Prevalence of radix accesoria dentis in a northern Peruvian population evaluated by cone-beam tomography.

Radix accessoria dentis are anatomical variations of the mandibular molars and identifying them radiographically can be challenging for the clinician, especially in specific areas such as endodontics. The objective this study was to determine the prevalence of radix accessoria dentis evaluated in cone-beam computed tomography in a northern Peruvian population. The study design was descriptive and cross-sectional. The sample consisted of 2640 permanent mandibular first and second molar teeth evaluated by cone beam tomography. Non-probabilistic convenience sampling was used. For the analysis of radix accesoria dentis, the axial and coronal views of the tomography were evaluated. Prevalence was evaluated according to sex and according to type of tooth and average length. The statistical analyses used were the chi-square test and Kruskal-Wallis H test to find the correlation of the variables. A prevalence of 2.5 % of radix accesoria dentis was determined. According to sex, radix accesoria dentis was present in 1.36 % in females and 1.14 % in males (p > 0.05). The tooth 4.6 obtained the highest prevalence with 1.33 % (p > 0.05) and the average length of radix accesoria dentis found was 9.27 mm (p > 0.05). The prevalence of the radix accesoria dentis evaluated in cone beam tomography in a northern Peruvian population is low. Sex does not influence its presentation. Mandibular first molars are the ones that present the greatest amount of this anatomical variation and the average length of the radix accesoria dentis is less than 10 mm.

Gender-affirming hormonal therapy induces a gender-concordant fecal metagenome transition in transgender individuals.

BACKGROUND: Limited data exists regarding gender-specific microbial alterations during gender-affirming hormonal therapy (GAHT) in transgender individuals. This study aimed to investigate the nuanced impact of sex steroids on gut microbiota taxonomy and function, addressing this gap. We prospectively analyzed gut metagenome changes associated with 12 weeks of GAHT in trans women and trans men, examining both taxonomic and functional shifts. METHODS: Thirty-six transgender individuals (17 trans women, 19 trans men) provided pre- and post-GAHT stool samples. Shotgun metagenomic sequencing was used to assess the changes in gut microbiota structure and potential function following GAHT. RESULTS: While alpha and beta diversity remained unchanged during transition, specific species, including Parabacteroides goldsteinii and Escherichia coli, exhibited significant abundance shifts aligned with affirmed gender. Overall functional metagenome analysis showed a statistically significant effect of gender and transition (R2 = 4.1%, P = 0.0115), emphasizing transitions aligned with affirmed gender, particularly in fatty acid-related metabolism. CONCLUSIONS: This study provides compelling evidence of distinct taxonomic and functional profiles in the gut microbiota between trans men and women. GAHT induces androgenization in trans men and feminization in trans women, potentially impacting physiological and health-related outcomes. TRIAL REGISTRATION: Clinicaltrials.gov NCT02185274.

Patient autonomy and shared decision-making in the context of clinical trial participation.

AIMS: This study aimed to explore how incorporating shared decision-making (SDM) can address recruitment challenges in clinical trials. Specifically, it examines how SDM can align the trial process with patient preferences, enhance patient autonomy and increase active patient participation. Additionally, it identifies potential conflicts between SDM and certain clinical trial aspects, such as randomization or blinding, and proposes solutions to mitigate these issues. MATERIALS AND METHODS: We conducted a comprehensive review of existing literature on patient recruitment challenges in clinical trials and the role of SDM in addressing these challenges. We analysed case studies and trial reports to identify common obstacles and assess the effectiveness of SDM in improving patient accrual. Additionally, we evaluated three proposed solutions: adequate trial design, communication skill training and patient decision aids. RESULTS: Our review indicates that incorporating SDM can significantly enhance patient recruitment by promoting patient autonomy and engagement. SDM encourages physicians to adopt a more open and informative approach, which aligns the trial process with patient preferences and reduces psychological barriers such as fear and mental stress. However, implementing SDM can conflict with elements such as randomization and blinding, potentially complicating trial design and execution. DISCUSSION: The desire for patient autonomy and active engagement through SDM may clash with traditional clinical trial methodologies. To address these conflicts, we propose three solutions: redesigning trials to better accommodate SDM principles, providing communication skill training for physicians and developing patient decision aids. By focussing on patient wishes and emotions, these solutions can integrate SDM into clinical trials effectively. CONCLUSION: Shared decision-making provides a framework that can promote patient recruitment and trial participation by enhancing patient autonomy and engagement. With proper implementation of trial design modifications, communication skill training and patient decision aids, SDM can support rather than hinder clinical trial execution, ultimately contributing to the advancement of evidence-based medicine.

Gynecomastia and Its Management In Boys With Partial Androgen Insensitivity Syndrome.

INTRODUCTION: Partial androgen insensitivity syndrome (PAIS) is a rare condition that is reported to be commonly associated with gynecomastia in males. OBJECTIVES: To assess the management of gynecomastia in male PAIS. MATERIALS AND METHODS: Retrospective review of males with PAIS over the age of 10 years in the I-DSD registry. RESULTS: Of the 205 eligible cases, information was available for 57 from 13 centers. An androgen receptor gene variant was confirmed in 45 (79%) with a median age at first presentation of 1.0 year (range 0.1, 26.0). Of the 45 genetically confirmed cases, gynecomastia was present in 41 (91%) with a median age at the time of gynecomastia development of 13.5 years (11.0, 29.0). In the other 4 (9%) with no gynecomastia, the median age at last assessment was 15.7 years (10.6, 17.0). In 30 cases with information available, micropenis was present at the time of gynecomastia development in 23 (77%). Of the 35 with information available, 2 (6%) exhibited spontaneous resolution between the ages of 15 and 21 years and 25 (71%) had breast surgery at a median age of 15.7 years (14.0, 23.0). Of these 25, 9 (26%) had previously received medical therapy. The median clinician score of effectiveness for medical therapy was 3 (1, 8) compared to 10 (3, 10) for surgery (P < .0001). In 31 with information available, 13 (42%) had received psychology support. CONCLUSION: Gynecomastia is common in PAIS but not universal. Surgical management may be more effective than medical therapy, but there is a need for further standardized and systematic studies.

Stage I and II nonsmall cell lung cancer treatment options.

Chest radiography, computed tomography (CT) and positron emission tomography (PET)-CT are required for staging nonsmall cell lung cancers. Stage I cancers may be up to 4 cm in maximal diameter, with stage IA tumours being up to 3 cm and stage IB up to 4 cm. A lung cancer becomes stage II if the tumour is between 4 and ≤5 cm (stage IIA), or it spreads to ipsilateral peribronchial or hilar lymph nodes (stage IIB). Stage IA tumours should be surgically resected, ideally using minimally invasive methods. Lobectomy is usually performed, although some studies have shown good outcomes for sublobar resections. If surgery is not possible, stereotactic body radiotherapy is a good alternative. This involves delivering a few high-dose radiation treatments at very high precision. For stage IB to IIB disease, combinations of surgery, chemotherapy or immunotherapy and radiotherapy are used. There is evidence that neoadjuvant treatment (immunotherapy with nivolumab and chemotherapy for stage IB and II) optimises outcomes. Adjuvant chemotherapy with a platinum-based doublet (typically cisplatin+vinorelbine) should be offered for resected stage IIB tumours and considered for resected IIA tumours. Adjuvant pembrolizumab is used for stage IB-IIIA following resection and adjuvant platinum-based chemotherapy. Osimertinib may be used for resected stage IB to IIIA cancers which have relevant mutations (epidermal growth factor receptor exon 19 deletions or exon 21 (L858R) substitution). There are no fixed guidelines for follow-up, but most centres recommend 6-monthly CT scanning for the first 2-3 years after definitive treatment, followed by annual scans.

Are Hospital Admissions (Costs) and Mortality Rate Impacted by Guideline-driven Treatment of Heart Failure?: A Comparison between Participants in the "CorBene" CMP and Standard-care Patients on the Basis of Propensity Score Matching.

Heart failure (HF) is one of the most common diagnoses on admission to hospital in Germany, and one which incurs high costs. Integrated care in case management programs (CMPs) aims to improve treatment quality in the sense of guideline-driven treatment, while reducing hospital admissions, hospital costs, and mortality. A total of 1,844 patient data records from 11 German statutory health insurance companies enrolled in the CMP (intervention group [IG]) were compared with 1,844 standard-care patients (control group) using propensity score matching. The two groups were assessed over three follow-up observation periods regarding the endpoints' treatment costs, hospitalization rate, indicators for treatment quality (diagnostics, physician contact), and mortality. The evaluation revealed no significant differences regarding overall costs. The IG incurred significantly higher outpatient costs, but the medication costs and inpatient costs were not significantly different. There were also no significant differences in the number of hospital admissions. Patients within the CMP had significantly more frequent contact with a cardiologist, and underwent echocardiographic examination significantly more frequently. Mortality during the first follow-up observation year was considerably more favorable for the IG. There are indications that treatment quality is improved in HF patients.

Safety and performance of the new med-el total ossicular replacement prostheses.

PURPOSE: This multicentric, retrospective study provides safety and performance data of the MED-EL total ossicular replacement prostheses (TORP). METHODS: Patients underwent tympanoplasty with mXACT Total Prosthesis Center, mXACT Total Prosthesis Offcenter or mXACT PRO Total Prosthesis. The clinical data were retrospectively analyzed. Follow-up examination included access to the medical record (for adverse events) of the patients, ear microscopy and pure-tone audiometry to determine the post-operative pure tone average of the frequencies 0.5, 1, 2 and 3 kHz (PTA4). The post-operative PTA4 air bone gap (ABG) was used to evaluate the audiological outcome. A post-operative minimum and maximum follow-up period was not defined. RESULTS: 103 patients were implanted with a TORP. 102 (88 adults, 14 children; 37 CHL, 64 MHL, 1 not specified) patients were analyzed for safety and 92 (79 adults, 13 children) patients for performance of the prostheses. ADVERSE EVENTS RESULTS (N = 102): In 1 patient (child, mXACT Total Prosthesis Offcenter) a prosthesis dislocation was reported, which lead to a revision surgery. No prosthesis extrusion or migration was reported. AUDIOLOGICAL RESULTS (N = 92): 49 (53.3%) of the 92 patients had a PTA4 ABG of ≤ 20 dB and therefore a successful rehabilitation. The mean post-operative PTA4 ABG of all 92 patients was 21.0 ± 9.7 dB. The first endpoint, improvement in post-operative PTA4 ABG of ≤ 20 dB by ≥ 25% of the patients was achieved. The individual Δ BC PTA4 (post-operative minus pre-operative BC PTA4) thresholds were stable (within ± 5 dB HL) in 91 (98.9%) patients. 1 patient had a BC PTA4 deterioration of 11.3 dB HL. CONCLUSION: The MED-EL TORPs are safe and effective for middle ear reconstruction. Trial registration number NCT05565339, September 09, 2022, retrospectively registered.

Global Adrenal Insufficiency in Two Independent Patients Carrying the Same Homozygous c.172A>G, p.(Thr58Ala) Mutation in the TBX19 Gene.

INTRODUCTION: TBX19 mutations cause isolated ACTH-deficiency. While this classically results in severe hypocortisolism, potential consequences for mineralocorticoid biosynthesis have not been described to date. Liquid chromatography mass spectrometry (LC-MS/MS) and gas chromatography mass spectrometry (GC-MS) allow novel insights into the steroid metabolism of pediatric endocrine diseases. CASE PRESENTATION: Patient 1 (female) presented right after birth with hypoglycemia and hyponatremia (minimum sodium 126 mmol/L). She recovered under therapy with hydrocortisone, fludrocortisone and initial NaCl. Patient 2 (male) presented after birth with prolonged cholestatic jaundice. Only at the age of 3.5 months, repeated episodes of hypoglycemia occurred. Both patients showed severely reduced ACTH. LC-MS/MS analyses on plasma samples demonstrated combined reduced glucocorticoid- and mineralocorticoid biosynthesis confirmed by GC-MS analyses on spot urine. In contrast to patient 1, patient 2 (currently 8 years old) never suffered from hyponatremia. Both patients carry the same homozygous c.172A>G, p.(Thr58Ala) mutation in the TBX19 gene proving isolated ACTH-deficiency. CONCLUSION: Isolated ACTH-deficiency can be associated with reduced mineralocorticoids and hyponatremia. We hypothesize that sufficient pituitary ACTH secretion is an important predisposition for regular adrenal mineralocorticoid biosynthesis.

Medium-term outcomes after magnetic sphincter augmentation vs. fundoplication for reflux disease due to hiatal hernia: a propensity-score matched comparison in 282 patients.

BACKGROUND: An increasing number of reflux patients opt for magnetic sphincter augmentation (MSA) instead of fundoplication. However, few studies compare the medium-term efficacy and safety of the procedures. METHODS: We conducted a retrospective single-center analysis of consecutive MSA and Nissen fundoplication cases between 01/2015 and 06/2020. Patients underwent surgery, including hiatoplasty, for medical treatment-resistant reflux due to hiatal hernia. Surgical revision and proton pump inhibitor (PPI) reuptake rates were the primary outcomes. We also compared adverse event rates. Patients with severe preoperative dysphagia/motility disorders were assigned different treatment pathways and excluded from the analysis. We used propensity-score matching to reduce confounding between treatments. RESULTS: Out of 411 eligible patients, 141 patients who underwent MSA and 141 with fundoplication had similar propensity scores and were analyzed. On average, patients were 55 ± 12 years old and overweight (BMI: 28 ± 5). At 3.9 years of mean follow-up, MSA was associated with lower surgical revision risk as compared to fundoplication (1.2% vs 3.0% per year, respectively; HR: 0.38; 95% CI 0.15-0.96; p = 0.04), and similar PPI-reuptake risk (2.6% vs 4.2% per year; HR: 0.59; 95% CI 0.30-1.16; p = 0.12). Adverse event rates during primary stay were similar (MSA vs. fundoplication: 1% vs. 3%, p = 0.68). Fewer patients experienced adverse events in the MSA group after discharge (24% vs. 33%, p = 0.11), driven by higher rates of self-limiting dysphagia (1% vs. 9%, p < 0.01) and gas/bloating (10% vs. 18%, p = 0.06) after fundoplication. Differences between MSA and fundoplication in dysphagia requiring diagnostic endoscopy (11% vs. 8%, p = 0.54) or surgical revision (2% vs. 1%, p = 1.0) were non-significant. The device explantation rate was 4% (5/141). CONCLUSION: MSA reduces the re-operation risk compared to fundoplication and may decrease adverse event rates after discharge. Randomized head-to-head studies between available surgical options are needed.

LINE1-mediated epigenetic repression of androgen receptor transcription causes androgen insensitivity syndrome.

Androgen insensitivity syndrome (AIS) is a difference of sex development (DSD) characterized by different degrees of undervirilization in individuals with a 46,XY karyotype despite normal to high gonadal testosterone production. Classically, AIS is explained by hemizygous mutations in the X-chromosomal androgen receptor (AR) gene. Nevertheless, the majority of individuals with clinically diagnosed AIS do not carry an AR gene mutation. Here, we present a patient with a 46,XY karyotype, born with undervirilized genitalia, age-appropriate testosterone levels and no uterus, characteristic for AIS. Diagnostic whole exome sequencing (WES) showed a maternally inherited LINE1 (L1) retrotransposon insertion in the 5' untranslated region (5'UTR) of the AR gene. Long-read nanopore sequencing confirmed this as an insertion of a truncated L1 element of ≈ 2.7 kb and showed an increased DNA methylation at the L1 insertion site in patient-derived genital skin fibroblasts (GSFs) compared to healthy controls. The insertion coincided with reduced AR transcript and protein levels in patient-derived GSFs confirming the clinical diagnosis AIS. Our results underline the relevance of retrotransposons in human disease, and expand the growing list of human diseases associated with them.

Virtual reality simulation to enhance advanced trauma life support trainings - a randomized controlled trial.

BACKGROUND: Advanced Trauma Life Support (ATLS) is the gold standard of initial assessment of trauma patients and therefore a widely used training program for medical professionals. Practical application of the knowledge taught can be challenging for medical students and inexperienced clinicians. Simulation-based training, including virtual reality (VR), has proven to be a valuable adjunct to real-world experiences in trauma education. Previous studies have demonstrated the effectiveness of VR simulations for surgical and technical skills training. However, there is limited evidence on VR simulation training specifically for trauma education, particularly within the ATLS curriculum. The purpose of this pilot study is to evaluate the feasibility, effectiveness, and acceptance of using a fully immersive VR trauma simulation to prepare medical students for the ATLS course. METHODS: This was a prospective randomised controlled pilot study on a convenience sample of advanced medical students (n = 56; intervention group with adjunct training using a commercially available semi-automated trauma VR simulation, n = 28, vs control group, n = 28) taking part in the ATLS course of the Military Physician Officer School. Feasibility was assessed by evaluating factors related to technical factors of the VR training (e.g. rate of interruptions and premature termination). Objective and subjective effectiveness was assessed using confidence ratings at four pre-specified points in the curriculum, validated surveys, clinical scenario scores, multiple choice knowledge tests, and ATLS final clinical scenario and course pass rates. Acceptance was measured using validated instruments to assess variables of media use (Technology acceptance, usability, presence and immersion, workload, and user satisfaction). RESULTS: The feasibility assessment demonstrated that only one premature termination occurred and that all remaining participants in the intervention group correctly stabilised the patient. No significant differences between the two groups in terms of objective effectiveness were observed (p = 0.832 and p = 0.237 for the pretest and final knowledge test, respectively; p = 0.485 for the pass rates for the final clinical scenario on the first attempt; all participants passed the ATLS course). In terms of subjective effectiveness, the authors found significantly improved confidence post-VR intervention (p < .001) in providing emergency care using the ATLS principles. Perceived usefulness in the TEI was stated with a mean of 4 (SD 0.8; range 0-5). Overall acceptance and usability of the VR simulation was rated as positive (System Usability Scale total score mean 79.4 (SD 11.3, range 0-100). CONCLUSIONS: The findings of this prospective pilot study indicate the potential of using VR trauma simulations as a feasible and acceptable supplementary tool for the ATLS training course. Where objective effectiveness regarding test and scenario scores remained unchanged, subjective effectiveness demonstrated improvement. Future research should focus on identifying specific scenarios and domains where VR can outperform or enhance traditional learning methods in trauma simulation.

Title and abstract screening for literature reviews using large language models: an exploratory study in the biomedical domain.

BACKGROUND: Systematically screening published literature to determine the relevant publications to synthesize in a review is a time-consuming and difficult task. Large language models (LLMs) are an emerging technology with promising capabilities for the automation of language-related tasks that may be useful for such a purpose. METHODS: LLMs were used as part of an automated system to evaluate the relevance of publications to a certain topic based on defined criteria and based on the title and abstract of each publication. A Python script was created to generate structured prompts consisting of text strings for instruction, title, abstract, and relevant criteria to be provided to an LLM. The relevance of a publication was evaluated by the LLM on a Likert scale (low relevance to high relevance). By specifying a threshold, different classifiers for inclusion/exclusion of publications could then be defined. The approach was used with four different openly available LLMs on ten published data sets of biomedical literature reviews and on a newly human-created data set for a hypothetical new systematic literature review. RESULTS: The performance of the classifiers varied depending on the LLM being used and on the data set analyzed. Regarding sensitivity/specificity, the classifiers yielded 94.48%/31.78% for the FlanT5 model, 97.58%/19.12% for the OpenHermes-NeuralChat model, 81.93%/75.19% for the Mixtral model and 97.58%/38.34% for the Platypus 2 model on the ten published data sets. The same classifiers yielded 100% sensitivity at a specificity of 12.58%, 4.54%, 62.47%, and 24.74% on the newly created data set. Changing the standard settings of the approach (minor adaption of instruction prompt and/or changing the range of the Likert scale from 1-5 to 1-10) had a considerable impact on the performance. CONCLUSIONS: LLMs can be used to evaluate the relevance of scientific publications to a certain review topic and classifiers based on such an approach show some promising results. To date, little is known about how well such systems would perform if used prospectively when conducting systematic literature reviews and what further implications this might have. However, it is likely that in the future researchers will increasingly use LLMs for evaluating and classifying scientific publications.

Behavior and circadian glucocorticoids in prepubertal monozygotic twins with birthweight differences: A prospective longitudinal cohort study on twin-to-twin transfusion syndrome patients.

BACKGROUND/OBJECTIVE: Low birthweight may have adverse sequelae in later life. Therefore, we analyzed behavioral difficulties and salivary glucocorticoid profiles in monozygotic twins with intra-twin birthweight differences due to twin-to-twin transfusion syndrome (TTTS). METHODS: 46 monozygotic TTTS twin pairs with birthweight differences of <1SDS (concordant; n=29) and ≥1SDS (discordant; n=17) were recruited at a mean age of 6.9 years for a prospective longitudinal cohort study. For glucocorticoid analysis, saliva samples were collected (at 7 h, 13 h, 18 h and 21 h) and analyzed with liquid chromatography-tandem mass spectrometry. Parents completed the Strengths and Difficulties Questionnaire. RESULTS: From the parents' perspective, the formerly smaller twins had statistically higher scores regarding hyperactivity (mean 4.63 vs 3.48, p=0.003) and emotional problems (mean 2.67 vs 2.02, p=0.042). Less catch-up growth (Δintra-twin height SDS 4 years of age - Δintra-twin birth length SDS) of the smaller twins was associated with higher scores for hyperactivity (Adj. R²=0.261, p<0.001, ß=-1.88, F(1.44)=16.86, n=46, f²=0.35), while smaller birthweight (Adj. R²=0.135, p=0.007, ß=-0,87, F(1.44)=8.03, n=46, f²=0.16) and birth length (Adj. R²=0.085, p=0.028, ß=-0,78, F(1.44)=5.19, n=46, f²=0.09) were associated with higher scores for peer problems. Greater Δintra-twin for cortisol (7 h: rho=0.337, p=0.029; cumulative: rho=0.458; p=0.024) and cortisone (7 h: rho=0.329, p=0.029; 13 h: rho=0.436, p=0.005) correlated with a greater Δintra-twin for conduct problems. In the discordant group, circa 1 SDS in head circumference persisted from birth (mean SDS: smaller twin -1.18, larger twin -0.08, p<0.001) to present (mean SDS: smaller twin -1.16, larger twin -0.14, p<0.001). CONCLUSION: Higher cortisol and cortisone concentrations in smaller twins were associated with higher scores for conduct problems. Lower birthweight and absent catch-up growth affected the parents' perspective on the smaller twins' behavior. They saw those children as more hyperactive, with more peer problems and emotional problems. Thus, it seems important to introduce regular check-ups where behavioral difficulties can be assessed, and assistance and advice can be given to the families. Due to the persisting smaller head circumference in the smaller discordant twins, this should be measured regularly.

The value of AI-based analysis of fractional flow reserve of volume computed tomographically detected coronary artery stenosis with regard to their hemodynamic relevance. / Die Bedeutung KI-basierter Analyse fraktioneller Flussreserven computertomografisch nachgewiesener Coronararterienstenosen im Hinblick auf deren hämodynamische Relevanz.

The aim of our work was to demonstrate the importance of artificial intelligence-based analysis of fractional flow reserves of computed tomographically detected coronary artery stenosis with regard to their hemodynamic relevance in patients with unclear chest pain and suspected stable coronary heart disease with a low to medium pre-test probability.The collective of our retrospective analysis includes 63 patients in whom coronary artery stenosis was detected by volume computed tomographic examination in "one beat, whole heart" mode in the period from March to October 2022. In these patients, the fractional flow reserve was also determined by computed tomography, which was modulated by the use of artificial intelligence.The calculated values of the fractional flow reserve and the degrees of stenosis determined by computed tomography showed a moderate and significant negative correlation for all three coronary vascular territories (LAD/CX/RCA) (correlation coefficient rho = 0.54/0.54/0.6; p < 0.01 respectively). In just over a third (37.6 %) of all stenoses classified as high-grade by computed tomography, the assessment of hemodynamic relevance by calculating the fractional flow reserve deviated from the severity of the stenosis diagnosed by computed tomography, while the results in the peripheral areas "no stenosis/vascular occlusion" were 100 % consistent in each case.The present results of this work illustrate that the calculation of the fractional flow reserve based on artificial intelligence as a supplement to volume computed tomography of the heart can make a decisive contribution to further therapy planning by increasing the specificity of the purely morphological method by the physiological aspect. · Calculation of fractional flow reserve is a useful addition to computed tomography of the heart.. · It provides possibility to dispense with unnecessary further diagnostics by increasing specificity.. · The combination of both procedures leads to therapy optimization for patients.. · Noblé H, Mühlbauer N, Ehling J et al. The value of AI-based analysis of fractional flow reserve of volume computed tomographically detected coronary artery stenosis with regard to their hemodynamic relevance. Fortschr Röntgenstr 2024; DOI: 10.1055/a-2271-0887.

New liquid chromatography tandem mass spectrometry reference data for estradiol show mini-puberty in both sexes and typical pre-pubertal and pubertal patterns.

CONTEXT: Reliable estradiol (E2) reference intervals (RIs) are crucial in pediatric endocrinology. OBJECTIVES: This study aims to develop a sensitive ultra-performance liquid chromatographic tandem mass spectrometry (UPLC-MS/MS) method for E2 in serum, to establish graphically represented RI percentiles and annual RIs for both sexes, and to perform a systematic literature comparison. METHODS: First, a UPLC-MS/MS method for E2 was developed. Second, graphically represented RI percentiles and annual RIs covering 0-18 years were computed (cohort of healthy children [1181 girls and 543 boys]). Subsequently, RIs were compared with published data by systematic searches. RESULTS: Lower limit of quantification was 11 pmol/L, indicating high sensitivity. Estradiol first peaked during mini-puberty in both sexes (girls up to 192 pmol/L; boys up to 225 pmol/L). As could be expected, girls showed higher pubertal E2 (up to 638 pmol/L). However, boys' RIs (up to 259 pmol/L) overlapped considerably. We found 4 studies in the literature that also used LC-MS/MS to determine E2 and published RIs for the complete pediatric age range. Reference intervals varied considerably. Pre-pubertal and pubertal phases were present in all studies. Higher E2 during the time of mini-puberty in both sexes was documented in 3 studies including ours. CONCLUSIONS: Variability of RIs for E2 between studies illustrates the importance of laboratory-specific RIs despite using a LC-MS/MS reference method. In boys, the striking E2 peak during mini-puberty as well as high pubertal E2 without phenotypic estrogenization in regular male puberty indicates that the role of E2 in children and, especially in boys, requires better functional understanding.

Treatment Response Biomarkers: Working Toward Personalized Radiotherapy for Lung Cancer.

Owing to major advances in the field of radiation oncology, patients with lung cancer can now receive technically individualized radiotherapy treatments. Nevertheless, in the era of precision oncology, radiotherapy-based treatment selection needs to be improved as many patients do not benefit or are not offered optimum therapies. Cost-effective robust biomarkers can address this knowledge gap and lead to individuals being offered more bespoke treatments leading to improved outcome. This narrative review discusses some of the current achievements and challenges in the realization of personalized radiotherapy delivery in patients with lung cancer.