Ex vivo analysis of cortical microarchitecture of the distal clavicle: implications for surgical management of fractures.

BACKGROUND: Cortical thickness and porosity are two main determinants of cortical bone strength. Thus, mapping variations in these parameters across the full width of the distal end of the clavicle may be helpful for better understanding the basis of distal clavicle fractures and for selecting optimal surgical treatment. METHODS: Distal ends of 11 clavicles (6 men, 5 women; age: 81.9 ± 15.1 years) were scanned by micro-computed tomography at 10-µm resolution. We first analyzed cortical thickness and porosity of each 500-µm-wide area across the superior surface of distal clavicle at the level of conoid tubercle in an antero-posterior direction. This level was chosen for detailed evaluation because previous studies have demonstrated its superior microarchitecture relative to the rest of the distal clavicle. Subsequently, we divided the full width of distal clavicle to three subregions (anterior, middle, and posterior) and analyzed cortical porosity, pore diameter, pore separation, and cortical thickness. RESULTS: We found the largest number of low-thickness and high-porosity areas in the anterior subregion. Cortical porosity, pore diameter, pore separation, and cortical thickness varied significantly among the three subregions (p < 0.001 p = 0.016, p = 0.001, p < 0.001, respectively). Cortex of the anterior subregion was more porous than that of the middle subregion (p < 0.001) and more porous and thinner than that of the posterior subregion (p < 0.001, p = 0.030, respectively). Interaction of site and sex revealed higher porosity of the anterior subregion in women (p < 0.001). The anterior subregion had larger pores than the middle subregion (p = 0.019), whereas the middle subregion had greater pore separation compared with the anterior (p = 0.002) and posterior subregions (p = 0.006). In general, compared with men, women had thinner (p < 0.001) and more porous cortex (p = 0.03) with larger cortical pores (p < 0.001). CONCLUSIONS: Due to high cortical porosity and low thickness, the anterior conoid subregion exhibits poor bone microarchitecture, particularly in women, which may be considered in clinical practice. LEVELS OF EVIDENCE: Level IV.

Testing of Different Scanning Protocols Used for Precise 3D-printing of Mandibular Models.

Multidetector computed tomography (MDCT) is often necessary to manufacture 3D-printed medical models (MMs) required for mandibular restoration due to trauma or malignant tumor. Although cone-beam computed tomography (CBCT) is a preferable method of mandibular imaging, additional scanning is often unjustified. To test whether a single radiologic protocol could be used for mandibular reconstructions, the human mandible was scanned with 6 MDCT and 2 CBCT protocols and later 3D-printed using a fused-deposition modelling technique. Then, we assessed linear measures on the mandible and compared them with MDCT/CBCT digital scans and 3D-printed MMs. Our data revealed that CBCT0.25 was the most precise protocol for manufacturing 3D-printed mandibular MMs, which is expected considering its voxel size. However, we noted that CBCT0.35 and Dental2.0H60s MDCT protocols were of comparable accuracy, indicating that this MDCT protocol could be a single radiologic protocol used to scan both donor and recipient regions required for mandibular reconstruction.

Relationship between nasal septum morphology and nasal obstruction symptom severity: computed tomography study / Relação entre a morfologia do septo nasal e a gravidade dos sintomas de obstrução nasal: estudo de tomografia computadorizada

Abstract Introduction The impact of the nasal septum morphology on the severity of obstruction symptoms has not been fully explored. Objective This study aimed to investigate whether the morphology of the deviated nasal septum assessed by computed tomography may explain nasal obstruction severity. Methods The study included 386 patients who were referred to the computed tomography examination of the paranasal sinuses. Patient selection criteria were the absence of facial anomalies, facial trauma, nasal surgery, and sinonasal tumors. Computed tomography images were used to estimate deviated nasal septum prevalence, the prevalence of Mladina's seven types of deviated nasal septum, and to measure the deviated nasal septum angle. Nasal obstruction severity was assessed by the nasal obstruction symptom evaluation, NOSE scale. The relationship between NOSE score, deviated nasal septum morphology, and deviated nasal septum angle was performed by a statistical regression model on the reduced sample of 225 patients. Results The prevalence of deviated nasal septum was 92.7%. Type 7 deviated nasal septum was the most frequent (34.2%) followed by type 5 (26.2%) and type 3 (23.6%). The worst NOSE scores were recorded in the type 2 deviated nasal septum (45.00 ± 28.28). The mean deviated nasal septum angle in patients with nasal obstruction was 8.5° ± 3.24. NOSE scores were not significantly associated with deviated nasal septum types and angles. Conclusion Patients with different types of deviated nasal septum have different NOSE scores. Computed tomography morphology of the deviated nasal septum could not fully explain the severity of nasal obstruction.

Resumo Introdução O impacto da morfologia do septo nasal na gravidade dos sintomas obstrutivos nasais ainda não foi totalmente explorado. Objetivo Investigar se a morfologia do desvio do septo nasal avaliada pela tomografia computadorizada pode explicar a gravidade da obstrução nasal. Método O estudo incluiu 386 pacientes encaminhados para exame tomográfico de seios paranasais. Os critérios de seleção dos pacientes foram: ausência de anomalias faciais, trauma facial, cirurgia nasal e tumores nasossinusais. Imagens de tomografia computadorizada foram usadas para estimar a prevalência de desvios do septo nasal, a prevalência dos sete tipos de desvios do septo nasal de Mladina e para medir o ângulo do desvio septal. A gravidade da obstrução nasal foi avaliada pela escala Nasal Obstruction Symptom Evaluation, NOSE. A relação entre o escore da NOSE, a morfologia e o ângulo do desvio septal foi verificada por um modelo de regressão estatística em uma amostra reduzida de 225 pacientes. Resultados A prevalência de desvios do septo nasal foi de 92,7%. O desvio septal do tipo 7 foi o mais frequente (34,2%), seguido do tipo 5 (26,2%) e do tipo 3 (23,6%). Os piores escores da escala NOSE foram registrados nos desvios septais tipo 2 (45,00 ± 28,28). O ângulo médio do desvio em pacientes com obstrução nasal foi de 8,5° ± 3,24. Os escores da escala NOSE não foram significativamente associados aos tipos e ângulos do desvio septal. Conclusão Pacientes com tipos diferentes de desvios do septo nasal apresentam diferentes escores na escala NOSE. A morfologia do desvio septal à tomografia computadorizada não conseguiu explicar totalmente a gravidade da obstrução nasal.

Relationship between nasal septum morphology and nasal obstruction symptom severity: computed tomography study.

INTRODUCTION: The impact of the nasal septum morphology on the severity of obstruction symptoms has not been fully explored. OBJECTIVE: This study aimed to investigate whether the morphology of the deviated nasal septum assessed by computed tomography may explain nasal obstruction severity. METHODS: The study included 386 patients who were referred to the computed tomography examination of the paranasal sinuses. Patient selection criteria were the absence of facial anomalies, facial trauma, nasal surgery, and sinonasal tumors. Computed tomography images were used to estimate deviated nasal septum prevalence, the prevalence of Mladina's seven types of deviated nasal septum, and to measure the deviated nasal septum angle. Nasal obstruction severity was assessed by the nasal obstruction symptom evaluation, NOSE scale. The relationship between NOSE score, deviated nasal septum morphology, and deviated nasal septum angle was performed by a statistical regression model on the reduced sample of 225 patients. RESULTS: The prevalence of deviated nasal septum was 92.7%. Type 7 deviated nasal septum was the most frequent (34.2%) followed by type 5 (26.2%) and type 3 (23.6%). The worst NOSE scores were recorded in the type 2 deviated nasal septum (45.00 ±â€¯28.28). The mean deviated nasal septum angle in patients with nasal obstruction was 8.5°â€¯±â€¯3.24. NOSE scores were not significantly associated with deviated nasal septum types and angles. CONCLUSION: Patients with different types of deviated nasal septum have different NOSE scores. Computed tomography morphology of the deviated nasal septum could not fully explain the severity of nasal obstruction.

Side asymmetry in nasal resistance correlate with nasal obstruction severity in patients with septal deformities: Computational fluid dynamics study.

OBJECTIVES: The objective of this study was to investigate the relationship between side asymmetry in nasal resistance (NR) and severity of the nasal airway obstruction (NAO) in patients with different types of nasal septal deformity (NSD). DESIGN: Computational fluid dynamics (CFD) study. SETTING: The study was conducted in a tertiary medical centre. PARTICIPANTS: The study included 232 patients, who were referred to the CT examination of the paranasal sinuses. Exclusion criteria were sinonasal and respiratory diseases that may interfere with the nasal obstruction. The presence and the type of NSD were recorded according to the Mladina's classification. MAIN OUTCOME MEASURES: The presence and severity of NAO in each patient were assessed by NOSE questionnaire. Eight computational models of the nasal cavity were created from CT scans. Models represented seven Mladina's NSD types and a straight septum of a symptomless patient. CFD calculated airflow partitioning and NR for each nasal passage. Side differences in NR were calculated by the equation ∆NR = NRleft  - NRright . The relationship between NOSE scores, airflow partitioning and side differences in NR was explored using Spearman's correlation analysis. RESULTS: Mladina's types of NSD showed differences in airflow partitioning and the degree of side asymmetry in NR. A significant positive correlation was detected between side differences in NR and NOSE scores (R = .762, P = .028). A significant negative correlation was found between the per cent of unilateral airflow and NR (R = -.524, P = .037). CONCLUSIONS: Our results demonstrated that side asymmetry in NR could explain differences in NAO severity related to the NSD type.

Radiological evaluation of Hyperostosis frontalis interna: is it of clinical importance?

Hyperostosis frontalis interna (HFI) presents irregular thickening of the frontal bone. Even though HFI is frequently seen during routine radiological imaging, it usually remains unrecorded owing to a common belief that it just represents an incidental finding or anatomical variant. Recent studies implied that HFI may be clinically relevant. Etiology of HFI is still debated, while presumptions are mainly based on altered sex steroids impact on skull bone growth. Some authors implied that frontal bone might be particularly affected by this condition due to specificity of its underlying dura. In this paper we present a 27-years old female patient with a treatment resistant headache. Head CT showed massive, irregular bony mass, with lobulated contours arising from the right frontal bone, but did not cross the fronto-parietal suture, spearing the superior sagittal sinus and skull midline. After surgery, histopathological analysis of the frontal bone sample in our patient showed thickening pattern similar to those described in micro-CT studies of HFI. Furthermore, in an attempt to test speculation of the possible role of estrogen in pathogenesis of HFI, we investigated the expression of α-estrogen receptors on dura of the frontal region. These analyses confirmed nuclear expression of estrogen on frontal region dural tissue, supporting previous speculation of the development mechanisms of HFI and contributing to a better understanding of this common condition of the frontal bone. Additionally, the presence of HFI may result in severe symptomatology, which could be misinterpreted and related to other disorders if HFI is not radiologicaly recognized and reported.

"Dangerous duo": Chronic nicotine exposure intensifies diabetes mellitus-related deterioration in bone microstructure - An experimental study in rats.

AIMS: Bony complications of diabetes mellitus (DM) are still insufficiently understood. Our aims were to analyze the individual and combined effects of chronic hyperglycemia and nicotine exposure on the femoral trabecular and cortical microarchitecture on a rat experimental model. MAIN METHODS: The micro-computed tomography based bone microstructural evaluation was performed on male Wistar rats divided into four groups: control (n = 7), experimentally-induced DM (n = 8), chronically exposed to nicotine (n = 9) and the DM group exposed chronically to nicotine (n = 9). KEY FINDINGS: Chronic hyperglycemia caused mild trabecular deterioration; yet, the combination of hyperglycemia and nicotine exposure showed more deleterious effects on the trabecular bone. Namely, the DM + nicotine group had significantly lower bone volume fraction, fewer and more rod-like shaped trabeculae, along with higher trabecular separation and lower connectivity than the control group (p < 0.05). Nicotine alone did not show any significant deterioration compared to the control group. DM and DM + nicotine groups had lower cortical porosity than control and nicotine groups (p < 0.05). Cortical thickness did not show any significant intergroup differences, whereas bone perimeter and the mean polar moment of inertia were reduced in DM + nicotine group. SIGNIFICANCE: Mild effects of chronic hyperglycemia on bone structure were accentuated by the chronic nicotine exposure, although nicotine alone did not cause any significant bone changes. That suggests a synergistic effect of hyperglycemia and nicotine on bone deterioration and increased propensity to fracture. Indeed, better understanding of risk factors driving bone structural deterioration is a precondition to limit the complications associated with DM.

Impact of the lower third molar presence and position on the fragility of mandibular angle and condyle: A Three-dimensional finite element study.

The aim of the present study was to investigate the influences of the presence and position of a lower third molar (M3) on the fragility of mandibular angle and condyle, using finite element analysis. From computed tomographic scans of a human mandible with normally erupted M3, two additional virtual models were generated: a mandibular model with partially impacted M3 and a model without M3. Two cases of impact were considered: a frontal and a lateral blow. The results are based on the chromatic analysis of the distributed von Mises and principal stresses, and calculation of their failure indices. In the frontal blow, the angle region showed the highest stress in the case with partially impacted M3, and the condylar region in the case without M3. Compressive stresses were dominant but caused no failure. Tensile stresses were recorded in the retromolar areas, but caused failure only in the case with partially impacted M3. In the lateral blow, the stress concentrated at the point of impact, in the ipsilateral and contralateral angle and condylar regions. The highest stresses were recorded in the case with partially impacted M3. Tensile stresses caused the failure on the ipsilateral side, whereas compressive stresses on the contralateral side.

Modeling of liver metastatic disease with applied drug therapy.

Colorectal carcinoma is acknowledged as the second leading cause of total cancer-related death in the European Region. The majority of deaths related to colorectal carcinoma are connected with liver metastatic disease. Approximately, in 25% of all patients, liver metastatic disease is diagnosed at the same time as the primary diagnosis, while up to a quarter of others would develop liver metastases in the course of the illness. In this study, we developed reaction-diffusion model and analyzed the effect of drug therapy on liver metastatic disease for a specific patient. Tumor volumes in specific time points were obtained using CT scan images. The nonlinear function for cell proliferation rate as well as data about clinically applied drug therapy was included in the model. Fitting procedure was used for parameter estimation. Good agreement of numerical and experimental results shows the feasibility and efficacy of the proposed system.

Skeletal manifestations of hydatid disease in Serbia: demographic distribution, site involvement, radiological findings, and complications.

Although Serbia is recognized as an endemic country for echinococcosis, no information about precise incidence in humans has been available. The aim of this study was to investigate the skeletal manifestations of hydatid disease in Serbia. This retrospective study was conducted by reviewing the medical database of Institute for Pathology (Faculty of Medicine in Belgrade), a reference institution for bone pathology in Serbia. We reported a total of 41 patients with bone cystic echinococcosis (CE) during the study period. The mean age of 41 patients was 40.9±18.8 years. In 39% of patients, the fracture line was the only visible radiological sign, followed by cyst and tumefaction. The spine was the most commonly involved skeletal site (55.8%), followed by the femur (18.6%), pelvis (13.9%), humerus (7.0%), rib (2.3%), and tibia (2.3%). Pain was the symptom in 41.5% of patients, while some patients demonstrated complications such as paraplegia (22.0%), pathologic fracture (48.8%), and scoliosis (9.8%). The pathological fracture most frequently affected the spine (75.0%) followed by the femur (20.0%) and tibia (5.0%). However, 19.5% of patients didn't develop any complication or symptom. In this study, we showed that bone CE is not uncommon in Serbian population. As reported in the literature, therapy of bone CE is controversial and its results are poor. In order to improve the therapy outcome, early diagnosis, before symptoms and complications occur, can be contributive.

Importance of early detection and follow-up of FLT3 mutations in patients with acute myeloid leukemia.

Mutations in the fms-like tyrosine kinase 3 (FLT3) gene, such as internal tandem duplication (FLT3/ITD) in the juxtamembrane domain and point mutations in the tyrosine kinase domain, are the most common abnormalities in acute myeloid leukemia (AML). FLT3/ITD and FLT3/D835 mutations were analyzed in 113 Serbian adult AML patients using polymerase chain reaction. Twenty patients were found to be FLT3/ITD positive (17.7%). The mutations occurred most frequently in M5 and M0 subtypes of AML. They were mainly associated with the normal karyotype. All patients harboring FLT3/ITD had a higher number of white blood cells than patients without it (p = 0.027). FLT3/ITD mutations were associated with lower complete remission (CR) rate (chi (2 )= 5.706; p = 0.017) and shorter overall survival (OS; Log rank = 8.76; p = 0.0031). As for disease-free survival, the difference between FLT3/ITD-positive and FLT3/ITD-negative patients was not statistically significant (Log rank = 0.78; p = 0.3764). In multivariate analysis, the presence of FLT3/ITD mutations was the most significant prognostic factor for both OS and CR rate (p = 0.0287; relative risk = 1.73; 95% CI = 1.06-2.82). However, in the group of patients with the intermediate-risk karyotype, the mere presence of FLT3/ITD was not associated with inferior clinical outcome. FLT3/D835 point mutation was found in four patients (3.5%) only. Follow-up of the FLT3/ITD-positive patients revealed stability of this mutation during the course of the disease. However, changes in the pattern of FLT3/D835 mutations in initial and relapsed AML were observed. Our results indicate an association of FLT3/ITD with the adverse outcome in AML patients treated with standard induction chemotherapy. Because FLT3/ITD mutation is a target for specific therapeutic inhibition, its early detection could be helpful in clinical practice.

Interpersonal violence at Lepenski Vir Mesolithic/Neolithic complex of the Iron Gates Gorge (Serbia-Romania).

The Mesolithic populations of the Danube River's Iron Gates Gorge (Serbia/Romania) spanned over 1,500 years (from before 7000 bc to around 5500 bc) in one of the most favorable foraging environments of Europe. Over most of these 1,500 years, the dominant economy was foraging, but farming was practiced by communities in the region from around 6500 bc. This research examines individuals from four sites on the Danube (Lepenski Vir, Vlasac, Padina, and Hajducka Vodenica) whose traumatic lesions can be most plausibly interpreted as resulting from violent interactions. Given over four hundred individuals buried at these sites (MNI = 418), the episodes of violent interactions were few and without evidence of a specific temporal pattern. They probably represent sporadic episodes of interpersonal conflict that do not support the notion of endemic warfare deemed typical of the Mesolithic, or elevated levels of interpersonal/intertribal conflict at the time of contact with farming communities. The difference in patterns of violence between the Mesolithic sites on the right bank of the Danube and a coeval site of Schela Cladovei on the left bank is explained in terms of differences in archaeological context, geographic location, and possibly specific local histories.