Attention 3D U-NET for dose distribution prediction of high-dose-rate brachytherapy of cervical cancer: Direction modulated brachytherapy tandem applicator.

BACKGROUND: Direction Modulated Brachytherapy (DMBT) enables conformal dose distributions. However, clinicians may face challenges in creating viable treatment plans within a fast-paced clinical setting, especially for a novel technology like DMBT, where cumulative clinical experience is limited. Deep learning-based dose prediction methods have emerged as effective tools for enhancing efficiency. PURPOSE: To develop a voxel-wise dose prediction model using an attention-gating mechanism and a 3D UNET for cervical cancer high-dose-rate (HDR) brachytherapy treatment planning with DMBT six-groove tandems with ovoids or ring applicators. METHODS: A multi-institutional cohort of 122 retrospective clinical HDR brachytherapy plans treated to a prescription dose in the range of 4.8-7.0 Gy/fraction was used. A DMBT tandem model was constructed and incorporated onto a research version of BrachyVision Treatment Planning System (BV-TPS) as a 3D solid model applicator and retrospectively re-planned all cases by seasoned experts. Those plans were randomly divided into 64:16:20 as training, validating, and testing cohorts, respectively. Data augmentation was applied to the training and validation sets to increase the size by a factor of 4. An attention-gated 3D UNET architecture model was developed to predict full 3D dose distributions based on high-risk clinical target volume (CTVHR) and organs at risk (OARs) contour information. The model was trained using the mean absolute error loss function, Adam optimization algorithm, a learning rate of 0.001, 250 epochs, and a batch size of eight. In addition, a baseline UNET model was trained similarly for comparison. The model performance was evaluated on the testing dataset by analyzing the outcomes in terms of mean dose values and derived dose-volume-histogram indices from 3D dose distributions and comparing the generated dose distributions against the ground-truth dose distributions using dose statistics and clinically meaningful dosimetric indices. RESULTS: The proposed attention-gated 3D UNET model showed competitive accuracy in predicting 3D dose distributions that closely resemble the ground-truth dose distributions. The average values of the mean absolute errors were 1.82 ± 29.09 Gy (vs. 6.41 ± 20.16 Gy for a baseline UNET) in CTVHR, 0.89 ± 1.25 Gy (vs. 0.94 ± 3.96 Gy for a baseline UNET) in the bladder, 0.33 ± 0.67 Gy (vs. 0.53 ± 1.66 Gy for a baseline UNET) in the rectum, and 0.55 ± 1.57 Gy (vs. 0.76 ± 2.89 Gy for a baseline UNET) in the sigmoid. The results showed that the mean absolute error (MAE) for the bladder, rectum, and sigmoid were 0.22 ± 1.22 Gy (3.62%) (p = 0.015), 0.21 ± 1.06 Gy (2.20%) (p = 0.172), and -0.03 ± 0.54 Gy (1.13%) (p = 0.774), respectively. The MAE for D90, V100%, and V150% of the CTVHR were 0.46 ± 2.44 Gy (8.14%) (p = 0.018), 0.57 ± 11.25% (5.23%) (p = 0.283), and -0.43 ± 19.36% (4.62%) (p = 0.190), respectively. The proposed model needs less than 5 s to predict a full 3D dose distribution of 64 × 64 × 64 voxels for any new patient plan, thus making it sufficient for near real-time applications and aiding with decision-making in the clinic. CONCLUSIONS: Attention gated 3D-UNET model demonstrated a capability in predicting voxel-wise dose prediction, in comparison to 3D UNET, for DMBT intracavitary brachytherapy planning. The proposed model could be used to obtain dose distributions for near real-time decision-making before DMBT planning and quality assurance. This will guide future automated planning, making the workflow more efficient and clinically viable.

The association between enteral nutrition with survival of critical patients with COVID-19.

BACKGROUND: Coronavirus disease 2019 (COVID-19) results in several complications and mortality in intensive care unit (ICU) patients. Limited studies have investigated the effect of enteral nutrition (EN) on the survival of COVID-19 patients in the ICU. The aim of this study was to investigate the association of EN with biochemical and pathological indices associated with mortality in ICU patients with COVID-19. METHODS: This case-control study was conducted on 240 patients with COVID-19 hospitalized in the ICU including 120 eventual nonsurvived as the cases and 120 survived patients as the controls. All of the patients received EN as a high protein high volume or standard formula. Data on general information, anthropometric measurements, and the results of lab tests were collected. RESULTS: The recovered patients received significantly more high protein (60.8% vs. 39.6%, p = .004) and high volume (61.6% vs. 42.3%, p = .005) formula compared to the nonsurvived group. Mortality was inversely associated with high volume (odds ratio [OR]: 0.45 confidence interval [CI]95%, p = .008) and high protein (OR: 0.42 CI95%, p = .003) formula. The results remained significant after adjusting for age and sex. Further adjustment for underlying diseases, smoking, body mass index, and the acute physiology and chronic health evaluation II (APACHE II) score did not change the results. CONCLUSION: The findings of the study showed that there was a significant inverse association between mortality and high volume and high protein formula in patients with COVID-19. Further investigation is warranted.

Re-irradiation of recurrent head and neck cancers using pulsed reduced dose rate radiotherapy: An institutional series.

PURPOSE/OBJECTIVE(S): Pulsed reduced dose rate (PRDR) radiation (RT) is a re-irradiation (Re-RT) technique that potentially overcomes dose/volume constraints in the setting of previous RT. There is minimal data for its use for recurrent or secondary primary head and neck squamous cell carcinoma (HNSCC). In this study, we report preliminary data from our institution of a consecutive cohort of HNSCC patients who received PRDR Re-RT. MATERIALS/METHODS: Nine patients received PRDR Re-RT from August 2020 to January 2023 and had analyzable data. Intensity modulated RT was used for treatment delivery and a wait time between 20 cGy arc/helical deliveries was used to achieve the effective low dose rate. Data collected included patient demographic information, prior interventions, diagnosis, radiation therapy dose and fractionation, progression free survival, overall survival, and toxicity rates. RESULTS: The median time to PRDR-RT from completion of initial RT was 13 months (range, 6-50 months). All but one patient underwent salvage surgery prior to PRDR-RT. The median follow-up after Re-RT was 7 months. The median OS from PRDR-RT was 7 months (range, 1-32 months). Median PFS was 7 months (range, 1-32 months). One patient (11.1 %) had acute grade 3 toxicity, and two patients (22.2 %) had late grade 3 toxicities. There were no grade 4+ toxicities. CONCLUSION: PRDR Re-RT is a feasible treatment strategy for patients with recurrent or second primary HNSCC. Initial findings from this retrospective review suggest reasonable survival outcomes and potentially improved toxicity; prospective data is needed to establish the safety and efficacy of this technique.

Evaluating dose distributions of high dose rate 60Co brachytherapy in an asymmetric tumor: A comparison of different designs of vaginal cylindrical applicators.

The aim of this study is to evaluate organ-at-risk (OAR) doses obtained from different designs of intracavitary cylinder applicators during high-dose-rate (HDR) brachytherapy of an asymmetric vaginal tumor. Dose distributions around five cylinder applicators were obtained using the Geant4 toolkit. Three of these applicators are commercially available: single-channel, multi-channel, and shielded. Additionally, two proposed sub-configurations were evaluated: (I) a combination of the multichannel applicator with a central shield and (II) a dynamically modulated cylinder (DMC). The dose distributions of the proposed applicators were compared to those of the single-channel cylinder applicator. The results showed that using a cylindrical applicator with a higher degree of freedom in plan optimization can improve OAR, sparing up to 60% for the rectum and 20% for the bladder. In conclusion, this work suggests using a new design of a cylindrical applicator to enhance the therapeutic ratio of brachytherapy for asymmetric and irregularly shaped vaginal tumors.

The association between obesity with treatment duration, ICU length of stay and the risk of death in critically ill patients with COVID-19.

BACKGROUND: Despite the confirmed association between higher BMI with increased risk of the acute respiratory distress syndrome (ARDS), the association between obesity with mortality in critically ill patients with coronavirus disease 2019 (COVID-19) is not clear. The present study aimed to investigate the association between obesity with treatment duration, ICU length of stay, and the risk of death in critically ill patients with COVID-19. METHODS: This case-control study was performed on 223 patients with COVID-19 including 148 surviving patients as the control group and 75 eventually dead patients as the case group in Rasht, Iran. Data on demographic factors, comorbidities, anthropometric measurements, the length of hospitalization and the mortality were obtained from patients' medical records. RESULTS: The mortality rate was significantly associated with weight (OR = 1.04, 95% CI: 1.002-1.083, p = .04), but not with BMI after adjustments for age, gender, length of stay in ICU, chronic diseases and smoking. The results did not change after further adjustments for biochemical and pathological factors. CONCLUSIONS: Weight was positively associated with mortality after controlling for confounding variables. Further studies should consider the patient's body composition such as fat mass to establish the relationship between obesity and COVID-19 outcomes.

Human osteosarcoma cells in response to ELF-MF: Morphological remodeling compared to cell proliferation.

Purpose: The present study aimed to assess the effects of extremely low-frequency electromagnetic fields (ELF-MF) on structural changes of human osteosarcoma cells by analyzing the stained cytoskeleton for assessing the relationship between the fractal dimension parameter and proliferation rate of radiation-induced cells. Materials and Methods: In this study, 2-mT magnetic fields with various waveforms, including sinusoidal, triangular, and pulsed shapes, were employed to determine the biological effects of ELF-EMF on the human osteosarcoma MG-63 cell line. All experiments were performed in two modes: continuous exposure at 3 h and fractionated irradiations at 3 consecutive days. Afterward, the proliferation assay was implemented for assessing the cell proliferation in each group. Moreover, immunofluorescence staining and confocal imaging were performed to determine the cell shape index. Furthermore, fractal dimension analysis was carried out by processing morphological images. Results: The proliferation and shape index parameters of radiation-induced osteosarcomas significantly decreased compared with non-irradiated cells. In addition, fractal dimensions significantly increased following fractionated exposure at 3 consecutive days. Conclusions: Assessing the fractal dimensions can be considered as a new morphological index for the prognosis of the structural remodeling of human osteosarcoma cells in response to fractionated irradiation of ELF-MF. In addition, various waveforms induce a similar effect on morphological remodeling and cell proliferation.

A systematic review of the normal tissue complication probability models and parameters: Head and neck cancers treated with conformal radiotherapy.

This systematic review study aims to provide comprehensive data on different radiobiological models, parameters, and endpoints used for calculating the normal tissue complication probability (NTCP) based on clinical data from head and neck cancer patients treated with conformal radiotherapy. A systematic literature search was carried out according to the PRISMA guideline for the identification of relevant publications in six electronic databases of Embase, PubMed, Scopus, and Google Scholar to July 2022 using specific keywords in the paper's title and abstract. The initial search resulted in 1368 articles for all organs for the review article about the NTCP parameters. One hundred and seventy-eight articles were accepted for all organs with complete parameters for the mentioned models and finally, 20 head and neck cancer articles were accepted for review. Analysis of the studies shows that the Lyman-Kutcher-Burman (LKB) model properly links the NTCP curve parameters to the postradiotherapy endpoints. In the LKB model for esophagus, the minimum, and maximum corresponding parameters were reported as TD50 = 2.61 Gy with grade ≥3 radiation-induced esophagitis endpoints as the minimum TD50 and TD50 = 68 Gy as the maximum ones. nmin = 0.06, nmax = 1.04, mmin = 0.1, and mmax = 0.65, respectively. Unfortunately, there was not a wide range of published articles on other organs at risk like ear or cauda equina except Burman et al. (Fitting of normal tissue tolerance data to an analytic function. Int J Radiat Oncol Biol Phys Ther. 1991;21:123-135). Findings suggest that the validation of different radiobiological models and their corresponding parameters need to be investigated in vivo and in vitro for developing a more accurate NTCP model to be used for radiotherapy treatment planning optimization.

Dosimetric comparison between microSelectron iridium-192 and flexi cobalt-60 sources in high-dose-rate brachytherapy using Geant4 Monte Carlo code.

Purpose: Manufacturing of miniaturized high activity iridium-192 (192Ir) sources have been made a market preference in modern brachytherapy. Smaller dimensions of the sources are flexible for smaller diameter of the applicators, and it is also suitable for interstitial implants. Presently, cobalt-60 (60Co) sources have been commercialized as an alternative to 192Ir sources for high-dose-rate (HDR) brachytherapy, since 60Co source have an advantage of longer half-life comparing with 192Ir source. One of them is the HDR 60Co Flexisource manufactured by Elekta. The purpose of this study was to compare the TG-43 dosimetric parameters of HDR flexi 60Co and HDR microSelectron 192Ir sources. Material and methods: Monte Carlo simulation code of Geant4 (v.11.0) was applied. Following the recommendations of AAPM TG-43 formalism report, Monte Carlo code of HDR flexi 60Co and HDR microSelectron 192Ir was validated by calculating radial dose function, anisotropy function, and dose-rate constants in a water phantom. Finally, results of both radionuclide sources were compared. Results: The calculated dose-rate constants per unit air-kerma strength in water medium were 1.108 cGy h-1U-1 for HDR microSelectron 192Ir, and 1.097 cGy h-1U-1 for HDR flexi 60Co source, with the percentage uncertainty of 1.1% and 0.2%, respectively. The values of radial dose function for distances above 22 cm for HDR flexi 60Co source were higher than that of the other source. The anisotropic values sharply increased to the longitudinal sides of HDR flexi 60Co source, and the rise was comparatively sharper to that of the other source. Conclusions: The primary photons from the lower-energy HDR microSelectron 192Ir source have a limited range and are partially attenuated when considering the results of radial and anisotropic dose distribution functions. This implies that a HDR flexi 60Co radionuclide could be used to treat tumors beyond the source compared with a HDR microSelectron 192Ir source, despite the fact that 192Ir has a lower exit dose than HDR flexi 60Co radionuclide source.

The association between vitamin D intake with inflammatory and biochemical indices and mortality in critically ill patients with COVID-19: A case-control study.

BACKGROUND: The coronavirus disease-2019 (COVID-19) has become a worldwide health issue with widespread hospitalization and dependence on the intensive care unit (ICU). Vitamin D has a key role in modulating immune cells and modulating the inflammatory responses. This study aimed to investigate the association of vitamin D supplementation with inflammatory, biochemical, and mortality indices in critically ill patients with COVID-19. METHODS: This case-control study was conducted on critically ill COVID-19 patients hospitalized in the ICU including the survived >30 day patients as the case group and dead patients as the control group. The status of vitamin D supplementation and inflammatory and biochemical indices of the patients were retrieved from the medical records. Logistic regression method was used to assess the association between 30 days survival and vitamin D supplement intake. RESULTS: Compared to the group of COVID-19 patients who died in <30 day, the survived patients had a lower eosinophile level (2.2 ± 0.5 vs. 6 ± 0.0, p < .001) and higher vitamin D supplementation duration (9 ± 4.4 vs. 3.3 ± 1.9 day, p = .001). Vitamin D supplementation had a positive association with survival in COVID-19 patients (OR: 1.98, 95% CI: 1.15-3.40, p < .05). The association remained significant after adjustments fot age, sex, underlying diseases, and smoking. CONCLUSION: Vitamin D supplementation in critically ill patients with COVID-19 has the potential to increase survivability within the first 30 days of hospitalization.

Bystander Response Following High-Dose X-irradiation; Time-dependent Nature of GammaH2AX Foci and Cell Death Consequences.

Background: The paradigm shifts in target theory could be defined as the radiation-triggered bystander response in which the radiation deleterious effects occurred in the adjacent cells. Objective: This study aims to assess bystander response in terms of DNA damage and their possible cell death consequences following high-dose radiotherapy. Temporal characteristics of gH2AX foci as a manifestation of DNA damage were also evaluated. Material and Methods: In this experimental study, bystander response was investigated in human carcinoma cells of HeLa and HN5, neighboring those that received high doses. Medium transfer was performed from 10 Gy-irradiated donors to 1.5 Gy-irradiated recipients. GammaH2AX foci, clonogenic and apoptosis assays were investigated. The gH2AX foci time-point study was implemented 1, 4, and 24 h after the medium exchange. Results: DNA damage was enhanced in HeLa and HN5 bystander cells with the ratio of 1.27 and 1.72, respectively, which terminated in more than two-fold clonogenic survival decrease, along with gradual apoptosis increase. GammH2AX foci temporal characterization revealed maximum foci scoring at the 1 h time-point in HeLa, and also 4 h in HN5, which remained even 24 h after the medium sharing in higher level than the control group. Conclusion: The time-dependent nature of bystander-induced gH2AX foci as a DNA damage surrogate marker was highlighted with the persistent foci at 24 h. considering an outcome of bystander-induced DNA damage, predominant role of clonogenic cell death was also elicited compared to apoptosis. Moreover, the role of high-dose bystander response observed in the current work clarified bystander potential implications in radiotherapy.

Fully automated clinical target volume segmentation for glioblastoma radiotherapy using a deep convolutional neural network.

Purpose: Target volume delineation is a crucial step prior to radiotherapy planning in radiotherapy for glioblastoma. This step is performed manually, which is time-consuming and prone to intra- and inter-rater variabilities. Therefore, the purpose of this study is to evaluate a deep convolutional neural network (CNN) model for automatic segmentation of clinical target volume (CTV) in glioblastoma patients. Material and methods: In this study, the modified Segmentation-Net (SegNet) model with deep supervision and residual-based skip connection mechanism was trained on 259 glioblastoma patients from the Multimodal Brain Tumour Image Segmentation Benchmark (BraTS) 2019 Challenge dataset for segmentation of gross tumour volume (GTV). Then, the pre-trained CNN model was fine-tuned with an independent clinical dataset (n = 37) to perform the CTV segmentation. In the process of fine-tuning, to generate a CT segmentation mask, both CT and MRI scans were simultaneously used as input data. The performance of the CNN model in terms of segmentation accuracy was evaluated on an independent clinical test dataset (n = 15) using the Dice Similarity Coefficient (DSC) and Hausdorff distance. The impact of auto-segmented CTV definition on dosimetry was also analysed. Results: The proposed model achieved the segmentation results with a DSC of 89.60 ± 3.56% and Hausdorff distance of 1.49 ± 0.65 mm. A statistically significant difference was found for the Dmin and Dmax of the CTV between manually and automatically planned doses. Conclusions: The results of our study suggest that our CNN-based auto-contouring system can be used for segmentation of CTVs to facilitate the brain tumour radiotherapy workflow.

Efficacy of Nanoparticles in dose enhancement with high dose rate of Iridium-192 and Cobalt-60 radionuclide sources in the Treatment of Cancer: A systematic review.

ABSTRACTS: A key challenge in radiation therapy is to maximize the radiation dose to cancer cells while minimizing damage to healthy tissues. In recent years, the introduction of remote after-loading technology such as high-dose-rate (HDR) brachytherapy becomes the safest and more precise way of radiation delivery compared to classical low-dose-rate (LDR) brachytherapy. However, the axially symmetric dose distribution of HDR with single channel cylindrical applicator, the physical "dead-space" with multichannel applicators, and shielding material heterogeneities are the main challenges of HDR brachytherapy. Thus, this review aimed to quantitatively evaluate the dose enhancement factor (DEF) produced by high atomic number nanoparticles (NPs) which increases the interaction probability of photons mainly through the photoelectric effect induced in the great number of atoms contained in each nanoparticle. The NPs loaded to the target volume create a local intensification effect on the target tissue that allows imparting the prescribed therapeutic dose using lower fluxes of irradiation and spare the surrounding healthy tissues. An electronic database such as PubMed/Medline, Embase, Scopus, and Google Scholar was searched to retrieve the required articles. Unpublished articles were also reached by hand from available sources. The dose is increased using the high atomic number of nanoparticle elements under the high dose iridium radionuclide whereas the cobalt-60 radionuclide source did not. However, much work is required to determine the dose distribution outside the target organ or tumor to spare the surrounding healthy tissues for the iridium source and make compressive work to have more data for the cobalt source.

A Novel Workflow with a Customizable 3D Printed Vaginal Template and a Direction Modulated Brachytherapy (DMBT) Tandem Applicator for Adaptive Interstitial Brachytherapy of the Cervix.

A novel clinical workflow utilizing a direction modulated brachytherapy (DMBT) tandem applicator in combination with a patient-specific, 3D printed vaginal needle-track template for an advanced image-guided adaptive interstitial brachytherapy of the cervix. The proposed workflow has three main steps: (1) pre-treatment MRI, (2) an initial optimization of the needle positions based on the DMBT tandem positioning and patient anatomy, and a subsequent inverse optimization using the combined DMBT tandem and needles, and (3) rapid 3D printing. We retrospectively re-planned five patient cases for two scenarios; one plan with the DMBT tandem (T) and ovoids (O) with the original needle (ND) positions (DMBT + O + ND) and another with the DMBT T&O and spatially reoptimized needles (OptN) positions (DMBT + O + OptN). All retrospectively reoptimized plans have been compared to the original plan (OP) as well. The accuracy of 3D printing was verified through the image registration between the planning CT and the CT of the 3D-printed template. The average difference in D2cc for the bladder, rectum, and sigmoid between the OPs and DMBT + O + OptNs were -8.03 ± 4.04%, -18.67 ± 5.07%, and -26.53 ± 4.85%, respectively. In addition, these average differences between the DMBT + O + ND and DMBT + O + OptNs were -2.55 ± 1.87%, -10.70 ± 3.45%, and -22.03 ± 6.01%, respectively. The benefits could be significant for the patients in terms of target coverage and normal tissue sparing and increase the optimality over free-hand needle positioning.

Comparison of normal tissue doses in deep inspiration breath-hold and free breathing methods for radiotherapy of left-sided breast cancer using 4D-XCAT digital phantom.

Purpose: To evaluate normal lung and heart tissue doses for treatment of left-sided breast cancer in deep inspiration breath-hold (DIBH) and free breathing (FB) as a function of breast size and diaphragm displacement using 4D-XCAT digital phantom in a simulation study. Materials and Methods: 4D-XCAT digital phantom was used to create 36 left-sided breast cancer digital phantom datasets with different breast height (BH) of 40, 50, and 60 mm, breast length (BL) of 16, 17, and 18 mm, and diaphragm excursion of 20, 25, 30, and 35 mm. For each dataset, DIBH and FB treatment plans were prepared using planning computerized radiotherapy-three dimensional (PCRT-3D) treatment planning system (TPS) with superposition computational algorithm. Dose differences in DIBH and FB plans were assessed in terms of mean lung dose (MLD), the lung volume receiving ≤20 Gy (V20), normal tissue complication probability (NTCP) of the lung, mean heart dose (MHD), and the heart volume receiving ≤30 (V30). Results: DIBH reduced mean dose and V20 and NTCP of the lung in all cases, by up to 4.37 Gy, 7.62%, and 18.95%. Mean dose and V30 of the heart were also significantly reduced by 5.02 Gy and 8.23%. Conclusions: The use of DIBH for left-sided breast cancer radiotherapy offers excellent possibilities for sparing critical normal tissue without compromising radiation dose to the target.

Effects of supplementation with low-dose group B vitamins on clinical and biochemical parameters in critically ill patients with COVID-19: a randomized clinical trial.

BACKGROUND: : This study aimed to check the effect of supplementation with low-dose group B vitamins on clinical and biochemical parameters on patients with coronavirus disease 2019 (COVID-19). RESEARCH DESIGN AND METHOD: : This double-blind, randomized clinical trial was carried out on 85 critically ill patients with COVID-19. All patients received high protein prescriptions of 30 kcal/kg/d by enteral nutrition. The intervention group (n = 40) received vitamin B complex, including thiamine (10 mg), riboflavin (4 mg), nicotinamide (40 mg), and dexpanthenol (6 mg). The control group received similar nutritional supports, except for group B vitamins. Assessments were carried out at baseline and after 2 weeks of intervention. RESULTS: : Vitamin B supplementation had no effects on the biochemical and pathological parameters including kidney function, arterial blood gas parameters, Glasgow coma scale, cell blood count, and serum electrolytes of the intervention group compared with the control group. The 30-day mortality was insignificantly lower in the intervention group than in the control group (83.3% against 96.1%, P = 0.07). CONCLUSIONS: The mortality rate of patients with COVID-19 might be improved by low-dose vitamin B supplementation.

Predictors of Intensive Care Unit Admission in Patients with Confirmed Coronavirus Disease 2019: A Cross-Sectional Study.

Background: The coronavirus disease 2019 (COVID-19) has become the leading source of pneumonia outbreaks in the world. The present study aimed to compare the condition of intensive care unit (ICU) and non-ICU COVID-19 patients in terms of epidemiological and clinical features, laboratory findings, and outcomes in three cities across Iran. Methods: In a cross-sectional study, 195 COVID-19 patients admitted to five hospitals across Iran during March-April 2020 were recruited. Collected information included demographic data, laboratory findings, symptoms, medical history, and outcomes. Data were analyzed using SPSS software with t test or Mann-Whitney U test (continuous data) and Chi square test or Fisher's exact test (categorical variables). P<0.05 was considered statistically significant. Results: Of the 195 patients, 57.4% were men, and 67.7% had at least one comorbidity. The prevalence of stroke, chronic obstructive pulmonary disease, and autoimmune diseases was higher in ICU than in non-ICU patients (P=0.042, P=0.020, and P=0.002, respectively). Compared with non-ICU, ICU patients had significantly higher white blood cell (WBC) count (P=0.008), cardiac troponin concentrations (P=0.040), lactate dehydrogenase levels (P=0.027), erythrocyte sedimentation rates (P=0.008), and blood urea nitrogen (BUN) (P=0.029), but lower hematocrit levels (P=0.001). The mortality rate in ICU and non-ICU patients was 48.1% and 6.1%, respectively. The risk factors for mortality included age>40 years, body mass index<18 Kg/m2, hypertension, coronary artery disease, fever, cough, dyspnea, ST-segment changes, pericardial effusion, and a surge in WBC and C-reactive protein, aspartate aminotransferase, and BUN. Conclusion: A high index of suspicion for ICU admission should be maintained in patients with positive clinical and laboratory predictive factors.

A Dosimetric evaluation of a high dose rate cobalt-60 brachytherapy source using shielded, single and multi-channel cylinder applicators for gynecological cancers.

Vaginal brachytherapy is a standard method for preventing the recurrences of malignancies in the treatment of gynecological cancers. Cylindrical applicators are usually employed in high dose rate cobalt-60 source brachytherapy after abdominal hysterectomy or bilateral salpingo-oophorectomy treatment. The aim of this study is to conduct an assessment of dosimetric properties of single channel, multichannel, and shielded cylinder applicators. This study utilizes a pelvis phantom with three different volumes of bladder and rectum to perform dose measurement around the cylindrical applicators. GAFCHROMIC EBT3 model film was used to measure dose distributions in water phantom around the bladder, rectum, applicator, and CTV. In order to properly compare the performance of the shielded applicator with multichannel and single channel applicators, we consider the both cases of a one-sided CTV and two CTVs placed on both sides of the vagina. Dose-volume histograms analysis shows no statistically significant difference in tumoral region for the two types of CTV between cylindrical applicators. The V120%, V100% and D95% values of target volume were 47.36%. 91.46%, and 3.99Gy for multi-channel cylinder applicator, 60.2%, 95.02%, and 3.99Gy for single channel cylinder applicator, respectively. Statistical analysis reports D0.1cc, D1cc, and D2cc for the multichannel applicator demonstrates a significant dose reduction in bladder compared with single channel. The V120%, V100%, and D95% values of target volume were 55.50%. 97.90%, and 3.91Gy for multi-channel cylinder applicator with four active channels (MCC-4), 41.56%, 92.10%. and 4.13Gy for shielded cylinder applicator, respectively. Statistical analysis reports D0.1cc, D1cc and D2cc for the MCC-4 demonstrates a noticeable dose reduction in bladder and rectum compared with Shielded channel. The results indicate that employing multichannel applicator in vaginal high dose rate cobalt-60 source brachytherapy can reduce the received dose to organs at risk without any significant loss of received dose in CTV, which is contributed to its asymmetric or symmetric dose distribution that depend on which channels are activated.

Osteogenic differentiation of adipose-derived stem cells on dihydroartemisinin electrospun nanofibers.

BACKGROUND: Adipose tissue-derived stem cells (ASCs) are promising candidate in stem cell therapies, and maintaining their stemness potential is vital to achieve effective treatment. Natural-based scaffolds have been recently attracted increasing attention in nanomedicine and drug delivery. In this study, Dihydroartemisinin (DHART)-loaded polycaprolactone collagen nanofibers (PCL/Col NFs) were constructed as effective biocompatible scaffolds through adjusting the proportions of hydrophobic/ hydrophilic polymers for enhanced osteoblastic differentiation of human adipose-derived stem cells (hADSCs). RESULTS: The designed NFs were characterized through FTIR, XRD, TGA, FE-SEM, and tensile testing. DHART-loaded PCL/Col electrospun NFs provide an ideal solution, with the potential of sustained drug release as well as inhibition of drug re-crystallization. Interestingly, inhibiting DHART re-crystallization can improve its bioavailability and provide a more effective therapeutic efficacy. Besides, the data set found through FE-SEM, MTT, PicoGreen, qPCR, and alkaline phosphatase (ALP) assays revealed the improved adhesion and proliferation rate of hADSCs cultured on PCL/Col/DHART (5%) NFs after 14 and 21 days of incubation. CONCLUSIONS: These findings confirmed the potential of the designed NF scaffolds for sustained/controlled release of DHART therapeutic molecules toward bone tissue regeneration and engineering.

Investigation the effect of a magnetic field on the dose distribution of I-125, Ir-192, Yb-169, and Co-60 brachytherapy sources by Monte Carlo simulation.

Magnetic resonance imaging (MRI) during brachytherapy may alter the dose distribution of radioactive sources implanted in the tumor. This study investigates the impact of a magnetic field of 1.5 T, 3 T, and 7 T strengths on the dose distribution of high dose rate Co-60, Ir-192, and Yb-169, and low dose rate I-125 sources, using Geant4 Monte Carlo toolkit. After validating the simulation results by calculating the AAPM-TG43 dosimetric parameters, seven sources of each radioisotope were simulated in a water phantom, and their dose distributions were compared under the influence of a magnetic field. The simulation results indicate that using Co-60 brachytherapy under the MRI guidance is not recommended. Furthermore, the impact of a magnetic field of up to 7 T strength on the dose distribution of Ir-192, Yb-169, and I-125 sources is negligible, provided that there is no air pocket near brachytherapy sources.

Evaluation of Capability and Relationship of Different Radiobiological Endpoints for Radiosensitivity Prediction in Human Tumor Cell Lines Compared with Clonogenic Survival.

Background: Establishing a predictive assay of radiosensitivity (as an appropriate, practical and cost-effective method) has been challenging. Objective: The purpose of this study is to evaluate the capability and relationship of various endpoints, including GammaH2AX, micronuclei; and apoptosis in determining the human tumor cell lines radiosensitivities compared with clonogenic survival. Material and Methods: In an experimental in-vitro study, the response of carcinoma cell lines of HN5 and HeLa to 2 Gy of 6 MV photon beam was investigated via various assays. Results: Survival fraction at 2 Gy (SF2) of HeLa and HN5 was indicated as 0.42 ± 0.06 and 0.5 ± 0.03 respectively, proposing more radioresistance of HN5. This finding was confirmed with "2 Gy apoptosis enhancement ratio" which was 1.77 and 1.42 in HeLa and HN5. The increased levels of DNA DSBs were observed after irradiation; significant in HeLa with enhancement rate of 19.24. The micronuclei formation followed an ascending trend post irradiation; but with the least difference between two cells. Although the relationship between micronuclei and clonogenic survival was moderate (R2 = 0.35), a good correlation was observed between apoptosis and clonogenic survival (R2 = 0.71). Conclusion: The results of studied endpoints agreed with the SF2, highlighting their capabilities in radiosensitivity prediction. In terms of the enhancement ratio, gammaH2AX foci scoring could be a valid indicator of radiosensitivity but not the exact surrogate marker of survival because no correlation was observed. Moreover, considering the chief determents comprising lack of time and money, the apoptotic induction might be an appropriate indicator with the best correlation coefficient.