Health-related quality of life dynamics: modeling insights from immunotherapy.

BACKGROUND: Understanding health-related quality of life (HRQoL) dynamics is essential for assessing and improving treatment experiences; however, clinical and observational studies struggle to capture their full complexity. We use simulation modeling and the case of Chimeric Antigen Receptor T-cell therapy-a type of cancer immunotherapy that can prolong survival, but carries life-threatening risks-to study HRQoL dynamics. METHODS: We developed an exploratory system dynamics model with mathematical equations and parameter values informed by literature and expert insights. We refined its feedback structure and evaluated its dynamic behavior through iterative interviews. Model simulated HRQoL from treatment approval through six months post-infusion. Two strategies-reducing the delay to infusion and enhancing social support-were incorporated into the model. To dynamically evaluate the effect of these strategies, we developed four metrics: post-treatment HRQoL decline, recovery time to pre-treatment HRQoL, post-treatment HRQoL peak, and durability of the peak. RESULTS: Model captures key interactions within HRQoL, providing a nuanced analysis of its continuous temporal dynamics, particularly physical well-being, psychological well-being, tumor burden, receipt and efficacy of treatment, side effects, and their management. Model analysis shows reducing infusion delays enhanced HRQoL across all four metrics. While enhanced social support improved the first three metrics for patients who received treatment, it did not change durability of the peak. CONCLUSIONS: Simulation modeling can help explore the effects of strategies on HRQoL while also demonstrating the dynamic interactions between its key components, offering a powerful tool to investigate aspects of HRQoL that are difficult to assess in real-world settings.

Understanding how treatments affect patients' quality of life over time is crucial, but capturing the complex interactions of health factors poses a challenge for clinical and observational research. To overcome this, we have turned to simulation modeling, a method that allows for a more thorough exploration of these dynamics. Our study focuses on cancer immunotherapy, a treatment that, despite its potential to prolong survival, also comes with life-threatening risks. We evaluated the effectiveness of two strategies aimed at improving quality of life: reducing the time to treatment infusion and enhancing social support. These strategies were assessed across three different patient scenarios: those not initially eligible for treatment, patients experiencing a relapse, and patients showing a complete response. By using simulation modeling, we demonstrated how this approach can help explore the dynamics and interactions of various health factors and the impact of specific strategies.

Determining the optimum tumor control probability model in radiotherapy of glioblastoma multiforme using magnetic resonance imaging data pre- and post- radiation therapy.

Background: Glioblastoma multiforme (GBM) is the most common and malignant brain tumor. The current standard of care is surgery followed by radiation therapy (RT). Radiotherapy treatment plan evaluation relies on radiobiological models for accurate estimation of tumor control probability (TCP). This study aimed to assess the impact of obtained magnetic resonance imaging (MRI) data before and 12 weeks after RT to achieve the optimum TCP model to improve dose prescriptions in radiation therapy of GBM. Materials and Methods: In this quasi-experimental study, MR images and its relevant data from 30 patients consisting of 9 females and 21 males (mean age of 46.3 ± 15.8 years) diagnosed with GBM, whose referred for radiotherapy were selected. The data of age, gender, tumor size, volume, and signal intensity using analysis of MRI data pre- and postradiotherapy were used for calculating TCP. TCP was calculated from three common radiobiological models including Poisson, linear quadratic, and equivalent uniform dose. The impact of some radiobiological parameters on final TCP in all patients planned with three-dimensional conformal radiation therapy was obtained. Results: A statistically significant difference was found among TCP in Poisson model compared to the other two models (P < 0.001). Changes in tumor volume and size after treatment were statistically significant (P < 0.05). Different combinations of radiobiological parameters (α/ß and SF2 in all models) observed were meaningful (P < 0.05). Conclusion: The results showed that among TCP radiobiological models, the optimum is the Poisson. The results also identified the importance of TCP radiobiological models in order to improve radiotherapy dose prescriptions.

Joint frailty model for recurrent events and death in presence of cure fraction: Application to breast cancer data.

In many biomedical cohort studies, recurrent or repeated events for individuals can be terminated by a dependent terminal event like death. In this context, the time of death may be associated with the underlying recurrent process and there often exists the dependence between the occurrences of recurrent events. Moreover, there are some situations in which a portion of patients could be cured. In the present study, the term "cured" means that some patients may neither experience any recurrent events nor death induced by the disease under study. We proposed a joint frailty model in the presence of cure fraction for analysis of the recurrent and terminal events and estimated the effect of covariates on the cure rate and both aforementioned events concurrently. The use of two independent gamma distributed frailties in this model enabled us to consider both the dependence between the recurrences and the survival times and the interrecurrences dependence. The model parameters were estimated employing the maximum likelihood method for a piecewise constant and a parametric baseline hazard function. Our proposed model was evaluated by a simulation study and illustrated using a real data set on patients with breast cancer who had undergone surgery.

Effects of Neck Radiation on Result of Doppler Sonography of Carotid Arteries in Head and Neck Cancer Patients.

PURPOSE: The aim of this study was to assess the effects of neck radiation on the results of Doppler sonography of carotid arteries in head and neck cancer patients. METHODS: In this prospective, cross-sectional study, 25 consecutive patients with head and neck cancers were assessed for carotid artery stenosis (CAS) by carotid color Doppler sonography before external radiotherapy and six months after external radiotherapy. Main outcome measures were peak systolic velocity (PSVs), end-diastolic velocities (EDVs) of the internal carotid artery (ICA), ICA/common carotid (CCA) ratios, and degree of stenosis. RESULTS: The age of the enrolled patients at the initiation of radiotherapy was 57.9±11.8 years (mean±SD; range, 43-91 years), and only 4 (16%) of the 25 patients were female. The findings showed significant changes in the plaque degree and stenosis degree, and plaque size before and after external radiotherapy (P<0.05). Changes in degree of stenosis were significantly correlated with age (p=0.021). CONCLUSION: After neck irradiation changes in the carotid artery may occur and cause subsequent neurologic events.

Effect of Resin Infiltration Technique on Improving Surface Hardness of Enamel Lesions: A Systematic Review and Meta-analysis.

OBJECTIVE: White spot lesion (WSL) is recognized as the first clinical sign of enamel caries; it is a very critical phase because it can be prevented from progression to frank caries by changing the surrounding destructive environment. The present study was undertaken to systematically review the effect of resin infiltration (RI) technique on surface hardness (SH) of WSL. METHODS: Five electronic databases were searched with proper key words. Related titles and abstracts, up to October 2018, were screened, selected, and subjected to quality assessments. After collecting data, meta-analyses were carried out to compare the effect of RI with untreated WSL and sound enamel by using the STATA software. RESULTS: A total of 4567 articles were included in the study after initial search. Finally, 10 studies were reliable enough in methodology to be included in the study. Metadata analyses, carried out on 7 studies that compared SH of RI group with untreated samples, showed a significant increase in SH with 3.66 mean difference (95% confidence interval = 2.56‒4.77, Q value = 36.07, I2 = 83.4%). However, meta-analysis on 4 studies that compared SH of RI with sound enamel showed a significant decrease in SH with -2.35 overall mean difference (95% confidence interval = -3.91-0.98, P = .00, Q value = 31.75, I2 = 90.6%). CONCLUSION: The RI technique can enhance SH of WSL; however, regaining the SH of RI-treated WSLs similar to sound enamel is doubtful. Application of RI is more effective than other methods, including application of fluoride, enamel pro-varnish, adhesive, and colloidal silica infiltration for enhancing SH of WSLs.

Changes in lung volume parameters regarding the received dose in the lobes of the lungs after locoregional radiotherapy of breast cancer.

AIM: The purpose of this study was to evaluate ΔLVP and correlate them with MLD and V20 in the lobes of the lung. BACKGROUND: Radiation-induced lung injury after breast irradiation is controversial. The incidence of such an injury could have negative consequences on breast cancer patients. MATERIALS AND METHODS: Twenty-three women treated with Breast-conserving surgery, chemotherapy, and locoregional RT underwent body plethysmography pre-RT and 3 and 6 months post-RT. Statistical analysis was used to evaluate ΔLVP over time and relate them with MLD, V20, age, and concurrent hormonal therapy. RESULTS: LVP decreased after 3 months and then showed a slight improvement by returning partially to their pre-RT values after 6 months. The mean ΔLVP was -0.64% for one Gy increase of MLD and -0.34% for one percent increase of V20 after 3 months. After 6 months, only ΔVC showed 0.45% reduction with MLD in the upper lobe. Finally, there was no significant correlation between ΔLVP with respect to age and concurrent hormonal therapy. CONCLUSIONS: The results of this study showed that lung volume changes were not a cause for concern in breast cancer patients. There are three reasons to support this conclusion. Lung volume changes and percentage reductions in LVP for each Gy increase of MLD and each percentage increase of V20 in each lobe were small; patients were asymptomatic during the follow-up period; and LVP showed partial improvements after 6 months.

Effect of livergol on the improvement of fatty liver in patients with cancer undergoing irinotecan- and oxaliplatin-based chemotherapy regimen.

BACKGROUND: The aim of this study was to determine the effect of Livergol on the improvement of fatty liver in patients with cancer undergoing irinotecan- and oxaliplatin-based chemotherapy regimen. MATERIALS AND METHODS: This was an add-on nonrandomized clinical trial study on thirty selected eligible cancer patients undergoing irinotecan (8 patients) and oxaliplatin (22 patients) with diagnosed fatty liver disease-based liver ultrasonography, as well as alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Patients in each group received Livergol at a dose of 140 mg daily for 1 month. ALT and AST levels as well as grade of fatty liver were evaluated before and after intervention. RESULTS: In the oxaliplatin/Livergol group, 40% and 44.4% of patients who were in Grade 2 and 3 before intervention were altered to Grades 1 and 2, respectively (P = 0.005), and in irinotecan/Livergol group, the mentioned percentages were 80% and 66.7% (P = 0.014). The mean levels of ALT and AST enzymes were decreased in both groups after tacking Livergol; however, the observed decreases were not significantly different between groups. CONCLUSION: It was concluded that the adding of Livergol to oxaliplatin and irinotecan regimens significantly improved the fatty liver of patients and none of them was superior.

Plasmon-induced transparency based on a triangle cavity coupled with an ellipse-ring resonator.

In this paper, a novel compact plasmonic system is introduced to realize the phenomenon of plasmon-induced transparency. The proposed device consists of a triangle defect coupled with an ellipse-ring resonator based on a metal-insulator-metal platform. By the finite-difference time-domain method, the transmission characteristics are numerically studied in detail. In order to verify the simulation results, the coupled mode theory is utilized. In the following, the effect of geometrical parameters, namely, the major and minor radii of the ellipse-ring and the gap between cavities, are investigated. Moreover, the fundamental factors of transmission spectra including intrinsic Drude loss and refractive index of dielectric region are studied. As a result, the transmission peak is obtained near 70% and the full width at half-maximum is close to 28 nm. The sensitivity and figure of merit of the proposed structure are 860 nm/RIU and 31.6 RIU-1, respectively. The mentioned compact structure has the ability and potential to be used in integrated optical circuits like slow light devices, nanoscale filters and nanosensors.

Dosiomics-based detection of dose distribution variations in helical tomotherapy for prostate cancer patients: influence of treatment plan parameters.

The stability of dosiomics features (DFs) and dose-volume histogram (DVH) parameters for detecting disparities in helical tomotherapy planned dose distributions was assessed. Treatment plans of 18 prostate patients were recalculated using the followings: field width (WF) (2.5 vs. 5), pitch factor (PF) (0.433 vs. 0.444), and modulation factor (MF) (2.5 vs. 3). From each of the eight plans per patient, ninety-three original and 744 wavelet-based DFs were extracted, using 3D-Slicer software, across six regions including: target volume (PTV), pelvic lymph nodes (PTV-LN), PTV + PTV-LN (PTV-All), one cm rind around PTV-All (PTV-Ring), rectum, and bladder. For the resulting DFs and DVH parameters, the coefficient of variation (CV) was calculated, and using hierarchical clustering, the features were classified into low/high variability. The significance of parameters on instability was analyzed by a three-way analysis of variance. All DF's were stable in PTV, PTV-LN, and PTV-Ring (average CV ( CV ¯ )  ≤ 0.36). Only one feature in the bladder ( CV ¯  = 0.9), rectum ( CV ¯  = 0.4), and PTV-All ( CV ¯  = 0.37) were considered unstable due to change in MF in the bladder and WF in the PTV-All. The value of CV ¯ for the wavelet features was much higher than that for the original features. Out of 225 unstable wavelet features, 84 features had CV ¯  ≥ 1. The CVs for all the DVHs remained very small ( CV ¯ < 0.06). This study highlights that the sensitivity of DFs to changes in tomotherapy planning parameters is influenced by the region and the DFs, particularly wavelet features, surpassing the effectiveness of DVHs.

The Efficacy of Multi-Leaf Collimator in the Reduction of Cardiac and Coronary Artery Dose in Left-Sided Breast Cancer Radiotherapy.

Background: Multi-leaf collimator (MLC) is one of the efficient and cost-effective methods for protecting sensitive tissues around the target. This study aimed to evaluate the protective effect of MLC on the protection of sensitive organs in patients with left breast cancer. Materials and Methods: This study was performed on computed tomography (CT) scans of 45 patients with left breast cancer. Two treatment plans were completed for each patient. Only the heart and left lung were considered organs at risk in the first treatment plan, and in the second treatment plan, the left anterior descending artery (LAD) was also considered the organ at risk. It was covered as much as possible by the MLC. Dosimetric results of tumor and organ at risk (OARs) were extracted from the dose-volume histogram and compared. Results: The results showed that more LAD coverage by MLC leads to a significant reduction in the mean dose of OARs (P-value <0.05). The mean dose for heart, LAD, and left lung decreased by 11%, 7.4%, and 4.9%, respectively. The values of V5 (volume received the dose of 5 Gy) and V20 for the lung, V10, V25, and V30 for LAD, and V5, V20, V25, and V30 for the heart also decreased significantly (P-value <0.05). Conclusions: In general, better protection of LAD, heart, and lungs can be achieved by maximal shielding organs at risk by MLC in radiation therapy for patients with left breast cancer.

Dosimetric impact of different multileaf collimators on cardiac and left anterior descending coronary artery dose reduction.

Introduction: Radiotherapy (RT) may increase the dose of heart structure like left anterior descending coronary artery (LAD). The purpose of this paper was to evaluate the impact of various multileaf collimators (MLCs) in shielding organ at risks (OARs), especially LAD, of patients with left breast cancer. Materials and Methods: Forty-five patients with left breast cancer were selected. The treatment plans were created applying three techniques for all patients. In the first plan (uncovered LAD), the treatment plan was made without considering LAD as OARs. In the two other plans, two MLCs with different leaf widths (6.8 mm and 5 mm) were used to shield the LAD. For all plans, MLC was shielded as much of OAR as possible without compromising planning target volume (PTV) coverage. Dosimetric parameters of the heart, LAD, and ipsilateral lung were assessed. Results: Compared to other plans, the covered LAD plan 1(CL1) obtained lower lung, cardiac, and LAD doses with the same PTV coverage. On average, the mean heart dose decreased from 6.2 Gy to 5.4 Gy by CL1, and the average mean dose to the LAD was reduced from 36.4 Gy to 33.7 Gy, which was statistically significant. The average lung volume receiving >20 Gy was significantly reduced from 24.6% to 23.4%. Moreover, the results show that covered LAD plan 2(CL2) is less useful for shielding OARs compared to CL1. Conclusion: CL1 plans may reduce OAR dose for patients without compromising the target coverage. Hence, the proper implementation of MLC can decrease the side effects of RT.

Curcumin supplementation prevents cisplatin-induced nephrotoxicity: a randomized, double-blinded, and placebo-controlled trial.

Background and purpose: Cisplatin-induced nephrotoxicity (CIN) remains the most prevailing unfavorable influence and may affect its clinical usage. This study sought to explore the possible impacts of curcumin on preventing CIN in human subjects. Clinical design: The investigation was a placebo-controlled, double-blinded, randomized clinical trial conducted on 82 patients receiving nano-curcumin (80 mg twice daily for five days) or an identical placebo with standard nephroprotective modalities against CIN. Data was gathered on patients' demographics, blood, urinary nitrogen, creatinine (Cr) levels, urinary electrolytes, and urine neutrophil gelatinase-associated lipocalin (NGAL) levels in treatment and placebo groups, 24 h and five days after initiating the administration of cisplatin. Findings/Results: Both investigation groups were alike considering the demographic characteristics and clinical baseline data. Curcumin administration led to a significant improvement in blood-urine nitrogen (BUN). BUN, Cr, glomerular filtration rate (GFR), and the ratio of NGAL-to-Cr considerably altered during the follow-up periods. However, the further alterations in other indices, including urinary sodium, potassium, magnesium, NGAL values, and potassium-to-Cr ratio were not statistically noteworthy. The significant differences in the NGAL-to-Cr ratio between the two groups may indicate the potential protective impact of curcumin supplementation against tubular toxicity. Curcumin management was safe and well-accepted; only insignificant gastrointestinal side effects were reported. Conclusion and implications: Curcumin supplementation may have the potential to alleviate CIN and urinary electrolyte wasting in cancer patients. Future research investigating the effects of a longer duration of follow-up, a larger participant pool, and a higher dosage of curcumin are recommended.

Effect of fluoride dentifrices on the microhardness of deciduous enamel surfaces.

PURPOSE: To evaluate the changes in the enamel surface microhardness following the application of various suspensions of Crest and Pooneh toothpastes with and without fluoride. MATERIALS AND METHODS: Fifty-six enamel blocks of primary incisors were exposed to a pH-cycling regime consisting of demineralisation and remineralisation solution, then suspensions of the dentifrices Crest 1100, Crest 500, Pooneh 500, Pooneh without fluoride. Changes of the enamel surface microhardness in pre-demineralisation (initial), post-demineralisation (demineralised) and post-remineralisation (final) stages were measured for four groups and were analysed using the Student t test and one-way ANOVA. RESULTS: The percentages of changes in surface microhardness for Crest 1100, Crest 500, Pooneh 500 and Pooneh without fluoride were 45.4, 35.4, 28.6 and 23.7, respectively. CONCLUSION: Average changes of surface microhardness for Crest 1100 were significantly higher than Crest 500, Pooneh 500 and Pooneh without fluoride.

Investigation of HER-2 Expression an Its Correlation with Clinicopathological Parameters and Overall Survival of Esophageal Squamous Cell Carcinoma Patients.

BACKGROUND & OBJECTIVE: Human epidermal growth factor receptor 2 (HER-2) exhibits a vast range of expression in esophageal squamous cell carcinoma (ESCC) patients as a biomarker. This paper aimed to investigate HER-2 expression and clinicopathological parameters of esophageal SCC. METHODS: HER-2 expression was assessed in 102 ESCC patients by immunohistochemistry. The HER-2 staining intensity , according to the Gastric HER2 Biomarker1.0.0.1 version of the college of American pathologists (CAP) protocol for gastric and gastroesophageal junction cancers, was graded as 0 (no reactivity in any of the cancer cells' membranes); 1+ (pale or hardly noticeable reactivity in the membrane of cancer cells' cluster [≥ 5 neoplastic cells] regardless of the positive cancer cells' percentage); 2+ (weak-to-moderate complete, basolateral, or lateral membranous reactivity regardless of the positive cancer cells' percentage); and 3+ ( strong complete, basolateral, or lateral reactivity in the membrane of the cancer cell cluster regardless of the positive cancer cells' percentage).In this regard, 3+ scored samples were considered as positive. If HER-2 expression was scored 2+, an additional fluorescence in situ hybridization (FISH) was performed. Fisher's exact test was employed for investigating the correlation of HER-2 expression status with patients' clinicopathological characteristics (including age, gender, tumor location, stage, grade, infiltration level, venous invasion, lymphatic invasion, and tumor recurrence). Kaplan-Meier analysis was done for the patients' survival assessments. RESULTS: Five patients (~5%) were HER-2 positive and no significant association was observed between HER-2 expression and clinicopathological properties. In addition, HER-2 expression status exhibited no significant association with the patients' overall survival (P=0.9299). CONCLUSION: HER-2 is not a suitable prognostic biomarker for Iranian ESCC patients.

Evaluation of the Lung Dose in Three-dimensional Conformal Radiation Therapy of Left-Sided Breast Cancer: A Phantom Study.

BACKGROUND: Three-dimensional 3D-CRT: conformal radiation therapy is a selective modality in many radiotherapy centers for the treatment of breast cancer. One of the most common side effects of this method is radiation lung injury. Considering such an injury, lung dose deserves to be studied in depth. METHODS: Computed tomography scan of a node-positive left-sided breast cancer woman was used for generating a thorax phantom. Ten thermoluminescent dosimeters (TLDs) were distributed evenly in the left lung of the phantom, and the phantom was scanned. The optimal plan, including supraclavicular and tangential fields, was created by the treatment planning system (TPS). The results of TLD dose measurements at the selected points in the phantom were compared to TPS dose calculations. RESULTS: Lung doses calculated by TPS are significantly different from those measured by the TLDs (P = 0.007). The minimum and maximum differences were -0.91% and 4.46%, respectively. TLDs that were on the inner margin of the lung and breast tissue showed higher dose differences than the TLDs in the lung. CONCLUSION: The results of this study showed that TPS generally overestimated doses compared to TLD measurements due to incorrect beam modeling caused by contaminated electrons in the lung.

Effect of laser irradiation on push-out bond strength of dental fiber posts to composite resin core buildups: A systematic review and meta-analysis.

BACKGROUND: The bonding of fiber posts (FPs) to composite resin core buildups is a challenge due to limited penetration of resin to the polymeric matrix of FPs. This review article tries to answer this question: "What are the effects of laser surface treatment of FPs, compared to other surface roughening methods, on push-out bond strength (PBS) of FPs bonded to composite resin core buildups?" METHODS: Searches were run in seven electronic databases with a focus on proper key words. Related titles and abstracts, up to February 2019, were screened, selected, read and subjected to quality assessments. RESULTS: After the initial search, a total of 2635 articles were included in the study. Finally, 6 studies were reliable enough in methodology to be included. All the studies were in vitro with a total of 359 samples. Er:YAG (-0.05, 95% CI: -2.96 to 2.86; P = 0.97) and Er,Cr:YSGG (0.84, 95% CI: -0.12 to 1.81; P = 0.08) treated samples showed no significant overall mean differences in final PBS compared to the control groups. Moreover, pretreatment with Er,Cr:YSGG laser and sandblasting with 50 µm alumina showed an overall mean difference of -0.42 for PBS (95% CI: -1.23 to 0.39) with no significant differences. CONCLUSIONS: Laser irradiation of FPs seems to provide no significant increase in PBS values of FPs bonded to composite resin core buildups. Effects of surface treatment of FPs with laser irradiation and sandblasting with 50 µm alumina might be similar in increasing the final PBS, either.

Radiobiological Evaluation of Three Common Clinical Radiotherapy Techniques Including Combined Photon-Electron, Tangential Beams and Electron Therapy in Left-Sided Mastectomy Patients.

BACKGROUND: The aim of this study was radiobiological evaluation of different radiotherapy (RT) techniques, namely, combined photon-electron, two tangential photon beams, and electron therapy which are commonly used for treatment of mastectomy patients. MATERIALS AND METHODS: The mentioned techniques were planned on the computed tomography (CT) images of a chest phantom, using TiGRT treatment planning system (TPS). The TPS dose calculations were verified using Thermo Luminescence dosimeters (TLD) measurements. Dose-volume histogram (DVH) of the plans was generated in the TPS, and also tumor control probability (TCP) and normal tissue complication probability (NTCP) values were calculated using DVH data for each technique. For TCP and NTCP modeling, Poisson Linear-Quadatric (PLQ) and Lyman-Kutcher-Burman (LKB) models were used, respectively. RESULTS: The TCPs for the chest wall, internal mammary nodes, supraclavicular nodes, and axilla for the combined photon-electron was 90%, 90%, 90%, and 65%, respectively, which was higher compared to tangential beams (up to 11%, 11%, 5%, and 5%, respectively) and the electron therapy (up to 11%, 11%, 33%, and 23%, respectively) Whereas the NTCPs of the tangential beams for ipsilateral and contralateral lungs, heart, and chest wall-lung interface was 4%, 1%, 3%, and 5.6%, respectively. These NTCP values were considerably lower than electron therapy (up to 42%, 66%, and 40% and 30%, respectively) and combined photon-electron (up to 55%, 75%, 50%, and 20%, respectively) methods. CONCLUSION: Tangential beam is suggested for treating mastectomy patients, due to sufficient value of TCP, and also lower NTCP compared to the other techniques such as electron therapy and combined photon-electron.

Pulp Response following Direct Pulp Capping with Dentin Adhesives and Mineral Trioxide Aggregate; An Animal Study.

INTRODUCTION: Pulp vitality and its continuous dentin prodution are essential for long-term success of direct pulp capping (DPC). The aim of present study was to evaluate the histopathological response of the canine pulp following DPC using either different dentin adhesive resins (DAR), calcium hydroxide (CH) or mineral trioxide aggregate (MTA). METHODS AND MATERIALS: DPC was done on 72 dog's teeth using 6 types of dental materials (n=12) (4 types of DAR, white MTA and CH). Therefore, six healthy dogs were anesthetized and 2 teeth from each dog were allocated to either type of mentioned DPC agents. The dental pulps were exposed mechanically by drilling in the center of class V cavities. The different types of capping materials included DARS (Clearfil S3 Bond, Optibond FL, Single Bond and Clearfil SE Bond), white MTA and CH. After 7, 21 and 63 days, two dogs were euthanized in each interval. Microscopic evaluations were done according to following criteria: intensity of inflammation, presence of necrosis and formation of hard tissue. The recorded data were analyzed by the Kruskal-Wallis, Friedman, Cochran's and Fisher's exact tests using SPSS software version 12 at significant level of 0.05. RESULTS: No significant differences were found regarding necrosis among DPC materials (P>0.05). However, MTA caused higher amount of hard tissue formation after 63 days in comparison with 21 days. CONCLUSION: MTA provided the highest degree of hard tissue formation after 63 days. However, further studies should be performed for administering a definitive material.

Hard tissue reaction to mineral trioxide aggregate and experimental root-end filling material in guinea pig mandibles.

BACKGROUND/PURPOSE: Root-end filling materials are used to fill and seal the root apex during periradicular surgery. Mineral trioxide aggregate (MTA) is a widely-used material because of its particular characteristics. Cold ceramic (CC) is an experimental material that has been recently introduced. The purpose of this study was to compare bone tissue response to CC and MTA in an animal model. MATERIALS AND METHODS: Forty-five male guinea pigs (weighing 750-850 g) were anesthetized with 10 mg/kg ketamine HCL and 12 mg/kg xylazine. A triangular incision of around 15 mm was prepared in the posterior site along the symphysis in both right and left sides of the mandible. A 3 mm × 3 mm diameter cylindrical hole was prepared in each side using a trephine. Two Teflon cylindrical tube applicators were filled with white MTA and CC and inserted into the defects separately. Histopathological evaluation of the specimens was completed after 2 weeks and 12 weeks. The extent of inflammation was recorded and analyzed using the Mann-Whitney U test and SPSS software version 12 at a significance level of 0.05. RESULTS: MTA and CC produced moderate and mild hard tissue responses respectively after 2 weeks and 12 weeks. No significant differences were found in the distribution of the responses between the two groups at either time point. CONCLUSION: Both CC and MTA demonstrated biocompatibility with minor adverse impact on hard tissue and healing recovery after 12 weeks.

Bone Repair with Differentiated Osteoblasts from Adipose-derived Stem Cells in Hydroxyapatite/Tricalcium Phosphate In vivo.

BACKGROUND: Recently, tissue engineering has developed approaches for repair and restoration of damaged skeletal system based on different scaffolds and cells. This study evaluated the ability of differentiated osteoblasts from adipose-derived stem cells (ADSCs) seeded into hydroxyapatite/tricalcium phosphate (HA-TCP) to repair bone. METHODS: In this study, ADSCs of 6 canines were seeded in HA-TCP and differentiated into osteoblasts in osteogenic medium in vitro and bone markers evaluated by reverse transcription polymerase chain reaction (RT-PCR). Scanning electron microscopy (SEM) was applied for detection of cells in the pores of scaffold. HA-TCP with differentiated cells as the test group and without cells as the cell-free group were implanted in separate defected sites of canine's tibia. After 8 weeks, specimens were evaluated by histological, immunohistochemical methods, and densitometry test. The data were analyzed using the SPSS 18 version software. RESULTS: The expression of Type I collagen and osteocalcin genes in differentiated cells were indicated by RT-PCR. SEM results revealed the adhesion of cells in scaffold pores. Formation of trabecular bone confirmed by histological sections that revealed the thickness of bone trabecular was more in the test group. Production of osteopontin in extracellular matrix was indicated in both groups. Densitometry method indicated that strength in the test group was similar to cell-free group and natural bone (P > 0.05). CONCLUSIONS: This research suggests that ADSCs-derived osteoblasts in HA-TCP could be used for bone tissue engineering and repairing.