Morphological, anatomical, radiological and clinical features of Mladina type 6 nasal septum deformations in humans.

PURPOSE: The objective of this study was to prove the higher frequency of the type 6 deformations overall compared to the results obtained by conventional diagnostic methods, such as computed tomography images and clinical examination. METHODS: The study was performed at the Institute of Anatomy, where a total of 114 randomly selected skulls were examined. The skulls were then scanned in a fixed position using the cone-beam technique (CBCT). The literature epidemiological data of the clinical incidence of type 6 in studies that also used Mladina classification were obtained. RESULTS: There was a statistically significant difference (p < 0.0001) in the frequency of type 6 deformation as diagnosed by visual inspection (22.8%) and computed tomography (7.9%). The frequency obtained by CT imaging amounted 7.9% and was almost the same as the results obtained by a clinical examination which varied between 9 and 11%. CONCLUSIONS: The frequency of type 6 nasal septal deformation is higher by visual inspection of the skulls than by computed tomography imaging at a level of significance of 0.05. The incidence of type 6 findings on coronal CT images of paranasal sinuses is approximately the same as that found with anterior rhinoscopy. Type 6, visible or concealed; probably have one-fourth to one-fifth people in population, so the number of clinically overlooked and/or unrecognized types 6 is much greater than we thought it to be.

Pharmacogenomics at the center of precision medicine: challenges and perspective in an era of Big Data.

Pharmacogenomics (PGx) is one of the core elements of personalized medicine. PGx information reduces the likelihood of adverse drug reactions and optimizes therapeutic efficacy. St Catherine Specialty Hospital in Zagreb/Zabok, Croatia has implemented a personalized patient approach using the RightMed® Comprehensive PGx panel of 25 pharmacogenes plus Facor V Leiden, Factor II and MTHFR genes, which is interpreted by a special counseling team to offer the best quality of care. With the advent of significant technological advances comes another challenge: how can we harness the data to inform clinically actionable measures and how can we use it to develop better predictive risk models? We propose to apply the principles artificial intelligence to develop a medication optimization platform to prevent, manage and treat different diseases.

Dasatinib-induced nephrotic syndrome: a case of phenoconversion.

We present the case of a 33-year-old chronic myeloid leukemia (CML) female patient, in whom the occurrence of nephrotic syndrome, during the treatment with tyrosine kinase activity inhibitors (TKIs), was potentially influenced by transient phenoconversion. Seven years after the CML diagnosis in 2004 and complete response, the patient experienced pain in the mandible and extremities. After this, imatinib was replaced by nilotinib, but generalized maculopapular rash was presented and successfully treated with antihistamines. The therapy was then discontinued due to planned pregnancy, and the patient experienced a relapse of CML with BCR-ABL/ABL1 transcripts of 18.9%. Dasatinib was introduced, and CML was in remission. Two years later, urine protein levels (6.19 g/L) and erythrocyte sedimentation rate were elevated (ESR=90 mm/3.6 ks). The patient was diagnosed with nephrotic syndrome. With dasatinib dose reduction, urine protein level returned to the reference range. In order to determine the best genotype-guided therapy, the patient underwent pharmacogenomic testing, showing a homozygous CYP3A4 genotype *1/*1, associated with extensive metabolizer (EM) enzyme phenotype, typical for normal rates of drug metabolism for TKIs. However, this was inconsistent with nephrotic syndrome occurrence. A possible explanation would be CYP3A4 EM genotype coding a poor metabolizer enzyme phenotype, leading to the drug accumulation in the patient's blood. This transient phenoconversion can be explained by inflammation with elevated ESR during nephrotic syndrome. This case shows that a broader approach that recognizes genetic, clinical, and epigenomic factors is required for a quality decision on the personalized therapy regimen.