, which indicates the presence of polyclonal FLCs. FLC κ measurement has significant power to distinguish between severe COVID-19 and nonsevere COVID-19 (AUC = 0.7669), with a sensitivity of 86.67% and specificity of 93.33%. The κ coefficients' odds ratio of 3.0401 was estimated. CONCLUSION: It can be concluded that the results obtained from the measure of free light immunoglobulin concentration in serum are useful in distinguishing between severe and nonsevere COVID-19.

The Role of Light Kappa and Lambda Chains in Heart Function Assessment in Patients with AL Amyloidosis.

There are reports indicating that myocardial dysfunction in systemic immunoglobulin light chain amyloidosis (AL amyloidosis) stems not only from the amyloid deposit in the organ but also the cardiotoxicity of the amyloid precursor free light chains (FLCs) circulating in the blood. The aim of the study is to analyze the role of sFLC κ and λ in the assessment of heart involvement and the degree of myocardial damage in AL amyloidosis. The study involved 71 patients diagnosed with primary AL amyloidosis. The relationship between sFLC concentrations and cardiac biochemical and echocardiographic parameters was assessed. The median concentrations of N-terminal pro b-type natriuretic peptide(NT-proBNP) and troponin I (TnI) were significantly higher in patients with amyloids formed from monoclonal λ chains compared to patients with monoclonal κ proliferation. In patients with heart involvement by amyloids formed from monoclonal FLC, the study demonstrated a statistically significant positive correlation between the concentration of monoclonal antibody λ chain and TnI (R = 0.688; p < 0.05), NT-proBNP (R = 0.449; p < 0.05), and the value of diastolic dimension of the interventricular septum (IVS; R = 0.496, p < 0.05). The above data indicate that the presence of monoclonal λ chains in patients with AL amyloidosis may be associated with more severe damage to cardiomyocytes and dysfunction of the myocardium.

Comparison of 3 Times a Week 4- and 5-Hour In-Center Hemodialysis Sessions with Use of Continuous Non-Invasive Hemodynamic Monitoring.

BACKGROUND Very aggressive ultrafiltration rate (lasting 3.5-4 h) may result in inadequate hemodialysis (HD). Our aim was to characterize HD-induced cardiovascular adaptation and its links to fluid removal during 4- vs. 5-h HD sessions. MATERIAL AND METHODS The study involved 50 HD patients. A Cardioscreen device (Messtechnik, Ilmenau, Germany) was used to perform non-invasive hemodynamic measurements during mid-week HD sessions. Body fluids and nutritional status were assessed with a Body Composition Monitor (Fresenius Medical Care). Clinical and laboratory data were also analyzed. RESULTS It was shown that when comparing 3 times a week 4- vs. 5-h dialysis sessions, body mass index (BMI [kg/m²]), Kt/V, and ultrafiltration volume (UFV [mL]) were significantly lower in the 4-h dialysis group (23.1±3.5 vs. 27.1±4.7; 1.36±0.28 vs. 1.55±0.23; 1770±601 vs. 2831±836; P<0.05, respectively). Cardiac index (CI [L/min/m²]) and thoracic fluid content (TFC [1/kW]) were significantly reduced in 4-h dialysis sessions (3.1±0.6 to 2.7±0.7; 35.1±8.4 to 32.8±6.8; P<0.05, respectively). In patients treated with 5-h dialysis sessions, we found that heart rate (HR [bpm]) was significantly increased (69±10 to 74±15; P<0.05) and TFC was reduced (34.3±8.9 to 31.5±8.2; P<0.05). In patients treated with 4-h dialysis sessions, systemic vascular resistance index (SVRI [dyn·s·cm^-5/m²]) increased from 2369±799 before HD to 2592±735 after HD (P=0.342). CONCLUSIONS The obtained data indicate that in extended (5-h) HD sessions, hemodynamic compensation occurred with increased HR, while in short (4-h) HD sessions, compensation occurred with increased SVRI. Providing longer but less intensive HD is more physiologic than the conventional therapy, and will improve patient tolerability and clinical outcomes.

Assessment of Volumetric Hemodynamic Parameters and Body Composition in Stable Renal Transplant Recipients.

BACKGROUND Cardiovascular disease (CVD) has been associated with decreased graft survival and increased complications in renal transplant recipients (RTRs). The objectives of this study were to explore the relationship between body composition and hemodynamic parameters (cardiac index [CI] and systemic vascular resistance index [SVRI]) in RTRs. MATERIAL AND METHODS The study included 80 RTRs (mean age: 51±8 yrs) who had been admitted to our Nephrology and Transplantology Clinic at 0.5 to 28 years after KTx. The control groups consisted of the 40 patients receiving hemodialysis and 20 health-care professionals. A Cardioscreen 1000 monitor (Messtechnik, Ilmenau, Germany) was used to perform non-invasive hemodynamic measurements. Body composition was studied using a Tanita BC 418 body composition analyzer (Tanita Corp., Tokyo, Japan). Clinical and laboratory data were also analyzed. RESULTS One-way ANOVA confirmed statistically significant differences between RTRs, HD patients, and the control group in CI (2.8±0.3 vs. 3.1±0.7 vs. 3.5±0.6 L/min/m2, P<0.001, respectively) and SVRI (2619±492 vs. 2307±701 vs. 2012±452 d·s/cm-5/m², P<0.001, respectively). In RTRs with functioning AVF, our study revealed significantly higher CI (2.9±0.3 vs. 2.7±0.4 L/min/m², P=0.004) and significantly lower SVRI (2497±286 vs. 2729±605 d·s/cm-5/m², P=0.035). CONCLUSIONS In conclusion, our data indicate that cardiovascular manifestations in the RTRs group are mainly related to decreased CI and HR in addition to increased SVRI with high arterial blood pressure.

Contribution of volume overload to the arterial stiffness of hemodialysis patients.

Arterial stiffness is evaluated with the measurement of pulse wave velocity (PWV), while overhydration (OH) and nutritional status are evaluated with bioimpedance spectroscopy (BIS). In this study, we investigated the effect of a single dialysis session on arterial stiffness, hydration status, and laboratory parameters. The observational, cross-sectional, cohort study included 71 HD patients with mean age 64 ± 16 yrs. A Complior device was used to perform PWV measurements. The patients were examined immediately before and 15 min after a mid-week hemodialysis session. Body fluids and nutritional status were studied using a Body Composition Monitor (BCM), Fresenius Medical Care. Clinical and laboratory data were also analyzed. Multivariate regression analysis of PWV before HD showed that an OH increase of 1 L relate to a PWV parameter rise before HD of 0.523 m/s. Multivariate regression analysis of PWV after HD showed that a rise of central SBP after HD of 10 mmHg relate to a PWV increase after HD of 0.707 m/s. Our data indicate that hydration status and blood pressure may be major determinants of PWV in HD patients.

Assessment of Arterial Stiffness, Volume, and Nutritional Status in Stable Renal Transplant Recipients.

Reduction of cardiovascular death might have a significant effect on the long-term survival rates of renal transplant recipients (RTRs). The aim of the study was to assess the relation between arterial stiffness and graft function, adipose tissue content, and hydration status in patients after kidney transplantation (KTx).The study included 83 RTR patients (mean age: 55 ±â€Š13 years) who had been admitted to a nephrology-transplantation outpatient clinic 0.5 to 24 years after KTx. Clinical and laboratory data were analyzed and eGFR was calculated with the CKD-EPI formula. Arterial stiffness was assessed in all RTRs with pulse wave propagation velocity (PWV) with the use of a complior device. In addition, fluid and nutritional status was assessed with a Tanita BC 418 body composition analyzer. The control group consisted of 31 hospital workers who received no medication and had no history of cardiovascular disease.Multivariable linear regression analysis, with PWV as a dependent variable, retained the following independent predictors in the final regression model: red blood cell distribution width (RDW) (B = 0.323; P = 0.004), age (B = 0.297; P = 0.005), tacrolimus therapy (B = -0.286; P = 0.004), and central DBP (B = 0.185; P = 0.041). Multivariable linear regression analysis with eGFR as a dependent variable retained the following independent predictors in the final regression model; creatinine concentration (B = -0.632; P = 0.000), hemoglobin (B = 0.280; P = 0.000), CRP (B = -0.172; P = 0.011), tacrolimus therapy (B = 0.142; P = 0.039), and triglycerides (B = -0.142; P = 0.035).Our data indicates that: kidney transplant recipients can present modifiable CVD risk factors linked to increased arterial stiffness, DBP, waist circumference, SCr, time on dialysis, CyA therapy, and visceral fat mass; RDW is a parameter associated with arterial stiffness; and parameters such as CyA therapy, time on dialysis, PWV, RDW, and triglycerides show negative associations with the allograft function assessed with eGFR.