Nasal route of administration offers a unique opportunity of brain targeted drug delivery via olfactory and trigeminal pathway, providing effective CNS concentrations at lower doses and lower risk for adverse reactions compared to systemic drug administration. Therefore, it has been recently proposed as a route of choice for glucocorticoids to control neuroinflammation processes in patients with severe Covid-19. However, appropriate delivery systems tailored to enhance their efficacy yet need to emerge. In this work we present the development of sprayable brain targeting powder delivery platform of dexamethasone sodium phosphate (DSP). DSP-loaded microspheres, optimised employing Quality-by-Design approach, were blended with soluble inert carriers (mannitol or lactose monohydrate). Powder blends were characterized in terms of homogeneity, flow properties, sprayability, in vitro biocompatibility, permeability and mucoadhesion. Nasal deposition studies were performed using 3D printed nasal cavity model. Mannitol provided better powder blend flow properties compared to lactose. Microspheres blended with mannitol retained or enlarged their mucoadhesive properties and enhanced DSP permeability across epithelial model barrier. DSP dose fraction deposited in the olfactory region reached 17.0% revealing the potential of developed powder platform for targeted olfactory delivery. The observed impact of nasal cavity asymmetry highlighted the importance of individual approach when aiming olfactory region.

Intrathyroidal parathyroid carcinoma is extremely rare clinical entity with potentially multiple diagnostic pitfalls. We report a case of 40-year-old man presented with classical manifestations of primary hyperparathyroidism, severe hypercalcemia and profoundly increased serum parathyroid hormone level. Neck ultrasonography demonstrated multinodular goiter with predominant 34 mm nodule in left thyroid lobe. Additional 16 mm nodule was found beneath the left lobe. Routine percutaneous fine-needle aspiration of predominant nodule indicated follicular thyroid carcinoma, while left inferior nodule was confirmed to be of parathyroid origin. The patient underwent surgery, during which frozen sections identified medullary thyroid carcinoma with metastasis to upper mediastinal lymph node. Permanent sections of the predominant left lobe nodule revealed intrathyroidal parathyroid carcinoma surrounded with multiple microscopic metastases. Left inferior nodule was metastatic lymph node. Additional 10 mm intrathyroidal metastasis of primary parathyroid carcinoma was found within right thyroid lobe. This case indicates that fine-needle-aspiration and intraoperative biopsy are of limited value in diagnosing parathyroid carcinoma, especially if localized intrathyroidally. Oncological en-block resection is treatment of choice, implying ipsilateral lobectomy in case of thyroid invasion. This firstly described case of intrathyroidal parathyroid carcinoma causing intrathyroidal dissemination may influence future treatment strategies.

The concept of diagnostics and therapy of musculoskeletal and neuropathic diseases of the stomatognathic system, which are the subject of this paper, has been developing for decades. It can be said that in order to avoid misunderstanding, the orofacial pain as a clinical problem, in the narrower sense, involves non-odontogenic and non-malignant causes of orofacial region. In this study, the results of clinical diagnosis of the population of 557 consecutive patients with orofacial pain based on multidisciplinary diagnostics were evaluated. 15.6% of patients have given up on the participation in the study. It has been shown that the patients who dropped out of the study were significantly older (p=0.0411) than those who agreed to participate, but there was no difference in gender ratio (p=0.185) since the proportion of female patients prevailed. In an analysis of 84.4% of patients participating in the study, the elevated anxiety values were established (mean value on STAI 1 was 39.2 and STAI 2 was 41.1) and statistical significance was found in correlation between elevated anxiety and intensity of pain as shown on visual analogue scale on open mouth (p<0.0001). Compared to the age, the statistical significance was for STAI 1 (p=0.0097) but not for STAI 2 (p=0.5599). The most common form of therapy is Michigan stabilization splint: for disc displacement of temporomandibular joint (TMJ) in 38.9% of patients and in combination with physiotherapy in 18.7% of patients; for osteoarthritis of TMJ in 28.4% and in combination with physiotherapy in 26.4% of patients. The treatment with anticonvulsant drugs for trigeminal neuralgia predominates in 54.3% of patients, which is combined with acupuncture in 25.7% of patients and only acupuncture in 17.1% of patients. In this study, a multidisciplinary cooperation in initial diagnostics and differential was designed to develop subspecialist knowledge on orofacial pain.

No abstract

No abstract