In situ gelling nanosuspension as an advanced platform for fluticasone propionate nasal delivery.

In this work we present the development of in situ gelling nanosuspension as advanced form for fluticasone propionate nasal delivery. Drug nanocrystals were prepared by wet milling technique. Incorporation of drug nanocrystals into polymeric in situ gelling system with pectin and sodium hyaluronate as constitutive polymers was fine-tuned attaining appropriate formulation surface tension, viscosity and gelling ability. Drug nanonisation improved the release profile and enhanced formulation mucoadhesive properties. QbD approach combining formulation and administration parameters resulted in optimised nasal deposition profile, with 51.8% of the dose deposited in the middle meatus, the critical region in the treatment of rhinosinusitis and nasal polyposis. Results obtained in biocompatibility and physico-chemical stability studies confirmed the leading formulation potential for safe and efficient nasal corticosteroid delivery.

Imaging in chronic rhinosinusitis: A systematic review of MRI and CT diagnostic accuracy and reliability in severity staging.

BACKGROUND: Computerized tomography (CT) severity scores are frequently used as an objective staging tool in chronic rhinosinusitis (CRS). Magnetic resonance imaging (MRI) has also been proposed as a valid option in CRS imaging. PURPOSE: The aim of this systematic review was to briefly present the recent developments on sinus imaging utilized in clinical practice with regard to diagnostic accuracy of imaging and severity staging in CRS according to evidence-based medicine (EBM) principles. MATERIAL AND METHODS: This review paper has been assembled following PRISMA guidelines. A PubMed and Scopus (EMBASE) search using CRS, "severity staging", "diagnostic accuracy "and "imaging "resulted with 80 results. Of these, only 12 (59%) contained original data, constituting the synthesis of best-quality available evidence. RESULTS: CT is the most commonly used imaging technique for the severity staging of CRS, but a question of higher cumulative radiation dose should be taken into consideration when repeating CT examinations in evaluating treatment efficacy. MRI may be a complementary diagnostic and staging tool, especially when repeated examinations are required, or when paediatric CRS patients are evaluated. The severity staging system may be improved to better correlate with subjective scores. CONCLUSIONS: MRI may be utilized as a staging tool with comparable diagnostic accuracy, using the same staging systems as with CT examinations.

OROFACIAL PAIN - DIAGNOSTIC AND THERAPEUTIC CHALLENGES.

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 co-operation in initial diagnostics and differential was designed to develop subspecialist knowledge on orofacial pain.

An internal carotid artery pseudoaneurysm with neck hematoma: A rare cause of a life-threatening neck mass mimicking an abscess.

A neck mass has a broad and complex differential diagnosis, generally divided into neoplastic, congenital and inflammatory categories. An internal carotid artery hemorrhage with pseudoaneurysm formation is a very rare entity that may resemble other common conditions in the differential diagnosis. Large, expanding or symptomatic pseudoaneurysm is critical to efficiently diagnose and manage, due to risk of life-threatening hemorrhage. We present a case of an adult male patient with clinical and laboratory signs of severe neck cellulitis and a large gradually increasing neck mass, primarily suggestive of an abscess. Neck CT and MRI imaging revealed the presence of a disruption of the internal carotid artery resulting in a large hematoma and formation of pseudoaneurysm. A multidisciplinary team of interventional radiologists and ENT surgeons successfully treated the patient by endovascular placement of stents and subsequent surgical drainage. Awareness of such a rare, life-threatening condition and efficient multidisciplinary teamwork are essential for patient management.

Prostatic Artery Embolization as a New Option in the Treatment of Lower Urinary Tract Symptoms in Benign Prostatic Hyperplasia - Current Evidence.

Prostatic artery embolization is a minimally invasive endovascular treatment that improves lower urinary tract symptoms in men with benign prostatic hyperplasia. Although further randomized studies and long-term evidence is still needed for this method to be fully incorporated into treatment guidelines for benign prostatic hyperplasia, current studies show that this method can be an effective and safe alternative in patients with a significantly enlarged prostate gland who are not good surgical candidates. Therefore, we present the theory, technical details and potential benefits of this method as we review the current evidence on prostatic artery embolization.

Evaluation of the Head Multislice Computed Tomography Scan in Emergency Department.

The aim of the study was to examine the prevalence of head injuries, acute stroke and brain tumors obtained from computed tomography (CT) scans in the emergency department (ED) during a one-year period. We also assessed the potential effect of seasons on the occurrence of stroke, head trauma and tumors found on CT scans, expressed in monthly intervals. This retrospective review included all patients that underwent emergency head CT from the hospital database. A total of 3888 head CT examinations were performed in adult patients presenting to ED and 1424 CT scans had at least one pathologic finding meeting diagnostic criteria for the study. Of the total number of CT scans analyzed, acute stroke was identified in 552 (14.19%), head trauma in 660 (16.97%), and brain tumor in 212 (5.45%) patients. Head trauma was more commonly found in males (n=465, 70.45%) than in females (n=195, 29.54%). Acute stroke was slightly more common in males than in females. Brain tumors were more frequently found in female patients. There were monthly variations in the number of head injuries and acute stroke diagnosed during the study period. Men and elderly patients were found to account for the greatest number of traumatic head injuries and therefore are at the highest risk of possible brain injury.

CORRELATION BETWEEN MAMMOGRAPHY DETECTED BREAST ARTERIAL CALCIFICATIONS AND LIFESTYLE RISK FACTORS.

The aim of the study was to investigate the association between some lifestyle-attributable risk factors of atherosclerosis, such as body mass index (BMI), oral contraceptives, hormone replacement therapy, smoking and alcohol consumption with breast arterial calcification (BAC) and its intensity on mammograms, and to assess the impact of these lifestyle risk factors on mammography findings of BAC. This prospective study included 300 women aged 47-69, i.e. a group of 149 women with BAC on mammograms and control group of 151 women without BAC. Self-reported BMI, use of oral contraceptives, hormone replacement therapy, smoking and alcohol consumption were recorded by medical interview. The presence of BAC and its intensity on mammography was compared according to the presence of high BMI and use of hormone therapy, smoking and alcohol consumption. The results showed the highest proportion of smokers (28.9%) in the group with mild BAC as compared with the groups without calcification (14.6%) and with intense calcification (12.1%). Women taking oral contraceptives had a higher level of calcified breast arteries but no significant between-group difference was found for high BMI, hormone therapy and alcohol consumption. Thus, study results showed the mammographic finding of BAC to be inadequate to identify women with some lifestyle-attributable risk factors such as BMI, hormone replacement therapy, smoking and alcohol consumption.

INITIAL SYMPTOMATIC PITUITARY METASTASIS IN A PATIENT WITH PROSTATE FOAMY GLAND CARCINOMA: TAILORING SAFE AND EFFECTIVE THERAPY.

Metastases to pituitary gland are unusual and mostly asymptomatic, presenting with local symptoms in one of ten patients, and only 3%-5% of them are of prostate origin. Here we report and evaluate the effectiveness and safety of multimodal treatment in a patient with pituitary metastasis of a prostate foamy gland carcinoma. A 78-year-old male patient presented with blurred vision and headache without a previous history of malignancy. Magnetic resonance imaging scans revealed a large sellar mass, with infiltration of the surrounding structures. Maximal transsphenoidal reduction of pituitary metastasis was performed, with a histologic finding of metastatic prostate foamy gland adenocarcinoma. Evaluation of the prostate specific antigen revealed a very high level (1461 ng/mL) and foamy gland carcinoma was found on prostate needle biopsy. The patient received 3D conformal external beam radiotherapy with 6 MV photons to the sellar and parasellar region with a tumor dose of 44 Gy, followed by androgen deprivation therapy. Follow up magnetic resonance imaging done after radiotherapy showed shrinkage of the tumor process, with rapid prostate specific antigen decline to 0.3 ng/mL. The visual function was fully established and headache resolved. On the last follow up 14 months after the diagnosis, the patient was alive and free from clinical signs of disease. Tailored treatment, including limited radiotherapy in a higher palliative dose, in a patient with foamy gland symptomatic pituitary metastatic disease resulted in good local and systemic control of the disease. In older male patients with clinical and/or radiologic characteristics suggestive of metastatic pituitary disease, the prostate specific antigen test should be included as part of the work-up.

Primary uterine cervical cancer: correlation of preoperative magnetic resonance imaging and clinical staging (FIGO) with histopathology findings.

The most commonly used staging system for cervical cancer is based on the International Federation of Gynaecology and Obstetrics (FIGO) staging system. Magnetic resonance imaging (MRI) has been accepted as the optimal tool for evaluation of the main prognostic factors and selection of therapeutic strategy. The purpose of this study was to compare the preoperative clinical examination FIGO staging findings with MRI and postoperative pathology report in females with primary cancer of the cervix. The study prospectively included 46 females consecutively hospitalized at the Department of Gynaecology and Obstetrics at the "Sestre milosrdnice" University Hospital Center in Zagreb. Interviews, clinical examination, transvaginal ultrasound and MRI were performed in all patients. In selected patients the surgical procedure was done and the correlation of clinical findings according to FIGO classifications, MRI and histopathological findings was completed. According to FIGO classification, positive clinical findings for stage IIA were found in 26/46 (55.5%) and stage IIB in 20/46 (44.5%)patients. FIGO MR modified classification confirmed stage IIA in 30/46 (66.6%) and stage IIB in 16/46 (33.4%) patients. Surgery (Wertheim radical hysterectomy with bilateral pelvic and selective para-aortic lymphadenectomy) was performed in 33/46 (71%) patients with clinically, MR, cytologically and pathohistologically confirmed findings of cervical cancer: 26 patients with IIA clinically FIGO stage and 7 with IIB stage. MRI examination proved better than clinical examination in staging of cervical carcinoma with 90.9% versus 79.0% accuracy rate. We suggest the application of the following MR protocol in all clinically staged FIGO IIA and IIB patients: T1W, T2WI and postcontrast dynamic T1WI after 3 and 60 seconds and after 5 minutes, performed on 1.5T MR machine.

Radiographic validation of manual functional analysis of temporomandibular joint osteoarthritis.

The finding of osteoarthritis of temporomandibular joint (TMJ) obtained by clinical diagnosis, i.e. manual functional analysis (MFA) and the finding obtained by magnetic resonance imaging (MRI) as the gold standard were compared in 30 patients (mean age 52.6) diagnosed with osteoarthritis, selected out of 140 consecutive patients diagnosed with a TMJ disorder by MRI. The clinical parameters were symptoms of pain in the TMJ region, crepitations, and absence of clicking, which was confirmed by manual examinations as part of MFA. A positive MRI finding included flattening, subchondral degenerative changes with or without intact cortical bone, osteophytes and subchondral degenerative cysts of joint surfaces. The validity of MFA for osteoarthritis was as follows: sensitivity 0.38, specificity 0.91, positive predictive value (PPV) 0.77 and negative predictive value (NPV) 0.65. MRI examination revealed disk displacement (DD) without reduction in 12 (40.00%) patients and DD with reduction in one (3.33%) patient. The finding of passive compressions for the osteoarthritis diagnosis depending on DD showed sensitivity of 0.29, specificity of 0.95, PPV 0.67 and NPV 0.78. Although MFA significantly improves validity of clinical diagnosis when differentiating a myogenic from TMJ disorder, clinical determination of osteoarthritis is not satisfactory. Nonspecific clinical signs and symptoms accompanied by predominant pain in the TMJ on dynamic but not on passive manual examinations cannot help differentiate DD from osteoarthritis.

Intrathyroid parathyroid carcinoma with intrathyroidal metastasis to the contralateral lobe: source of diagnostic and treatment pitfalls.

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.