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Nevin Manimala Statistics

Monte Carlo simulation of conical collimators for stereotactic radiosurgery with a 6 MV flattening-filter-free photon beam

Med Phys. 2021 Mar 14. doi: 10.1002/mp.14837. Online ahead of print.

ABSTRACT

PURPOSE: Conical collimators, or cones, are tertiary collimators that attach to a radiotherapy linac and are suited for the stereotactic radiosurgery treatment of small brain lesions. The small diameter of the most used cones makes difficult the acquisition of the dosimetry data needed for the commissioning of treatment planning systems. Although many publications report dosimetric data of conical collimators for stereotactic radiosurgery, most of the works use different setups, which complicates comparisons. In other cases, the cone output factors reported do not take into account the effect of the small cone diameter on the detector response. Finally, few data exist on the dosimetry of cones with flattening-filter-free beams from modern linac models. This work aims at obtaining a dosimetric characterization of the conical collimators manufactured by Brainlab AG (Munich, Germany) in a 6 MV FFF beam from a TrueBeam STx linac (Varian Medical Systems).

METHODS: Percentage depth dose curves, lateral dose profiles and cone output factors were obtained using Monte Carlo simulations for the cones with diameters of 4, 5, 6, 7.5, 8, 10, 12.5, 15, 17.5, 20, 25, and 30 mm. The simulation of the linac head was carried out with the PRIMO Monte Carlo software, and the simulations of the cones and the water phantom were run with the general-purpose Monte Carlo code PENELOPE. The Monte Carlo model was validated by comparing the simulation results with measurements performed for the cones of 4 mm, 5 mm, and 7.5 mm of diameter using a stereotactic field diode, a microDiamond detector and EBT3 radiochromic film. In addition, for those cones, simulations and measurements were done for comparison purposes, by reproducing the experimental setups from the available publications.

RESULTS: The experimental data acquired for the cones of 4, 5, and 7.5 mm validated the developed Monte Carlo model. The simulations accurately reproduced the experimental depths of maximum dose and the dose ratio at 20 cm and 10 cm depth (PDD20/10 ). A good agreement was obtained between simulated and experimental lateral dose profiles: the differences in the full-width at half maximum were smaller than 0.2 mm, and the differences in the penumbra 80%-20% were smaller than 0.25 mm. The difference between the simulated and the average of the experimental output factors for the cones of 4, 5, and 7.5 mm of diameter was 0.0%, 0.0% and 3.0%, respectively, well within the statistical uncertainty of the simulations (4.4% with coverage factor k = 2). It was also found that the simulated cone output factors agreed within 2% with the average of output factors reported in the literature for a variety of setup conditions, detectors, beam qualities, and cone manufacturers.

CONCLUSION: A Monte Carlo model of cones for stereotactic radiosurgery has been developed and validated. The cone dosimetry dataset obtained in this work, consisting of percentage depth doses, lateral dose profiles and output factors, is useful to benchmark data acquired for the commissioning of cone-based radiosurgery treatment planning systems.

PMID:33715167 | DOI:10.1002/mp.14837

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Nevin Manimala Statistics

Relationship between de novo lipogenesis and serum sex hormone-binding globulin in humans

Clin Endocrinol (Oxf). 2021 Mar 14. doi: 10.1111/cen.14459. Online ahead of print.

ABSTRACT

OBJECTIVE: Obesity and liver fat are associated with decreased levels of serum sex hormone-binding globulin (SHBG). Laboratory studies suggest that hepatic de novo lipogenesis (DNL) is involved in the downregulation of SHBG synthesis. The aim of the present study was to address the role of DNL on serum SHBG in humans.

DESIGN: A cross-sectional study examining the association between DNL, measured by stable isotopes, and serum SHBG, stratified by sex.

PARTICIPANTS: Healthy men (n=34) and women (n=21) were combined from two cross-sectional studies. Forty-two percent of participants had hepatic steatosis, and the majority were overweight (62%) or obese (27%).

RESULTS: DNL was inversely associated with SHBG in women (β: -0.015, 95%CI: -0.030;0.000), but not in men (β: 0.007, 95%CI: -0.005;0.019) (p for interaction=0.068). Adjustment for study population, age and BMI did not materially change these results, although statistical significance was lost after adjustment for serum insulin.

CONCLUSIONS: An inverse association between DNL and SHBG may explain the decreased SHBG levels that are observed in obesity, at least in women.

PMID:33715205 | DOI:10.1111/cen.14459

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An audit to identify adherence of laparoscopic appendicectomy operation notes to Royal College of Surgeons Good Surgical Practice standards

Ir J Med Sci. 2021 Mar 13. doi: 10.1007/s11845-021-02567-6. Online ahead of print.

ABSTRACT

BACKGROUND: Appendicitis is the most common abdominal emergency in England accounting for 40,000 admissions per year. The Good Surgical Practice guideline by Royal College of Surgeons England (RCSEng) defines criteria detailing what constitutes a safe and comprehensive operation note. High-quality operation notes enable continuity of care and safe post-operative management.

AIMS: (1) Assess whether laparoscopic appendicectomy operation notes are adherent to RCSEng criteria. (2) Implement an operation note proforma to improve adherence. (3) Re-audit to assess effectiveness of operation note proforma.

METHODS: A retrospective audit was performed measuring compliance of laparoscopic appendicectomy notes to RCSEng criteria over a 4-month period at a central London tertiary care centre. A laparoscopic appendicectomy operation note proforma was designed and implemented. Compliance to RCSEng criteria was then re-audited against RCSEng criteria, and statistical analysis performed to assess the significance of changes to compliance.

RESULTS: The average compliance with the RCSEng guidelines after the first cycle retrospectively was 56.1%. The average compliance after implementation of the proforma was 98.2%, with above 80% of operation notes satisfying all RSCEng criteria. This was a significant 42.1% (p < 0.0001) increase in average compliance. The implementation of the proforma reduced the amount of hand-written information, saving time and improving legibility of the operation notes.

CONCLUSION: The implementation of an operation note proforma has the ability to significantly improve operation note quality. This simple and effective intervention to improve operation note quality has the potential to improve post-operative safety and continuity of care post laparoscopic appendicectomy.

PMID:33715070 | DOI:10.1007/s11845-021-02567-6

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Boron Nano-hydroxyapatite Composite Increases the Bone Regeneration of Ovariectomized Rabbit Femurs

Biol Trace Elem Res. 2021 Mar 14. doi: 10.1007/s12011-021-02626-0. Online ahead of print.

ABSTRACT

Osteoporosis is a systemic metabolic disease defined by a decreased bone mineral density, microarchitectural deterioration, and an increased incidence of fragility fractures that may lead to morbidity and mortality. Boron may stimulate new bone formation and regeneration, when combined with nano-hydroxyapatite. We questioned whether injecting boron-containing nano-hydroxyapatite composites with hyaluronan increased the bone mineral density and new bone formation in osteoporotic rabbit femurs. The regenerative effects of injectable boron-containing nano-hydroxyapatite composites from 6 to 12 weeks, which may prevent osteoporotic femoral fractures, were assessed. Boron-containing (10 μg/ml) nano-hydroxyapatite composites were injected into the intramedullary femoral cavity with hyaluronan. These significantly increased the histomorphometric new bone surface to the total bone surface ratio at 6 and 9 weeks. The micro-tomographic bone volume to the total volume ratio and bone mineral density in osteoporotic rabbit femurs increased when compared to the hyaluronan (p = 0.004, p = 0.004, p = 0.004, p = 0.01, respectively) and the sham-control (p = 0.01, p = 0.004, p = 0.01, p = 0.037, respectively) groups. The boron-containing group had a higher bone mineralization and new bone formation compared to the nano-hydroxyapatite group, although the difference was not statistically significant. These findings reveal that intramedullary injection of boron-containing nano-hydroxyapatite with hyaluronan increases new bone formation and mineralization in ovariectomized rabbit femurs. Boron-containing nano-hydroxyapatite composites are promising tissue engineering biomaterials that may have regenerative potential in preventing primary and/or secondary femoral fractures in osteoporosis patients.

PMID:33715074 | DOI:10.1007/s12011-021-02626-0

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Dual-energy CT quantification of fractional extracellular space in cirrhotic patients: comparison between early and delayed equilibrium phases and correlation with oesophageal varices

Radiol Med. 2021 Mar 14. doi: 10.1007/s11547-021-01341-z. Online ahead of print.

ABSTRACT

OBJECTIVE: Fractional extracellular space has been validated as a marker of hepatic fibrotic in cirrhotic patients at CT-scan as well as on dual-energy CT, which takes advantage from iodine uptake. Since no consensus still exists between equilibrium phases performed at 3 or 10 min, the first aim of this work is to evaluate performances at the two different time points. Moreover, correlation between fractional extracellular space and oesophageal varices, directly related to liver fibrosis, has been assessed.

MATERIALS AND METHODS: Dual-Energy equilibrium phases at 3 and 10 min were performed within a follow-up CT-protocol scan in cirrhotic patients. Oesophageal varices were endoscopically assessed according to their size. At the two different time points, correlation between iodine density of the right and left liver lobes and correlation between the fractional extracellular space values were assessed. Correlation between fractional extracellular space and endoscopic grade of oesophageal varices was calculated.

RESULTS: No statistical differences were found between the iodine density values from the two liver lobes at the two time points (p = 0.8 at 3′; p = 0.5 at 10′). No statistical difference about fractional extracellular space estimation was found between the two time points (p = 0.17). Correlation between fractional extracellular space values and oesophageal varices was moderate (ρ = 0.45, IC 0.08-0.71, p < 0.05).

CONCLUSION: Fractional extracellular space assessed on dual-energy CT at equilibrium phases with different timing was substantially similar. The moderate correlation found between fractional extracellular space and endoscopic grade of oesophageal varices confirms that CT-scan is not currently reliable as endoscopy.

PMID:33715036 | DOI:10.1007/s11547-021-01341-z

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Three-dimensional volumetric changes of 5 different bone grafts in human maxillary sinuses reconstruction: a randomized clinical study

Oral Maxillofac Surg. 2021 Mar 13. doi: 10.1007/s10006-021-00940-4. Online ahead of print.

ABSTRACT

PURPOSE: This study aimed to compare the three-dimensional volumetric changes of human maxillary sinuses after reconstruction using 5 different bone grafts.

PATIENTS AND METHODS: Patients underwent unilateral maxillary sinus bone height reconstruction using 5 bone substitutes allocated in different groups as follows: group 1 was grafted with autogenous bone graft alone; group 2 with beta-tricalcium phosphate (β-TCP); group 3 with β-TCP + autogenous bone graft 1:1; group 4 with bioactive glass; and group 5 with bioactive glass + autogenous bone graft 1:1. The patients were submitted to cone beam computed tomography in two periods: 15 days after the surgical procedure (T1) and after 6 months (T2). The results were evaluated as the formula T2-T1 expressing the three-volumetric changes of the biomaterials in elapsed time.

RESULTS: The resorption rate of autogenous bone graft was -630.699 ± 300.9 mm3; in the β-TCP group, it was -315.772 ± 125.6 mm3; in the group with β-TCP + autogenous bone graft 1:1, it was -336.205 ± 195.7 mm3; and in groups with bioactive glass and with the addition of autogenous bone graft 1:1, it was -428.878 ± 311.6 mm3 and -576.917 ± 471.6 mm3, respectively, without statistical difference (p = 0.167). Pearson’s correlated test revealed a strong correlation as well as a progressive resorption of the grafts during bone healing.

CONCLUSION: The similar outcomes for the three-dimensional volumetric changes using the bone substitutes evaluated after 6 months of bone healing suggest that all these grafts can be performed to maxillary sinus reconstruction.

PMID:33715054 | DOI:10.1007/s10006-021-00940-4

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Nevin Manimala Statistics

The influence of distinct techniques of local dental anesthesia in 9- to 12-year-old children: randomized clinical trial on pain and anxiety

Clin Oral Investig. 2021 Mar 14. doi: 10.1007/s00784-020-03713-7. Online ahead of print.

ABSTRACT

OBJECTIVES: To evaluate pain, disruptive behavior, and anxiety in children undergoing different local dental anesthetic techniques.

METHODS: This randomized/parallel clinical trial analyzed three groups of patients (9-12 years old) (n = 35) who received infiltrative anesthesia using conventional (CA), vibrational (VBA), and computer-controlled techniques (CCLAD). The outcomes were pain self-perception (Wong-Baker Faces Pain Rating Scale (WBF); Numerical Ranting Scale (NRS)), disruptive behavior (Face, Legg, Activity, Crying, Consolability Scale (FLACC)), anxiety (Corah’s Dental Anxiety Scale; modified Venham Picture test (VPTm)), and physiological parameters (systolic (SBP)/diastolic pressure (DBP); heart rate (HR); oxygen saturation (SpO2); respiratory rate (RR)). Statistical analysis was accomplished using Kruskall-Wallis test and ANOVA for repeated measures (α = 0.05).

RESULTS: Dental anxiety levels at the baseline were similar for all patients. CA promoted less pain than VBA in WBF (p = 0.018) and NRS (p = 0.006) and CCLAD in WBF (p = 0.029). There were no differences in disruptive behavior (FLACC p = 0.573), anxiety (VPTm p = 0.474), blood pressure (SBP p = 0.954; DBP p = 0.899), heart rate (p = 0.726), oxygen saturation (p = 0.477), and respiratory rate (p = 0.930) between anesthetic techniques.

CONCLUSION: Conventional technique resulted in less pain perception for dental local anesthesia.

CLINICAL RELEVANCE: Conventional technique reduces the self-reported pain in children 9-12 years old, and therefore, the use of additional devices or different anesthetic techniques is not justified.

PMID:33715064 | DOI:10.1007/s00784-020-03713-7

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A prognostic score for non-small cell lung cancer resected after neoadjuvant therapy in comparison with the tumor-node-metastases classification and major pathological response

Mod Pathol. 2021 Mar 13. doi: 10.1038/s41379-021-00777-y. Online ahead of print.

ABSTRACT

Studies validating the prognostic accuracy of the tumor-node-metastases (TNM) classification in patients with lung cancer treated by neoadjuvant therapy are scarce. Tumor regression, particularly major pathological response (MPR), is an acknowledged prognostic factor in this setting. We aimed to validate a novel combined prognostic score. This retrospective single-center study was conducted on 117 consecutive patients with non-small cell lung cancer resected after neoadjuvant treatment at a Swiss University Cancer Center between 2000 and 2016. All cases were clinicopathologically re-evaluated. We assessed the prognostic performance of a novel prognostic score (PRSC) combining T-category, lymph node status, and MPR, in comparison with the eighth edition of the TNM classification (TNM8), the size adapted TNM8 as proposed by the International Association for the Study of Lung Cancer (IASLC) and MPR alone. The isolated ypT-category and the combined TNM8 stages accurately differentiated overall survival (OS, stage p = 0.004) and disease-free survival (DFS, stage p = 0.018). Tumor regression had a prognostic impact. Optimal cut-offs for MPR emerged as 65% for adenocarcinoma and 10% for non-adenocarcinoma and were statistically significant for survival (OS p = 0.006, DFS p < 0.001). The PRSC differentiated between three prognostic groups (OS and DFS p < 0.001), and was superior compared to the stratification using MPR alone or the TNM8 systems, visualized by lower Akaike (AIC) and Bayesian information criterion (BIC) values. In the multivariate analyses, stage III tumors (HR 4.956, p = 0.003), tumors without MPR (HR 2.432, p = 0.015), and PRSC high-risk tumors (HR 5.692, p < 0.001) had significantly increased risks of occurring death. In conclusion, we support 65% as the optimal cut-off for MPR in adenocarcinomas. TNM8 and MPR were comparable regarding their prognostic significance. The novel prognostic score performed distinctly better regarding OS and DFS.

PMID:33714982 | DOI:10.1038/s41379-021-00777-y

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Temporal kinetics of bovine mammary IgG secretion into colostrum and transition milk

J Anim Sci. 2021 Mar 14:skab083. doi: 10.1093/jas/skab083. Online ahead of print.

ABSTRACT

Neonatal calf survival and health is predominantly dependent on sufficient consumption of immunoglobulin G (IgG) and the resulting transfer of passive immunity (TPI). In this study we investigate the potential for continued IgG secretion and temporal kinetics of mammary IgG output in sequential milkings performed at 0, 4, 16, 28, 40 and 52 hours post-calving in Holstein dairy cows. For colostrum (0 hour), we also scrutinize the relationships between IgG concentration, volume, refractometer readings (˚Bx values, Brix ®) and concentration of sugars (lactose and glucose). Mammary transcripts postpartum (0 hour) indicated that active IgG secretion continues beyond the first milking (colostrum; n=4-5). IgG measurements at the different timepoints indicated that colostrum represents only 25.1% of the total IgG produced across the six sequential milking timepoints, with a substantial 48.9% being secreted into transition milk over the next three timepoints (4-, 6- and 28-hour) combined. The differences on the basis of IgG concentrations across 0-, 4- and 16-hour milking timepoints were not statistically significant (p=0.1522; n=9). For colostrum, volume remained highly variable, even with induced let-down prior to milking (n=27). Nonetheless, colostrum IgG secretion was significantly co-regulated with volume (R 2=0.915; p<0.001; n=18), an association that was stronger than that measured for lactose (R 2=0.803; p<0.001; n=18) and glucose (R 2=0.467; p=0.002; n=17). Comparing colostrum ˚Bx values to absolute IgG concentrations showed no correlation (R 2=0.127; p=0.07; n=27); biochemical separation of colostrum components indicated that both proteins and non-protein solutes could affect ˚Bx values (p<0.0001 for both; n=5). This suggests that ˚Bx values do not reasonably indicate IgG concentration to serve as a measure of “colostrum quality.” Additionally, our finding that early transition milk (4-, 6- and 28-hour) can contribute substantially more IgG than colostrum forces a rethink of existing feeding paradigms and means to maximize TPI in calves. Collectively, our results reveal the remarkable value of early transition milk and caveats to colostrum assessments that could advance application in enhancing neonatal calf health.

PMID:33715013 | DOI:10.1093/jas/skab083

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High dimensional profiling identifies specific immune types along the recovery trajectories of critically ill COVID19 patients

Cell Mol Life Sci. 2021 Mar 13. doi: 10.1007/s00018-021-03808-8. Online ahead of print.

ABSTRACT

The COVID-19 pandemic poses a major burden on healthcare and economic systems across the globe. Even though a majority of the population develops only minor symptoms upon SARS-CoV-2 infection, a significant number are hospitalized at intensive care units (ICU) requiring critical care. While insights into the early stages of the disease are rapidly expanding, the dynamic immunological processes occurring in critically ill patients throughout their recovery at ICU are far less understood. Here, we have analysed whole blood samples serially collected from 40 surviving COVID-19 patients throughout their recovery in ICU using high-dimensional cytometry by time-of-flight (CyTOF) and cytokine multiplexing. Based on the neutrophil-to-lymphocyte ratio (NLR), we defined four sequential immunotypes during recovery that correlated to various clinical parameters, including the level of respiratory support at concomitant sampling times. We identified classical monocytes as the first immune cell type to recover by restoration of HLA-DR-positivity and the reduction of immunosuppressive CD163 + monocytes, followed by the recovery of CD8 + and CD4 + T cell and non-classical monocyte populations. The identified immunotypes also correlated to aberrant cytokine and acute-phase reactant levels. Finally, integrative analysis of cytokines and immune cell profiles showed a shift from an initially dysregulated immune response to a more coordinated immunogenic interplay, highlighting the importance of longitudinal sampling to understand the pathophysiology underlying recovery from severe COVID-19.

PMID:33715015 | DOI:10.1007/s00018-021-03808-8