Research trends on the gut microbiota in endocrine metabolism: a thematic and bibliometric analysis.

Background: Gut microbiota studies in the field of endocrinology metabolism have attracted increasing attention in recent years. To comprehensively assess the evolving landscape of this research field, we conducted a thorough bibliometric analysis of gut microbiota studies in endocrinology metabolism indexed in the Web of Science database. Methods: We collected and analyzed 3,339 original research articles and reviews published from 1972 to 2023. Using various bibliometric indicators, we investigated publication trends, country contributions, international collaborations, prolific authors, top journals, and influential articles. Results: Our analysis revealed a significant upsurge in publications after 2010, indicating a growing scientific interest in microbiota and endocrinology metabolism. Keyword and thematic analyses have identified gut microbiota, obesity, diabetes, and inflammation as core research themes. Additionally, the roles of probiotics and prebiotics are increasingly researched for their therapeutic effects in shaping the microbiota. Conclusion: This study reveals that research in endocrinology metabolism is increasingly decoding the connection between gut microbiota and diseases. There's also a growing focus on microbiota manipulation, which points to a shift towards personalized medicine. Future research should focus on integrating these findings into clinical practice, moving from lab-based studies to real-world patient care.

Revised one-bag IV fluid protocol for pediatric DKA: a feasible approach and retrospective comparative study.

BACKGROUND: This study compared the effectiveness of the traditional and revised one-bag protocols for pediatric diabetic ketoacidosis (DKA) management. METHODS: This single-center retrospective cohort study included children diagnosed with DKA upon admission between 2012 and 2019. Our institution reevaluated and streamlined the traditional one-bag protocol (revised one-bag protocol). The revised one-bag protocol rehydrated all pediatric DKA patients with dextrose (5 g/100 ml) containing 0.45% NaCl at a rate of 3500 ml/m2 per 24 h after the first 1 h bolus of normal saline, regardless of age or degree of dehydration. This study examined acidosis recovery times and the frequency of healthcare provider interventions to maintain stable blood glucose levels. RESULTS: The revised one-bag protocol demonstrated a significantly shorter time to acidosis recovery than the traditional protocol (12.67 and 18.20 h, respectively; p < 0.001). The revised protocol group required fewer interventions for blood glucose control, with an average of 0.25 dextrose concentration change orders per patient, compared to 1.42 in the traditional protocol group (p < 0.001). Insulin rate adjustments were fewer in the revised protocol group, averaging 0.52 changes per patient, vs. 2.32 changes in the traditional protocol group (p < 0.001). CONCLUSION: The revised one-bag protocol for pediatric DKA is both practical and effective. This modified DKA management achieved acidosis recovery more quickly and reduced blood glucose fluctuations compared with the traditional one-bag protocol. Future studies, including randomized controlled trials, should assess the safety and effectiveness of the revised protocol in a broad range of pediatric patients with DKA.

Genetic influence on urinary vitamin D binding protein excretion and serum levels: a focus on rs4588 C>A polymorphism in the GC gene.

Introduction: Vitamin D binding protein (VDBP) plays a crucial role in vitamin D transport and metabolism. The rs4588-A polymorphism of the GC gene, encoding VDBP, has been associated with altered serum VDBP and 25-hydroxyvitamin D (25OHD) levels. However, the mechanisms underlying these effects remain unclear. We aimed to investigate the relationship between urinary VDBP excretion and serum VDBP and 25OHD levels in individuals with and without the rs4588-A allele. Methods: A cross-sectional study was conducted on 109 children (mean age: 11.96 years) to explore the impact of rs4588-A on vitamin D metabolism and urinary VDBP excretion. Biochemical analyses determined serum 25OHD and VDBP levels, and urinary VDBP-to-creatinine ratio (u-VDBP/Cr). Genotyping for rs4588 SNP was performed using LightSNiP assay. Statistical analyses included correlation, linear regression, and comparison between allele groups. Results: Participants carrying the rs4588-A allele exhibited lower serum 25OHD levels compared to non-carriers (median (IQR): 11.85 (3.5) vs. 12.86 (4.9), p = 0.023). However, no statistically significant differences were observed in serum VDBP levels (126.34 ± 59.3 in rs4588-A vs. 136.49 ± 51.3 in non-rs4588-A, p = 0.141) or in u-VDBP/Cr (median (IQR): 0.4 (0.35) in rs4588-A vs. 0.386 (0.43) in non-rs4588-A, p = 0.189) between the two allele groups. A significant inverse correlation between u-VDBP/Cr and serum VDBP levels was found only in rs4588-A carriers (r = -0.367, p = 0.024). No such correlation was observed in non-carriers or the entire cohort. A linear regression analysis confirmed the impact of u-VDBP/Cr on serum VDBP levels in rs4588-A carriers (B = -0.269, t = -2.185, p = 0.035). Conclusion: Individuals with the rs4588-A allele in the GC gene had lower serum 25OHD levels. An inverse correlation between urinary VDBP excretion and serum VDBP levels was observed, suggesting a partial role of the renal pathway in altered serum VDBP and 25OHD levels linked to the rs4588-A allele.

The prevalence and prognostic effect of hyponatremia in children with COVID-19 pneumonia: a retrospective study.

BACKGROUND: The aim of the study was to examine the effect of hyponatremia at admission as a negative prognostic factor in children hospitalized with COVID-19 pneumonia. METHODS: The data of patients aged 1 month-18 years, who were followed with the diagnosis of pneumonia at Çanakkale Onsekiz Mart University Hospital, Department of Pediatrics, between January 2018 and May 2021 were examined, retrospectively. Patients (n=661) were divided into two main groups; COVID-19 pneumonia (n=158) and the other pneumonias [other viral pneumonia (n=161) and pneumonia of unknown etiology (n=342)]. RESULTS: Six hundred and twenty-three patients with a median (Q1-Q3) age of 4 (1.5-8) years, 59.4% of whom were male were included in the study. The overall prevalence of hyponatremia at admission was 11.2% and was lower in those with COVID-19 pneumonia than in those with other viral pneumonia (6.4% vs. 15.2%, p=0.013). When evaluated irrespective of their COVID-19 status, hyponatremic patients had a higher supplemental oxygen requirement (OR 2.5 [1.4-4.3], p < 0.001), higher need for intensive care unit (ICU) admission (OR 3.7 [1.3-10.2], p=0.009) and longer duration of hospitalization (p=0.016) than the normonatremic patients. In patients with COVID-19 pneumonia, being hyponatremic had no effect on supplemental oxygen requirements or the duration of hospitalization. When hyponatremic patients were evaluated, the supplemental oxygen requirements and duration of hospitalization of those with COVID-19 pneumonia were similar to the other pneumonias (p > 0.05 for all comparisons). However, normonatremic COVID-19 pneumonias had higher supplemental oxygen requirements than other viral pneumonias and pneumonia of unknown etiology (OR 4.7 [2.2-10.3], p < 0.001; OR 1.6 [1 -2.7], p=0.043, respectively). CONCLUSION: This study found that hyponatremia at admission is rarer in children with COVID-19 pneumonia than other viral pneumonias and has no effect on supplemental oxygen requirements or the duration of hospitalization.

Steroid Hormone Profiles and Molecular Diagnostic Tools in Pediatric Patients With non-CAH Primary Adrenal Insufficiency.

CONTEXT: There is a significant challenge of attributing specific diagnoses to patients with primary adrenal insufficiency of unknown etiology other than congenital adrenal hyperplasia (non-CAH PAI). Specific diagnoses per se may guide personalized treatment or may illuminate pathophysiology. OBJECTIVE: This work aimed to investigate the efficacy of steroid hormone profiles and high-throughput sequencing methods in establishing the etiology in non-CAH PAI of unknown origin. METHODS: Pediatric patients with non-CAH PAI whose etiology could not be established by clinical and biochemical characteristics were enrolled. Genetic analysis was performed using targeted-gene panel sequencing (TPS) and whole-exome sequencing (WES). Plasma adrenal steroids were quantified by liquid chromatography-mass spectrometry and compared to that of controls. This study comprised 18 pediatric endocrinology clinics with 41 patients (17 girls, median age: 3 mo, range: 0-8 y) with non-CAH PAI of unknown etiology. RESULTS: A genetic diagnosis was obtained in 29 (70.7%) patients by TPS. Further molecular diagnosis could not be achieved by WES. Compared to a healthy control group, patients showed lower steroid concentrations, most statistically significantly in cortisone, cortisol, and corticosterone (P < .0001, area under the receiver operating characteristic curve: .96, .88, and .87, respectively). Plasma cortisol of less than 4 ng/mL, cortisone of less than 11 ng/mL, and corticosterone of less than 0.11 ng/mL had a greater than 95% specificity to ensure the diagnosis of non-CAH PAI of unknown etiology. CONCLUSION: Steroid hormone profiles are highly sensitive for the diagnosis of non-CAH PAI of unknown etiology, but they are unlikely to point to a specific molecular diagnosis. TPS is an optimal approach in the molecular diagnosis of these patients with high efficacy, whereas little additional benefit is expected from WES.

A new entity in the NARS2 variant: the first reported case of type 1 diabetes mellitus associated with the phenotype.

NARS2 mutations are known to cause various clinical phenotypes such as nonsyndromic hearing loss, Leigh/Alpers syndrome, refractory epilepsy, developmental delay, intellectual disability and myopathy. We presented the first Turkish variant of NASR2 and added type 1 diabetes mellitus (DM), which was not previously described in the phenotype spectrum of this disease. A 4.5-month-old girl presented with hearing loss, hypotonia, refractory myoclonic epilepsy, severe developmental delay and large subdural hemorrhage. In the first year of the follow-up, type 1 DM developed. A homozygous missense mutation, [c.500 A>G, p.H167R] in the NARS2 gene was detected in the trio-based whole-exome sequencing (WES). In this disease, in addition to multi-organ involvement, type 1 DM may also develop, as in our case. Since it is a mitochondrial disease, the decision to treat with valproic acid should be reconsidered. The long diagnostic process can be shortened with WES.

Novel MTTP Gene Mutation in a Case of Abetalipoproteinemia with Central Hypothyroidism

Abetalipoproteinaemia (ABL) is an autosomal recessive disorder characterized by very low plasma concentrations of total cholesterol and triglyceride (TG). It results from mutations in the gene encoding microsomal TG transfer protein (MTTP). A nine-month-old girl was admitted to hospital because of fever, cough, diarrhea and failure to thrive. She had low cholesterol and TG levels according to her age. The peripheral blood smear revealed acanthocytosis. Thyroid function test showed central hypothyroidism. Cranial magnetic resonance imaging revealed the retardation of myelination and pituitary gland height was 1.7 mm. A homozygous novel mutation [c.506A>T (p.D169V)] was detected in the MTTP gene. Vitamins A, D, E, and K and levothyroxine were started. The coexistence of ABL and central hypothyroidism has not previously been reported. A homozygous novel mutation [c.506A>T (p.D169V)] was detected in the MTTP gene.

Mutational analysis of PHEX, FGF23 and CLCN5 in patients with hypophosphataemic rickets.

CONTEXT: Hypophosphataemic rickets (HR) is a group of rare hereditary renal phosphate wasting disorders caused by mutations in PHEX, FGF23, DMP1, ENPP1, CLCN5 or SLC34A3. OBJECTIVE: To investigate underlying genetic defects in patients with hypophosphataemic rickets. METHODS: We analysed genomic DNA from nine unrelated families for mutations in the entire coding region of PHEX, FGF23, DMP1, ENPP1, CLCN5 or SLC34A3 by PCR sequencing and copy number analysis. RESULTS: A total of 14 patients were studied. PHEX mutations were identified in 12 patients from seven families. Five of them were novel mutations present in eight patients: c.154G>T (p.E52*), c.401_402insGCCAAA (p.Q134_K135insPK), c.1600C>T (p.P534S), g.22016715_22056805del (40-kb deletion including promoter and exons 1-3) and c.2242_2243delCT (p.L748 fs*48). Four patients had previously reported mutations: c.1768+1G>A and c.1807G>A (p.W602*). Novel CLCN5 (c.1205G>A, p.W402*) and FGF23 (c.526C>G, p.R176G) mutations were found in two patients from the remaining two families. Many of the mutations were de novo: c.154G>T and c.2242_2243delCT in PHEX and c.526C>G in FGF23. Furthermore, we characterized the breakpoint of the novel PHEX g.22016715_22056805del and the c.2242_2243delCT, which is 6 bp from the stop codon, resulting in a frameshift and extension of the reading frame by 42 amino acids. CONCLUSIONS: Novel and de novo mutations are frequent and PHEX mutations are still the most common genetic defects in the Turkish population. Gene copy number analysis should be considered in patients with negative results by conventional PCR-based sequencing analysis. The current study further expands the mutation spectrum underlying HR.

An essential splice site mutation (c.317+1G>A) in the TSHR gene leads to severe thyroid dysgenesis.

Congenital hypothyroidism (CH) is the most common neonatal endocrine disorder and 2% of cases have familial origin. Our aim in this study was to determine the genetic alterations in two siblings with CH coming from a consanguineous family. Because CH is often inherited in autosomal recessive manner in consanguineous/multicase-families, we first performed genetic linkage studies to all known causative CH loci followed by conventional sequencing of the linked gene. The family showed potential linkage to the TSHR locus, and we detected an essential splice site mutation (c.317+1G>A) in both siblings. RT-PCR analysis confirmed the functionality of the mutation. The mutation was homozygous in the cases whereas heterozygous in carrier parents and an unaffected sibling. Here we conclude that thyroid agenesis in both siblings in this study originates from c.317+1G>A splice site mutation in the TSHR gene, and this study underlines the importance of detailed molecular genetic studies in the definitive diagnosis and classification of CH.

Hemoglobin cut-off values in healthy Turkish infants.

BACKGROUND: Anemia is a widespread public health problem associated with an increased risk of morbidity and mortality. This study was undertaken to determine the cut-off value of hemoglobin for infant anemia. METHODS: A cross-sectional retrospective study was carried out at well-baby clinics of a tertiary care hospital. A total of 1484 healthy infants aged between 4 to 24 months were included in the study. The relationship of hemoglobin (Hb) levels with mother age, birth weight, weight gain rate, feeding, and gender was evaluated. RESULTS: The Hb levels were assessed in four age groups (4 months, 6 months, 9-12 months, and 15-24 months) and the cut-off values of Hb were determined. Hb cut-off values (5th percentile for age) were detected as 97 g/L and 93 g/L at 4 months and 6 months, respectively. In older infants, the 5th percentile was 90.5 g/L and 93.4 g/L at 9-12 months and 15-24 months, respectively. The two values were lower than the World Health Organization criteria for anemia, which could partly due to the lack of information on iron status in our population. However, this difference highlights the need for further studies on normal Hb levels in healthy infants in developing countries. Hb levels of females were higher in all age groups; however, a statistically significant difference was found in gender in only 6 month-old infants. No statistically significant difference was found among Hb levels, mother's age, birth weight, weight gain rate, and nutritional status. CONCLUSION: Hb cut-off values in infants should be re-evaluated and be compatible with growth and development of children in that community.