A review of ferric citrate clinical studies, and the rationale and design of the Ferric Citrate and Chronic Kidney Disease in Children (FIT4KiD) trial.

Pediatric chronic kidney disease (CKD) is characterized by many co-morbidities, including impaired growth and development, CKD-mineral and bone disorder, anemia, dysregulated iron metabolism, and cardiovascular disease. In pediatric CKD cohorts, higher circulating concentrations of fibroblast growth factor 23 (FGF23) are associated with some of these adverse clinical outcomes, including CKD progression and left ventricular hypertrophy. It is hypothesized that lowering FGF23 levels will reduce the risk of these events and improve clinical outcomes. Reducing FGF23 levels in CKD may be accomplished by targeting two key stimuli of FGF23 production-dietary phosphate absorption and iron deficiency. Ferric citrate is approved for use as an enteral phosphate binder and iron replacement product in adults with CKD. Clinical trials in adult CKD cohorts have also demonstrated that ferric citrate decreases circulating FGF23 concentrations. This review outlines the possible deleterious effects of excess FGF23 in CKD, summarizes data from the adult CKD clinical trials of ferric citrate, and presents the Ferric Citrate and Chronic Kidney Disease in Children (FIT4KiD) study, a randomized, placebo-controlled trial to evaluate the effects of ferric citrate on FGF23 in pediatric patients with CKD stages 3-4 (ClinicalTrials.gov Identifier NCT04741646).

Weight loss normalizes enhanced expression of the oncogene survivin in visceral adipose tissue and blood leukocytes from individuals with obesity.

BACKGROUND/OBJECTIVES: Survivin is an oncogene associated with a decrease in apoptosis, an increase in tumor growth, and poor clinical outcome of diverse malignancies. A correlation between obesity, cancer, and survivin is reported in the literature. To date, the impact of weight loss on change in survivin levels is understudied. This study was aimed at: (1) comparing survivin levels in adipose tissue (AT) from lean and obese animal models and evaluating changes after weight loss induced by energy restriction and/or exercise; (2) comparing survivin levels in normal weighted and obese humans and evaluating changes in survivin levels after weight loss induced by a very-low-calorie ketogenic diet (VLCKD) or bariatric surgery in AT and/or blood leukocytes (PBL/PBMCs). SUBJECTS/METHODS: Survivin expression was evaluated in subcutaneous (SAT) and visceral (VAT) AT derived from animal models of monogenic (Zucker rats) and diet-induced obesity (Sprague Dawley rats and C57BL/6J mice) and after a 4-week weight-loss protocol of energy restriction and/or exercise. Plasma was used to measure the inflammatory status. Survivin expression was also evaluated in PBMCs from patients with obesity and compared with normal weight, in PBLs after VLCKD, and in SAT and/or PBLs after bariatric surgery. RESULTS: Survivin expression was specifically higher in VAT from obese that lean animals, without differences in SAT. It decreased after weight loss induced by energy restriction and correlated with adiposity and inflammatory markers. In humans, the correlation between being obese and higher levels of survivin was confirmed. In obese subjects, survivin levels were reduced following weight loss after either VLCKD or bariatric surgery. Particularly, a decrease in PBMCs expression (not in SAT one) was found after surgery. CONCLUSIONS: Weight loss is effective in decreasing survivin levels. Also, PBL/PBMC should be regarded as appropriate mirror of survivin levels in VAT for the identification of an obesity-related protumoral microenvironment.

Epidemiological Aspects of Maternal and Congenital Toxoplasmosis in Panama.

In Panama, epidemiological data on congenital toxoplasmosis are limited, making it difficult to understand the scope of clinical manifestations in the population and factors that may increase the risk of infection. This study provides insight into the epidemiological situation of maternal and congenital toxoplasmosis in Panama and contributing information on the burden of this disease in Central America. Blood samples were collected from 2326 pregnant women and used for the detection of anti-T. gondii antibodies. A high seroprevalence (44.41%) was observed for T. gondii infection in pregnant women from different regions of Panama, with an estimated incidence rate of congenital toxoplasmosis of 3.8 cases per 1000 live births. The main risk factors associated with T. gondii infection using bivariate statistical analysis were an elementary level education and maternal age range of 34-45 years. Multivariate statistical analyses revealed that in some regions (San Miguelito, North and West regions), the number of positive cases correlated with the presence of pets, stray dogs and the consumption of poultry. In other regions (East and Metropolitan regions), the absence of pets was considered a protective factor associated with negative cases, while the presence of stray cats and the age range of 25-34 years did not represent any risk in these regions.

[Multidisciplinary methodology and ketogenic diet in real clinical practice: efficacy and rapidity in weight loss. Survival Analysis PROMET Lipoinflammation study]. / Metodología multidisciplinar y dieta cetogénica en la práctica clínica real: eficacia y rapidez en la pérdida de peso. Análisis de supervivencia. Estudio PROMET Lipoinflamación.

INTRODUCTION: Objective: the aim of the current work was to evaluate the response time to a method of weight loss that includes dietary guidelines, physical exercise and emotional support. The response was defined as a loss of 10% of the baseline weight. Methods: data was obtained from the patients' record recruited in Promet Lipoinflamación, an observational study of real world data in obese or overweight patients treated with a multidisciplinary method and based initially on a very-low-calorie ketogenic (VLCK) diet. Weight loss rate was evaluated through a survival analysis Kaplan-Meier and related factors through Cox regression). Results: 6,369 subjects were included and 74.4% managed to reach a weight loss of 10% in a mean time of 57.64 days (IC 95%: 56.95-58.33). The factors associated with a greater probability of reaching a loss of 10% or more were male gender (RR: 1.37, p < 0.001), obesity types I, II and III vs. overweight (RR: 1.24, p < 0.001, 1.26, p < 0.001 and 1.22, p < 0.001, respectively) and young age vs. more than 55 years old (RR: 2.17, p < 0.001). Conclusion: Results obtained through real clinical practice show that the method produces fast and intense weight loss. Three out of four patients lost at least 10% of body weight in an average of 58 days.

INTRODUCCIÓN: Objetivo: el objetivo del estudio fue evaluar el tiempo de respuesta, definido como pérdida del 10% del peso, al tratamiento con un método multidisciplinar de pérdida de peso que incluye dieta (inicialmente cetogénica), ejercicio físico y soporte emocional. Métodos: los datos se obtuvieron a partir del registro de pacientes reclutados en el estudio Promet Lipoinflamación, un estudio observacional de práctica clínica real en pacientes obesos o con sobrepeso tratados con el método multidisciplinar, basado inicialmente en una dieta cetogénica de muy bajas calorías. La velocidad se valoró mediante un análisis de supervivencia Kaplan-Meier y los factores asociados mediante regresión de Cox. Resultados: la muestra estudiada fue de 6369 sujetos. El 74,4% consiguió alcanzar una pérdida de peso del 10% en una media de tiempo de 57,64 días (IC 95%: 56,95-58,33]. Los factores asociados a mayor probabilidad de alcanzar pérdida del 10% o más fueron género masculino (RR: 1,37; p < 0,001), obesidad de tipos I, II y III frente a sobrepeso (RR: 1,24; p < 0,001; 1,26; p < 0,001 y 1,22; p < 0,001, respectivamente) y edad joven frente a mayor de 55 años (RR: 2,17; p < 0,001). Conclusiones: los resultados obtenidos a través de la práctica clínica real muestran que el método produce una pérdida de peso rápida e intensa. Tres de cada cuatro pacientes perdieron, como mínimo, el 10% del peso corporal en una media de 58 días.

Efficacy of a 2-Month Very Low-Calorie Ketogenic Diet (VLCKD) Compared to a Standard Low-Calorie Diet in Reducing Visceral and Liver Fat Accumulation in Patients With Obesity.

Background: Currently the treatment of non-alcoholic fatty liver disease (NAFLD) is based on weight loss through lifestyle changes, such as exercise combined with calorie-restricted dieting. Objectives: To assess the effects of a commercially available weight loss program based on a very low-calorie ketogenic diet (VLCKD) on visceral adipose tissue (VAT) and liver fat content compared to a standard low-calorie (LC) diet. As a secondary aim, we evaluated the effect on liver stiffness measurements. Methods: Open, randomized controlled, prospective pilot study. Patients were randomized and treated either with an LC or a VLCKD and received orientation and encouragement to physical activity equally for both groups. VAT, liver fat fraction, and liver stiffness were measured at baseline and after 2 months of treatment using magnetic resonance imaging. Paired t-tests were used for comparison of continuous variables between visits and unpaired test between groups. Categorical variables were compared using the χ2-test. Pearson correlation was used to assess the association between VAT, anthropometric measures, and hepatic fat fraction. A significance level of the results was established at p < 0.05. Results: Thirty-nine patients (20 with VLCKD and 19 with LC) were evaluated at baseline and 2 months of intervention. Relative weight loss at 2 months was -9.59 ± 2.87% in the VLCKD group and -1.87 ± 2.4% in the LC group (p < 0.001). Mean reductions in VAT were -32.0 cm2 for VLCKD group and -12.58 cm2 for LC group (p < 0.05). Reductions in liver fat fraction were significantly more pronounced in the VLCKD group than in the LC group (4.77 vs. 0.79%; p < 0.005). Conclusion: Patients undergoing a VLCKD achieved superior weight loss, with significant VAT and liver fat fraction reductions when compared to the standard LC diet. The weight loss and rapid mobilization of liver fat demonstrated with VLCKD could serve as an effective alternative for the treatment of NAFLD. Clinical Trial Registration: ClinicalTrials.gov, identifier: NCT04322110.

Structural Changes of Subcutaneous Tissue Valued by Ultrasonography in Patients with Cellulitis Following Treatment with the PnKCelulitis® Program.

Background: Poor eating habits, a sedentary lifestyle, and limited physical activity are predisposing factors for the development of cellulite. The PnKCelulitis® Programme (Pronokal Group, Barcelona, Spain) is a new approach to the treatment of cellulite that combines dietary guidelines, physical exercise, and the application of an anti-cellulite cream. Objective: We sought to objectively and via cutaneous ultrasound assess the benefit of the new multidisciplinary anti-cellulite treatment program and to evaluate any visual changes in the appearance of the skin. Materials and methods: Twenty women with Grades 1 to 3 cellulite were included in the study. All women underwent the multidisciplinary treatment. Clinical controls assessed the evolution of the degree of cellulite; the anthropometric parameters (e.g., weight, body mass index, and mean and low abdominal circumference) and body composition were assessed by bioimpedance. Ultrasound assessments were performed blinded at the beginning and at the end of treatment to assess the following: thickness of the skin, dermis, and hypodermis; areas of indentation; and changes in the echogenicity of the dermis. Results: The degree of cellulite was reduced in all locations, and 90 percent (18/20) of the sample saw their cellulite reduced by at least one degree. Cellulite in the abdomen disappeared in all of the women who had initially presented with it. Most of the subjects with cellulite in the buttocks (70%, 13/19) completed the treatment with Grade 0. There was a decrease in weight and a reduction of abdominal perimeters at the expense of only body fat. Significant decreases in the thickness of the skin and hypodermis and in areas of indentation were observed (p<0.05), in addition to an increase in the echogenicity of the dermis in 18 of the 20 patients. Conclusions: The multidisciplinary treatment program evaluated in this study appears to be an effective and safe treatment for patients with different degrees of cellulite, both clinically and via ultrasound imaging. Additional research with a larger patient cohort is needed to support our findings.

Effect of postnatal maternal protein intake on prenatal programming of hypertension.

This study examined whether postnatal maternal dietary protein deprivation during the time of nursing can program hypertension when the offspring are studied as adults. Rats were fed either a 6% or 20% protein diet during the second half of pregnancy and continued on the same diet while rats were nursing their pups. The neonates of all of the rats were cross-fostered to a different mother and studied as adults. Adult rats that had a normal prenatal environment but were reared by mothers fed a low-protein diet until weaning (20%-6%) were hypertensive, had a higher renal Na(+)-K(+)-2Cl(-) cotransporter (NKCC2) and Na(+)-Cl(-) cotransporter (NCC) protein abundance yet a comparable number of glomeruli, and had higher plasma renin and angiotensin II levels compared to control (20%-20%). Rats whose mothers were fed a 6% protein diet and cross-fostered to a different rat fed a 6% protein diet until weaning (6%-6%) were hypertensive, had elevated plasma renin and angiotensin II levels, and had a reduction in nephron number but had NKCC2 and NCC levels comparable to 20% to 20% offspring. The 6% to 20% had blood pressure and glomerular numbers comparable to 20% to 20% rats. The hypertension resulting from prenatal dietary protein deprivation can be normalized by improving the postnatal environment. Combined prenatal and postnatal maternal dietary protein deprivation and maternal dietary protein deprivation while nursing alone (20%-6%) results in hypertension, but the mechanism for the hypertension in these groups is different.