Congenital Adrenal Hyperplasia: A Case Report with Premature Teeth Exfoliation and Bone Resorption

Congenital adrenal hyperplasia (CAH) is an inherited autosomal recessive disorder characterized by insufficient production of cortisol. The aim of this case report was to present a child with CAH, premature exfoliation of primary teeth and accelerated eruption of his permanent teeth related to bone resorption. A 4.5-year-old Caucasian boy with CAH and long-term administration of glucocorticoids was referred for dental restoration. Clinical examination revealed primary molars with worn stainless steel crowns, severe attrition of the upper canines, and absence of the upper incisors. Before the completion of treatment, abnormal mobility of the first upper primary molars and the lower incisors was detected, and a few days later the teeth exfoliated prematurely. Histologic examination revealed normal tooth structure. Alkaline phosphatase and blood cells values were normal. Eruption of the permanent dentition was also accelerated. Tooth mobility was noticed in the permanent teeth as soon as they erupted, along with bone destruction. Examination revealed an elevated level of receptor activator of nuclear factor-kB ligand and lower-than-normal osteoprotegerin and vitamin D levels. The patient was treated with vitamin D supplements, and his teeth have been stable ever since. CAH is a serious chronic disorder appearing in children with accelerated dental development and possibly premature loss of primary teeth

Evaluation of sesamum gum as an excipient in matrix tablets

In developing countries modern medicines are often beyond the affordability of the majority of the population. This is due to the reliance on expensive imported raw materials despite the abundance of natural resources which could provide an equivalent or even an improved function. The aim of this study was to investigate the potential of sesamum gum (SG) extracted from the leaves of Sesamum radiatum (readily cultivated in sub-Saharan Africa) as a matrix former. Directly compressed matrix tablets were prepared from the extract and compared with similar matrices of HPMC (K4M) using theophylline as a model water soluble drug. The compaction, swelling, erosion and drug release from the matrices were studied in deionized water, 0.1 N HCl (pH 1.2) and phosphate buffer (pH 6.8) using USP apparatus II. The data from the swelling, erosion and drug release studies were also fitted into the respective mathematical models. Results showed that the matrices underwent a combination of swelling and erosion, with the swelling action being controlled by the rate of hydration in the medium. SG also controlled the release of theophylline similar to the HPMC and therefore may have use as an alternative excipient in regions where Sesamum radiatum can be easily cultivated

Congenital adrenal hyperplasia: A case report with premature teeth exfoliation and bone resorption

Congenital adrenal hyperplasia (CAH) is an inherited autosomal recessive disorder characterized by insufficient production of cortisol. The aim of this case report was to present a child with CAH, premature exfoliation of primary teeth and accelerated eruption of his permanent teeth related to bone resorption. A 4.5-year-old Caucasian boy with CAH and long-term administration of glucocorticoids was referred for dental restoration. Clinical examination revealed primary molars with worn stainless steel crowns, severe attrition of the upper canines, and absence of the upper incisors. Before the completion of treatment, abnormal mobility of the first upper primary molars and the lower incisors was detected, and a few days later the teeth exfoliated prematurely. Histologic examination revealed normal tooth structure. Alkaline phosphatase and blood cells values were normal. Eruption of the permanent dentition was also accelerated. Tooth mobility was noticed in the permanent teeth as soon as they erupted, along with bone destruction. Examination revealed an elevated level of receptor activator of nuclear factor-κB ligand and lower-than-normal osteoprotegerin and vitamin D levels. The patient was treated with vitamin D supplements, and his teeth have been stable ever since. CAH is a serious chronic disorder appearing in children with accelerated dental development and possibly premature loss of primary teeth. Copyright © 2015 by the American Academy of Pediatrics

Three-dimensional evaluation of mandibular bone regenerated by bone transport distraction osteogenesis

The purpose of this study was to evaluate the structure and material properties of native mandibular bone and those of early regenerate bone, produced by bone transport distraction osteogenesis. Ten adult foxhounds were divided into two groups of five animals each. In all animals, a 3- to 4-cm defect was created on one side of the mandible. A bone transport reconstruction plate, consisting of a reconstruction plate with an attached intraoral transport unit, was utilized to stabilize the mandible and regenerate bone at a rate of 1 mm/day. After the distraction period was finished, the animals were killed at 6 and 12 weeks of consolidation. Micro-computed tomography was used to assess the morphometric and structural indices of regenerate bone and matching bone from the unoperated contralateral side. Significant new bone was formed within the defect in the 6- and 12-week groups. Significant differences (P = 0.05) between mandibular regenerated and native bone were found in regard to bone volume fraction, mineral density, bone surface ratio, trabecular thickness, trabecular separation, and connectivity density, which increased from 12 to 18 weeks of consolidation. We showed that regenerated bone is still mineralizing and that native bone appears denser because of a thick outer layer of cortical bone that is not yet formed in the regenerate. However, the regenerate showed a significantly higher number of thicker trabeculae. © 2011 Springer Science+Business Media, LLC

Biomechanical characteristics of regenerated cortical bone in the canine mandible

To test the mechanical properties of regenerate cortical bone created using mandibular bone transport (MBT) distraction, five adult male American foxhound dogs underwent unilateral distraction of the mandible with a novel MBT device placed to linearly repair a 30-35 mm bone defect. The animals were sacrificed 12 weeks after the beginning of the consolidation period. Fourteen cylindrical specimens were taken from the inner (lingual) and outer (buccal) plates of the reconstructed mandible and 21 control specimens were removed from the contralateral aspect of the mandible. The mechanical properties of the 35 cylindrical cortical bone specimens were assessed by using a non-destructive pulse ultrasound technique. Results showed that all of the cortical mechanical properties exhibit higher numerical values on the control side than the MBT regenerate side. In addition, both densities and the elastic moduli in the direction of maximum stiffness of the regenerate cortical bone specimens are higher on the lingual side than the buccal side. Interestingly, there is no statistical difference between elastic modulus (E1 and E2) in orthogonal directions throughout the 35 cortical specimens. The data suggest that not only is the regenerate canine cortical bone heterogeneous, but the elastic mechanical properties tend to approximate transverse isotropy at a tissue level, as opposed to control cortical bone, which is orthotropic. In addition, the elastic mechanical properties are higher not only on the control side but also in the lingual anatomical position, suggesting a stress shielding effect from the presence of the reconstruction plate. © 2011 John Wiley & Sons, Ltd

An observational study to assess the molecular epidemiology and direct medical costs of epidermal growth factor receptor (Egfr) mutations in patients with advanced egfr mutation-positive non-small cell lung cancer treated with afatinib in real-world clinical settings in Greece

Purpose: Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are the preferred first-line option for patients with advanced, EGFR-mutant non-small cell lung cancer (NSCLC). Afatinib, a second-generation irreversible EGFR-TKI, has been exten-sively used in Greece in this setting; however, real-world data regarding molecular epidemiology and financial implications of afatinib use are lacking. Materials and Methods: This was an observational, non-interventional, multicenter, retro-spective cohort study, based on real-world data collected from the medical charts/records of patients treated with afatinib between 15/03/2015 and 25/06/2020 and were recorded on a web-based data capture system. Cox models were used to assess the prognostic significance of clinicopathological parameters with respect to clinical outcomes of interest. Cost analysis was conducted from a public third-payer perspective, and only direct medical costs reim-bursed by the payer were considered. Results: A total of 59 patients were treated with afatinib for their EGFR mutation-positive advanced NSCLC; the median age was 61 years (range: 37–91). Performance status was zero in 61%, and brain metastases were present in 13.6%. Forty-four patients (74.6%) had a deletion in exon 19 only, while nine (15.3%) had a mutation in exon 21, 8 of them in L858R and one in L861Q. At a median follow-up of 41.8 months (95% CI 35.9–51.4), the median PFS was 14.3 months (95% CI 12.2–16.4), and the median OS was 29 months (95% CI 25.6–33.4). Corresponding values for patients with deletion 19 only were 14.3 months (95% CI 11.5–18.5) and 28.1 months (95% CI 21.1–32.6), respectively. The mean expendi-ture for the treatment of each patient equals €25,333.68; with €21,865.06 being attributed to drug acquisition costs, €3325.35 to monitoring costs and €143.27 to adverse event treatment-related costs. Conclusion: Long-term data in the real-world setting in Greece confirm activity, tolerability and cost-effectiveness of afatinib as first-line treatment of patients with advanced EGFR-mutant NSCLC. Clinical Trial Registration: Clinicaltrials.gov NCT04640870. © 2021 Mountzios et al

Effect of Aging and Ice Structuring Proteins on the Morphology of Frozen Hydrated Gluten Networks

The present investigation constitutes an attempt to rationalize the effect of aging and ice structuring proteins (ISPs) on the network morphology of frozen hydrated gluten. In doing so, it employs differential scanning calorimetry, time-domain NMR, dynamic oscillation on shear, creep testing, and electron microscopy. Experimentation and first principles modeling allows identification and description of the processes of ice formation and recrystallization in molecular terms. It is demonstrated that in the absence of a readily discernible glass transition temperature in gluten−ice composites, the approach of considering the melting point and aging at constant or fluctuating temperature conditions in the vicinity of this point can provide a valid index of functional quality. A theoretical framework supporting the concept of capillary confined frozen water in the gluten matrix was advanced, and it was found that ISPs were effective in controlling recrystallization both within these confines and within ice in the bulk

Real-world clinical outcome and toxicity data and economic aspects in patients with advanced breast cancer treated with cyclin-dependent kinase 4/6 (CDK4/6) inhibitors combined with endocrine therapy: The experience of the Hellenic Cooperative Oncology Group

Background We evaluated real-world clinical outcomes and toxicity data and assessed treatment-related costs in patients with advanced breast cancer who received treatment with cyclin-dependent kinase inhibitors (CDKi). Patients and methods We conducted a prospective-retrospective analysis of patients with advanced hormone receptor-positive, human epidermal growth factor receptor 2-negative breast cancer who received a CDKi, in combination with endocrine therapy, at any line of treatment. The primary endpoint was progression-free survival (PFS). Cost analysis was conducted from a public third-payer (National Organization for Healthcare Services Provision (EOPYY)) perspective, assessing only costs related to direct medical care, including drug therapy costs and adverse drug reaction (ADR)-related costs. Results From July 2015 to October 2019, 365 women received endocrine therapy combined with CDKi; median age was 61 years, postmenopausal 290 (80.6%) patients. CDKi were administered as first-line treatment in 149 (40.9%) patients, second-line treatment in 96 (26.4%) and third-line treatment and beyond in 119 (32.7%) patients. The most common adverse events were neutropenia, anaemia, thrombocytopenia and fatigue. Grade 3-4 adverse events occurred in 86 (23.6%) patients, whereas 8 (2.2%) patients permanently discontinued treatment due to toxicity. The median PFS for patients who received CDKi as first-line, second-line and third-line treatment and beyond was 18.7, 12 and 7.4 months, respectively. The median overall survival since the initiation of CDKi treatment was 29.9 months (95% CI: 23.0-not yet reached (NR)). The mean pharmaceutical therapy cost estimated per cycle was 2 724.12 € for each patient, whereas the main driver of the ADR-related costs was haematological adverse events. Conclusions Treatment with CDKi was well tolerated, with a low drug discontinuation rate. Patients who received CDKi as first-line treatment had improved PFS and OS compared with second-line treatment and beyond. The main component of direct medical costs assessed in the cost analysis comprises CDKi pharmaceutical therapy costs. Trial registration number NCT04133207. © Author (s) (or their employer(s)) 2020. Re-use permitted under CC BY. Published by BMJ on behalf of the European Society for Medical Oncology