Search Results (77)

Brain organoid technology has revolutionized in vitro modeling of human neurodevelopment and disease, providing unprecedented insights into cortical patterning, neural circuit assembly, and pathogenic mechanisms of neurological disorders. Critically, human brain organoids uniquely recapitulate human-specific developmental processes—such as the expansion of outer radial glia and neuromelanin—that are absent in rodent models, making them indispensable for studying human brain evolution and dysfunction. However, a major bottleneck persists: Extended culture periods (≥6 months) are empirically required to achieve late-stage maturation markers like synaptic refinement, functional network plasticity, and gliogenesis. Yet prolonged conventional 3D culture exacerbates metabolic stress, hypoxia-induced necrosis, and microenvironmental instability, leading to asynchronous tissue maturation—electrophysiologically active superficial layers juxtaposed with degenerating cores. This immaturity/heterogeneity severely limits their utility in modeling adult-onset disorders (e.g., Alzheimer’s disease) and high-fidelity drug screening, as organoids fail to recapitulate postnatal transcriptional signatures or neurovascular interactions without bioengineering interventions. We summarize emerging strategies to decouple maturation milestones from rigid temporal frameworks, emphasizing the synergistic integration of chronological optimization (e.g., vascularized co-cultures) and active bioengineering accelerators (e.g., electrical stimulation and microfluidics). By bridging biological timelines with scalable engineering, this review charts a roadmap to generate translationally relevant, functionally mature brain organoids. Full article

Background: BDE-47, a pervasive environmental pollutant detected in >90% of human serum samples, is increasingly linked to metabolic disorders. This study investigates the specific impact of BDE-47 exposure on the gut microbiota in prediabetic mice and evaluates the efficacy of therapeutic interventions in mitigating these effects. Objectives: To determine whether BDE-47 exposure induces diabetogenic dysbiosis in prediabetic mice and to assess whether dietary interventions, such as grape exosomes and an antioxidant cocktail, can restore a healthy microbiota composition and mitigate diabetes risk. Methods: In this study, a prediabetic mouse model was established in 54 male SPF-grade C57BL/6J mice through a combination of high-sugar and high-fat diet feeding with streptozotocin injection. Oral glucose tolerance tests (OGTT) were conducted on day 7 and day 21 post-modeling to assess the establishment of the model. The criteria for successful model induction were defined as fasting blood glucose levels below 7.8 mmol/L and 2 h postprandial glucose levels between 7.8 and 11.1 mmol/L. Following confirmation of model success, a 3 × 3 factorial design was applied to allocate the experimental animals into groups based on two independent factors: BDE-47 exposure and exosome intervention. The BDE-47 exposure factor consisted of three dose levels—none, high-dose, and medium-dose—while the exosome intervention factor included three modalities—none, Antioxidant Nutrients Intervention, and Grape Exosomes Intervention. Fresh fecal samples were collected from mice two days prior to sacrifice. Cecal contents and segments of the small intestine were collected and transferred into 1.5 mL cryotubes. All sequences were clustered into operational taxonomic units (OTUs) based on defined similarity thresholds. To compare means across multiple groups, a two-way analysis of variance (ANOVA) was employed. The significance level was predefined at α = 0.05, and p-values < 0.05 were considered statistically significant. Bar charts and line graphs were generated using GraphPad Prism version 9.0 software, while statistical analyses were performed using SPSS version 20.0 software. Results: The results of 16S rDNA sequencing analysis of the microbiome showed that there was no difference in the α diversity of the intestinal microbiota in each group of mice (p > 0.05), but there was a difference in the Beta diversity (p < 0.05). At the gate level, the abundances of Proteobacteria, Campylobacterota, Desulfobacterota, and Fusobacteriota in the medium-dose BDE-7 group were higher than those in the model control group (p < 0.05). The abundance of Patellar bacteria was lower than that of the model control group (p < 0.05). The abundances of Proteobacteria and Campylobacterota in the high-dose BDE-7 group were higher than those in the model control group (p < 0.05). The abundance of Planctomycetota and Patescibacteria was lower than that of the model control group (p < 0.05), while the abundance of Campylobacterota in the grape exosome group was higher than that of the model control group (p < 0.05). The abundance of Patescibacteria was lower than that of the model control group (p < 0.05), while the abundance of Firmicutes and Fusobacteriota in the antioxidant nutrient group was higher than that of the model control group (p < 0.05). However, the abundance of Verrucomicrobiota and Patescibacteria was lower than that of the model control group (p < 0.05). At the genus level, the abundances of Bacteroides and unclassified Lachnospiraceae in the high-dose BDE-7 group were higher than those in the model control group (p < 0.05). The abundance of Lachnospiraceae NK4A136_group and Lactobacillus was lower than that of the model control group (p < 0.05). The abundance of Veillonella and Helicobacter in the medium-dose BDE-7 group was higher than that in the model control group (p < 0.05), while the abundance of Lactobacillus was lower (p < 0.05). The abundance of genera such as Lentilactobacillus and Faecalibacterium in the grape exosome group was higher than that in the model control group (p < 0.05). The abundance of Alloprevotella and Bacteroides was lower than that of the model control group (p < 0.05). In the antioxidant nutrient group, the abundance of Lachnospiraceae and Hydrogenophaga was higher than that in the model control group (p < 0.05). However, the abundance of Akkermansia and Coriobacteriaceae UCG-002 was significantly lower than that of the model control group (p < 0.05). Conclusions: BDE-47 induces diabetogenic dysbiosis in prediabetic mice, which is reversible by dietary interventions. These findings suggest that microbiota-targeted strategies may effectively mitigate the diabetes risk associated with environmental pollutant exposure. Future studies should further explore the mechanisms underlying these microbiota changes and the long-term health benefits of such interventions. Full article

Background: Riboflavin transporter deficiency type 2 is an ultra-rare, yet treatable, inborn error of metabolism. This autosomal recessive disorder is caused by pathogenic mutations in the SLC52A2 gene leading to progressive ataxia, polyneuropathy, and hearing and visual impairment. The early initiation of riboflavin therapy can prevent or mitigate the complications. To date, only 200 cases have been reported, mostly in consanguineous populations. The p.Gly306Arg founder mutation, identified in patients of Lebanese descent, is the most frequently reported worldwide. It was described in a homozygous state in a total of 21 patients. Therefore, studies characterizing the phenotypic spectrum of this mutation remain scarce. Methods: A retrospective review of charts of patients diagnosed with riboflavin transporter deficiency type 2 at a tertiary-care reference center in Lebanon was performed. Clinical, biochemical, and molecular profiles were analyzed and compared to reported cases in the literature. Results: A total of six patients from three unrelated families were diagnosed between 2018 and 2023. All patients exhibited the homozygous founder mutation, p.Gly306Arg, with variable phenotypes, even among family members. The median age of onset was 3 years. Diagnosis was achieved by exome sequencing at a median age of 5 years, as clinical and biochemical profiles were inconsistently suggestive. The response to riboflavin was variable. One patient treated with high-dose riboflavin recovered his motor function, while the others were stabilized. Conclusions: This study expands the current knowledge of the phenotypic spectrum associated with the p.Gly306Arg mutation in the SLC52A2 gene. Increased awareness among physicians of the common manifestations of this rare disorder is crucial for early diagnosis and treatment. In the absence of a consistent clinical or biochemical phenotype, the use of next-generation sequencing as a first-tier diagnostic test may be considered. Full article

Background/Objectives: Narcolepsy was first described in the late 19th century, and in the current decade, narcolepsy patients are reaching their senior years. Little is known about the evolution of clinical features, the management of narcolepsy medications, and the development of comorbid conditions. We aimed to present the clinical characteristics, comorbidities, and therapeutic choices of seniors with narcolepsy. Methods: We extracted 21 charts of patients older than 65 with a diagnosis of narcolepsy according to the International Classification of Sleep Disorders Third Edition. We reviewed and analyzed all clinical and available polysomnographic data. Results: A total of 21 patients (median age 69 years. 67.0–71.0 interquartile range IQR; 71% female) were included. Three (14.3%) had type I and 18 (85.7%) had type II narcolepsy. The average age at symptom onset was 23 years (IQR 19.5–27.5). Diagnosis was made at an average age of 41 years (IQR 33–45), between 1990 and 2002. Median time from onset to diagnosis was 13.7 years (IQR 9.5–19). The most prevalent cardiovascular/metabolic comorbidity was hypertension (57.1%). All patients were historically using narcolepsy medications. Fewer patients were currently on wake-promoting agents (85.7%), with over half on modafinil (55.6%). None currently reported the need to nap during the daytime. Conclusions: Narcolepsy is a lifelong, but not progressive disorder, that has yet to be well-characterized in the senior population. A few seniors appear to outgrow the disorder and to no longer need wake-promoting agents. It is important to consider cardiometabolic comorbidities in the management of narcolepsy in this population. Geriatricians should be educated on narcolepsy with specific programs for these seniors. Full article

Background/Objective: Condyloma acuminatum, also known as genital warts, results from infections of the basal epithelium or mucous membranes by human papillomavirus (HPV). These lesions can significantly impact patients’ quality of life. Recent advances in laser technology, particularly ablative lasers such as CO₂ and Erbium–YAG (Er:YAG), have introduced new treatment opportunities. The Er:YAG laser has gained recognition as a safe and effective treatment for viral warts. This study aimed to evaluate the efficacy of Er:YAG laser treatment of male genital warts and to identify risk factors that might influence its effectiveness. Methods: A retrospective chart review of 102 patients who underwent Er:YAG laser wart removal between January 2019 and April 2024 was conducted. Results: Of the 102 patients, 61 (60%) achieved complete response by the 12-month follow-up visit. The response rates were significantly lower when there was a high number of sessions required for complete response, long duration between wart onset and laser treatment, high number of warts treated, positive smoking status, concurrent immunosuppressed state, or active metabolic disease. Conclusions: The Er:YAG laser is an effective method for treating recalcitrant warts. Various factors were shown to influence its efficacy. Full article

Background: Adenotonsillectomy (AT) is a common surgical procedure among pediatrics, usually performed to treat obstructive sleep apnea (OSA), recurrent tonsillitis, and chronic adenoid hypertrophy. The aim of our systematic review is to evaluate the relationship between AT and postoperative weight gain in children to guide clinicians in optimizing surgical outcomes. Methods: A systematic search was conducted following the PRISMA guidelines in PubMed, MEDLINE, and Web of Science databases. Studies evaluating weight, BMI, and growth parameters before and after AT were included. Data were collaboratively extracted, including patient demographics, baseline weight status, comorbidities, and long-term outcomes. Results: Underweight children (less than the 3rd percentile on the growth chart) who underwent AT often experienced “catch-up growth” in weight, while obese children (above the 95th percentile on the growth chart) had postoperative weight gain that exacerbated pre-existing obesity. These outcomes were affected by factors such as baseline weight, age, and comorbid conditions. Conclusions: AT can improve the quality of life in underweight children, while overweight or obese children need careful monitoring and nutrition counseling postoperatively to mitigate excessive weight gain. More randomized trials are needed to better understand the metabolic and growth implications of AT and to refine clinical guidelines. Full article

Background/Objectives: An increasing number of studies have reported liver involvement in both children and adults with celiac disease (CD). This often manifests as isolated hypertransaminasemia or hepatic steatosis (HS). The aim of this study was to define the prevalence of hypertransaminasemia and HS in a pediatric population with CD before starting a gluten-free diet (GFD) and to analyze how the introduction of a GFD could modify this condition. We also conducted a state-of-the-art literature review of the association between hypertransaminasemia, metabolic dysfunction-associated steatotic liver disease (MASLD) and CD. Methods: We retrospectively reviewed the clinical charts of pediatric CD patients diagnosed in three different pediatric units of Sicily, analyzing clinical, laboratory, ultrasound, and histology data before and 12 months after the introduction of a GFD. Results: A total of 160 patients (65.0% females, median age 6.4 (0.8–13.2) years) were included; hypertransaminasemia and HS prevalences at diagnosis were 8.1% and 6.1%, respectively. Subjects with hypertransaminasemia were younger (p = 0.01) than those without and had higher frequencies of HS (p = 0.034) and anti-tissue transglutaminase (tTg) immunoglobulin (Ig)G positivity (p = 0.046). Subjects with HS were younger (p = 0.0001) and had a higher frequency of hypertransaminasemia (p = 0.029) compared to non-steatotic ones. After 12 months of a GFD, hypertransaminasemia and HS persisted in 53.8% and 50.0% of patients, respectively. Conclusions: The prevalences of hypertransaminasemia and HS in Sicilian pediatric CD patients seem to be lower than those reported in other geographical areas. A GFD can reverse the trend of liver involvement, although periods of longer than 12 months may be necessary. However, a GFD has been associated with an increased prevalence of HS, and so regular follow-up involving a nutritionist should be recommended to guide physicians in patient management. Full article

The current study investigates the systemic effects of imidacloprid, one of the most widely used neonicotinoid insecticides, on the liver and gut microbiome of rats in detail. With consideration of recent discussions on the potential harmfulness of imidacloprid to environmental and human health, the aim was to investigate the influence of this compound in the framework of controlled exposure at different dosages, namely, IMI-5, IMI-10, and IMI-30. Histopathological examination showed that liver morphology changed significantly with the dose, including in terms of cellular disorganization and signs of stress, with an alteration in the hepatic architecture. Morphological changes were related to disturbances in the activity of liver enzymes, reflecting deteriorating liver function with increased imidacloprid exposure. In parallel with this, a deep analysis of the gut microbiome revealed dramatic changes in microbial diversity and composition. Alpha diversity, represented by the Chao1 and Shannon indices, was significantly reduced with an increased dosage of imidacloprid. Subsequent beta diversity analysis, as visualized by principal component analysis, showed distinct clustering among the microbial communities, separated well between control and imidacloprid-treated groups, especially at higher dosages. Taxonomic analysis revealed an increase in the Firmicutes/Bacteroidetes ratio and a change in key phyla including Actinobacteria, Bacteroidetes, and Verrucomicrobia. A heatmap and bar charts further confirmed dose-dependent changes in microbial abundance. These changes point toward imidacloprid-induced dysbiosis, a reduction in microbial diversity, and an imbalance in the F/B ratio, usually associated with metabolic disorders. Overall, given these findings, it would seem that imidacloprid does indeed impose serious negative impacts on both liver function and gut microbiota composition and may have further impacts on health and ecological safety. Full article

Background: Time-restricted eating (TRE) shows promise for managing weight and metabolic issues, yet its application in real-world healthcare settings remains underexplored. This study aims to assess the real-world utilisation and short-term outcomes of TRE in clinical practice. Methods: This observational study used a retrospective chart review of 271 adults who attended a metabolic specialist clinic between 2019 and 2023. Descriptive statistics and multivariable logistic regression were used to identify factors associated with TRE adoption, while paired sample t-tests evaluated changes in outcomes among those who received TRE advice. Results: Among the 271 patients, 76% were female, 90% Caucasian, and 94% overweight/obese. Of all patients, 47.2% received TRE advice, mainly using the 16:8 method, alongside additional dietary guidance for 60% of patients. Working status and baseline metabolic profiles were the only factors significantly associated with TRE adoption. Among those who followed TRE, 81% experienced modest but significant reductions in weight (−1.2 kg, p < 0.01), BMI (−0.4 kg/m², p < 0.01), and waist circumference (−3.7 cm, p < 0.01). Conclusions: This study highlights TRE as a feasible and practical dietary strategy for improving metabolic health in healthcare settings. However, further research and improved data capture are needed to explore long-term adherence, potential adverse effects, and the effectiveness of TRE across diverse patient populations. Full article

In this review, we provide an evidence-based approach to determine the cellular and systemic actions of two structurally similar flavonoids, apigenin and chrysin. We have clearly evaluated and charted the overlapping and diverging properties of these two sister flavonoids. Based on two separate Omics-based approaches by our group and independent reports from others, the cholesterol-lowering properties have been revealed. In addition, the prevention of uric acid biosynthesis and enhancement of ketogenesis have also been quite evident in these two flavonoids. Along with these overlapping functions, apigenin and chrysin have also demonstrated unique properties that allow them to stand out from each other. Chrysin has demonstrated abilities like downregulating alanine metabolism and pyrimidine synthesis, which could be helpful in metabolic diseases like cancer. In contrast, apigenin has demonstrated anti-oxidant and anti-inflammatory properties by enhancing endogenous anti-inflammatory lipids and upregulating vasoprotective metabolites, which could be beneficial for cardiovascular, renal, and cerebrovascular complications. Further validation studies using in vivo and translational approaches could provide us with better clarity regarding the use of these agents therapeutically and to treat a combination or pool of metabolic diseases. Full article

Background and Objectives: Type 2 diabetes (T2DM) affects millions across the globe, generating a veritable public health issue through quality-of-life-reducing chronic complications, among which urinary tract infections are the most common. A shift in the disease managing paradigm from a glucose-centered view to a concept of cardio-reno-metabolic health has uniquely placed SGLT2 inhibitors as viable medication for the complex management of T2DM and its comorbidities. Some concerns have been raised over the increased likelihood of urinary tract infections (UTIs) associated with SGLT2 inhibitor use. The current study aims to evaluate the risk of developing urinary tract infections if patients with type 2 diabetes take SGLT2 inhibitors and determine those factors which make these patients more prone to develop this undesired complication. Materials and Methods: A cross-sectional, noninterventional evaluation of 328 patients with type 2 diabetes consecutively admitted to the Diabetes Clinic of “Pius Brinzeu” County Emergency Hospital in Timisoara, between January and February of 2024, was performed by examining medical charts and running statistical analyses using MedCalc version 22.26.0.0. Results: There was no statistical difference between patients taking SGLT2 inhibitors and those taking other glucose lowering medications when examining the presence of UTIs. Those patients with a higher HbA1c or BMI showed an increased predisposition to contracting UTI. The female gender was also associated with an increased likelihood of UTI. A further evaluation of the sublot of patients taking SGLT2 inhibitors revealed that not only higher BMI or HbA1c could be a predictor for the likelihood of developing UTI, but also a longer duration of T2DM was a predisposing factor. Conclusions: The use of SGLT2 inhibitors did not increase the likelihood of developing a urinary tract infection in this patient population. Full article

Background: Diabetes mellitus (DM) is one of the most impactful health problems worldwide. It affects ocular health in multiple ways and is one of the leading causes of vision loss. Our study aimed to evaluate the most important systemic risk factors related to the occurrence of cataracts in patients with DM. Method: This study evaluated a final number of 319 participants who were previously diagnosed with DM. For all patients, we retrieved data regarding DM status, metabolic control, demographic and anthropometric indices, and generally associated comorbidities from their medical charts. A comprehensive eye examination was performed on all patients. Results: The main studied risk factors were hypertension, cardiovascular disease (CVD), chronic kidney disease (CKD), diabetic polyneuropathy (DPN), dyslipidemia, and hepatic steatosis, which were present among the entire population. Hypertension (67.6%), DPN (53.3%), and dyslipidemia (46.6%) were highly prevalent in the cataract subgroup, and CKD (p < 0.001) and DPN (p = 0.019) were found to be predictive factors for the probability of cataract occurrence. Ophthalmologic evaluation was used to assess the presence of ocular complications, such as diabetic retinopathy (DR) and diabetic maculopathy. DR reached statistically significant values in the occurence of cataracts. Patients’ age and DM-related factors, such as disease duration (p < 0.001) and HbA1c values (p = 0.029), significantly increased the risk of cataracts. Smoking was self-reported by 24.8% of the patients, with a significant impact on the occurrence of cataracts (p = 0.04). Conclusions: Patients with DM who exhibit a longer disease duration and poor glycemic control in conjunction with systemic comorbidities present a higher risk of developing cataracts; consequently, a strict therapeutic approach regarding these risk factors is needed. Full article

Background: Cardiovascular diseases (CVDs) and chronic kidney disease (CKD) are common causes of morbidity and mortality. However, the impact of changes in lifestyle and rehabilitation programs on the progression of cardiovascular, renal, and metabolic (CRM) conditions, remains unclear. Methods: In a retrospective manner, we analyzed charts of 200 patients admitted for cardiorespiratory rehabilitation at our facility in 2023. A 6 min walk test, echocardiographic features, and laboratory values were investigated to evaluate the impact of cardiorespiratory rehabilitation in patients post cardiac surgery. This study examined the impact of combined lifestyle and exercise scores (diet, alcohol consumption, smoking, aerobic physical activity, sedentary behavior, sleep duration, and social connection) on cardio–renal–metabolic profiles and on a quality-of-life score measured by the Borg Scale. Results: During the rehabilitation program, left ventricular ejection fraction (LVEF) significantly increased (51.2 vs. 54.3%, SEM 0.51 p = 0.001). The six-minute walk test (6 MWT) significantly improved in terms of meters (133 vs. 373 m, SEM 6.41, p < 0.001) and Borg scale (6.6 vs. 2.5, SEM 0.06, p < 0.001). Glycemia levels reduced significantly (114.5± vs. 107.4± mg/dL, SEM 2.45, p = 0.001). While total cholesterol levels (119.4 vs. 129.6 mg/dL, SEM 2.4, p < 0.001) as well as HDL levels (29.9 vs. 40 mg/dL, SEM 0.62, p < 0.001) significantly increased, triglyceride levels significantly decreased (128.5 vs. 122.1 mg/dL, SEM 3.8, p = 0.048). There was no change in LDL levels. Creatinine levels remained stable throughout the period of rehabilitation. Conclusions: Cardiorespiratory rehabilitation has a significant impact on myocardial function, quality of life in terms of exercise capacity and symptoms (6 MWT) as well as laboratory levels relevant for cardiovascular prevention such as glycemia and lipid profile. Full article

Background: Acute kidney injury (AKI) is one of the common complications of liver cirrhosis. It occurs in nearly 20% of patients with cirrhosis who are hospitalized. Prior literature demonstrated that the AKI occurrence in patients with cirrhosis is independently associated with higher mortality. However, there are data assessing predictors and outcomes of AKI resolution in hospitalized patients with cirrhosis. Therefore, the aim of the current study was to identify clinical predictors of AKI resolution among inpatients with cirrhosis that are easily obtained and to evaluate the clinical outcomes of those patients. Methods: The current study is a retrospective cohort of patients with cirrhosis who were hospitalized and had AKI between 2012 and 2020 at a tertiary referral center. Patients included in this study were identified using the International Classification of Diseases 9 codes and then they were manually verified by two independent chart reviewers. AKI was classified according to the AKI Network (AKIN) serum creatinine (Cr) criteria, with AKIN resolution defined as AKIN stage 1 or lower at the time of discharge, while unresolved AKIN was defined as AKIN stage 2 or 3 at the time of discharge. For univariate analysis, Fisher’s exact and the two-sample T-test were utilized. For multivariable analysis, stepwise logistic regression was performed to evaluate variables associated with AKIN resolution. Survival curves were estimated and compared using the Kaplan–Meier method and Log-Rank Test. A p-value cutoff of 0.05 was used for statistical significance. Results: Between 2012 and 2020, there were 140 patients who were included (59% males). The majority of patients had viral hepatitis (54%) as the cirrhosis etiology with 80% of them having hepatitis C virus. Most patients had fluid-responsive AKI (49%), and stage 1 AKIN (69%). In terms of outcomes, the majority of patients (117 patients; 84%) had AKIN resolution at the time of discharge. In the multivariable analysis, after adjusting for clinical meaningful variables, our study shows that higher albumin value at the time of admission (adjusted Odds Ratio “aOR” = 3.28; p = 0.01) and non-metabolic dysfunction-associated steatotic liver disease (non-MASLD) cirrhosis (aOR = 9.43; p < 0.01) were variables associated with higher odds of AKIN resolution at the time of discharge. Conversely, we show that a higher Cr value at the time of admission was associated with lower odds of AKIN resolution at the time of discharge (aOR = 0.31; p < 0.01). When evaluating mortality, patients with unresolved AKIN at the time of discharge had higher rates of in-hospital mortality (p < 0.01) compared to those with resolved AKIN. Survival curve analyses using the Kaplan–Meier method indicated that patients with resolved AKIN experienced higher 90-day survival rates (p < 0.01). Additionally, those with resolved AKIN demonstrated greater transplant-free survival compared to patients with unresolved AKIN at both the 1-year (p = 0.04) and 3-year (p < 0.01) follow-ups. Conclusions: When evaluating clinical predictors of AKIN resolution in admitted patients with cirrhosis, our study showed that a higher admission albumin value and non-MASLD etiology of cirrhosis were associated with higher odds of AKIN resolution at the time of discharge. Conversely, a higher admission Cr value was associated with lower odds of AKIN resolution at the time of discharge. We also demonstrate that AKIN resolution during index admission was associated with improved short- and long-term transplant-free survival (up to 3 years). Our findings warrant external validation in larger cohorts to further evaluate the impact of inpatient AKI resolution on cirrhosis outcomes. Our findings can help clinicians predict AKIN outcomes and encourage more aggressive management of AKI, especially in high-risk patients, which can improve mortality. Full article

Primary congenital hypothyroidism is easily diagnosed on the basis of elevated plasma levels of thyroid-stimulating hormone (TSH). In contrast, in the rare disorders of thyroid hormone resistance, TSH and, in mild cases, also thyroid hormone levels are within the normal range. Thyroid hormone resistance is caused by defects in hormone metabolism, transport, or receptor activation and can have the same serious consequences for child development as congenital hypothyroidism. A total of n = 23,522 data points from a large cohort of children and young adults were used to generate normal values and sex-specific percentiles for the ratio of free triiodothyronine (T3) to free thyroxine (T4), the fT3/fT4 ratio. The aim was to determine whether individuals with developmental delay and genetically confirmed thyroid hormone resistance, carrying defects in Monocarboxylate Transporter 8 (MCT8), Thyroid Hormone Receptor alpha (THRα), and Selenocysteine Insertion Sequence-Binding Protein 2 (SECISBP2), had abnormal fT3/fT4 ratios. Indeed, we were able to demonstrate a clear separation of patient values for the fT3/fT4 ratio from normal and pathological controls (e.g., children with severe cerebral palsy). We therefore recommend using the fT3/fT4 ratio as a readily available screening parameter in children with developmental delay for the identification of thyroid hormone resistance syndromes. The fT3/fT4 ratio can be easily plotted on centile charts using our free online tool, which accepts various SI and non-SI units for fT3, fT4, and TSH. Full article