Blood Endotoxin Levels as Biomarker of Nonalcoholic Fatty Liver Disease: A Systematic Review and Meta-analysis.

BACKGROUND & AIMS: Growing evidence supports a role of gut-derived metabolites in nonalcoholic fatty liver disease (NAFLD), but the relation of endotoxin levels with gut permeability and NAFLD stage remains unclear. This systematic review with meta-analysis aims to provide further insights. METHODS: PubMed, Embase, and Cochrane Library were searched for studies published until January 2022 assessing blood endotoxins in patients with NAFLD. Meta-analyses and univariate/multivariate meta-regression, as well as correlation analyses, were performed for endotoxin values and potential relationships to disease stage, age, sex, parameters of systemic inflammation, and metabolic syndrome, as well as liver function and histology. RESULTS: Forty-three studies were included, of which 34 were used for meta-analyses. Blood endotoxin levels were higher in patients with simple steatosis vs liver-healthy controls (standardized mean difference, 0.86; 95% confidence interval, 0.62-1.11) as well as in patients with nonalcoholic steatohepatitis vs patients with nonalcoholic fatty liver/non-nonalcoholic steatohepatitis (standardized mean difference, 0.81; 95% confidence interval, 0.27-1.35; P = .0078). Consistently, higher endotoxin levels were observed in patients with more advanced histopathological gradings of liver steatosis and fibrosis. An increase of blood endotoxin levels was partially attributed to a body mass index rise in patients with NAFLD compared with controls. Nevertheless, significant increases of blood endotoxin levels in NAFLD retained after compensation for differences in body mass index, metabolic condition, or liver enzymes. Increases in blood endotoxin levels were associated with increases in C-reactive protein concentrations, and in most cases, paralleled a rise in markers for intestinal permeability. CONCLUSION: Our results support blood endotoxin levels as relevant diagnostic biomarker for NAFLD, both for disease detection as well as staging during disease progression, and might serve as surrogate marker of enhanced intestinal permeability in NAFLD. Registration number in Prospero: CRD42022311166.

Facial thermal response to non-painful stressor in premature and term neonates.

BACKGROUND: This study is a preliminary clinical investigation with the objective to evaluate the facial thermal response of premature and term neonates to a non-painful stressor (hunger) using infrared thermography (IRT). The development of objective and reliable parameters to monitor pain and stress is of relevance for optimal neonatal outcome and achieving a better management of patient comfort. METHODS: We enrolled 12 neonates ranging from 27 to 39 weeks gestation (median: 34) and aged 3-79 days (median: 13). Recordings were performed before and after feeding, with and without hunger. Six regions of interest were chosen for evaluation (nose tip, periorbital and corrugator region, forehead, perioral and chin region). RESULTS: There was an increase in the facial temperature in infants immediately prior to their next feed relative to infants who were not hungry, with the nasal tip being the facial evaluation site with the greatest temperature change. CONCLUSIONS: The IRT appears to be a feasible and suitable method to detect changes in the neonatal patient. The thermal variations observed seem to reflect an arousal mediated by the parasympathetic nervous system, which has been described in existing infant stress research. IMPACT: This is the first study to examine the use of infrared thermography (IRT) in monitoring the facial thermal response to a mild stressor (hunger) in premature and term neonates. Hunger as a mild, non-pain-associated stressor showed a significant effect on the facial temperature. The thermal signature of the regions of interest chosen showed hunger-related thermal variations. Results suggest the feasibility and suitability of IRT as an objective diagnostic tool to approach stress and changes in the condition of the neonatal patient.

Detection of acute ventilatory problems via magnetic induction in a newborn animal model.

BACKGROUND: Magnetic induction measurement (MIM) is a noninvasive method for the contactless registration of respiration in newborn piglets by using measurement coils positioned at the bottom of an incubator. Acute pulmonary problems may be determinants of poor neurological and psychomotor outcomes in preterm infants. The current study tested the detection of pulmonary ventilation disorders via MIM in 11 newborn piglets. METHODS: Six measurement coils determined changes in magnetic induction, depending on the ventilation of the lung, in comparison with flow resistance. Contactless registration of induced acute pulmonary ventilation disorders (apnea, atelectasis, pneumothorax, and aspiration) was detected by MIM. RESULTS: All pathologies except aspiration were detected by MIM. Significant changes occurred after induction of apnea (three coils), malposition of the tube (one coil), and pneumothorax (three coils) (p ≤ 0.05). No significant changes occurred after induction of aspiration (p = 0.12). CONCLUSIONS: MIM seems to have some potential to detect acute ventilation disorders in newborn piglets. The location of the measurement coil related to the animal's position plays a critical role in this process. In addition to an early detection of acute pulmonary problems, potential information pointing to a therapeutic intervention, for example, inhalations or medical respiratory analepsis, may be conceivable with MIM in the future. IMPACT: MIM seems to be a method in which noncontact ventilation disorders of premature and mature infants can be detected. This study is an extension of the experimental setup to obtain preliminary evidence for detection of respiratory activity in neonatal piglets. For the first time, MIM is used to register acute ventilation problems of neonates. The possibility of an early detection of acute ventilation problems via MIM may provide an opportunity to receive patient-side information for therapeutical interventions like inhalations or medical respiratory analepsis.

Influence of Clinical Expertise Between Clinician-Instructors Versus Student-Instructors on the Effectiveness of Ultrasound Courses.

PURPOSE: To investigate how the extent of an ultrasound instructor's clinical expertise influences the level of hands-on ultrasound competency achieved by clinicians after three-day ultrasound courses in abdominal and emergency ultrasound. The second goal was to determine how physicians in residency rate the sonographic and didactic skills of student instructors compared to medical staff instructors. METHOD: A total of N = 100 residents participating in a 3-day ultrasound workshop were randomly trained either by 15 student instructors or by clinical staff physicians, both with > 2 years of teaching experience. Both instructor groups had previously completed 120 hours of didactic instructor training. Ultrasound competencies were assessed by a standardized objective structured clinical examination (OSCE) of healthy individuals. The sonographic and didactic skills of both instructor groups were rated by questionnaires with six-step Likert items (1 = excellent, 6 = poor). RESULTS: The cohort, trained by student instructors, achieved the same scoring level as the second cohort, trained by physician instructors (mean score 76.4, versus 73.7 of max. 100 points, p = 0.28) in the final OSCE. The sonographic qualification was rated for student educators as 1.44 (mean) [1.1-1.62], versus residents 1.46 [1.26-1.61], versus attendings 1.29 [1.05-1.61]. Didactic skill levels were rated without significant differences with means of 1.53, 1.57 and 1.53, respectively. DISCUSSION & CONCLUSION: The didactic competence of student instructors does not differ statistically from the competency levels of experienced physicians. In terms of the acquired ultrasound skills of trainees, our data indicate that student instructors can be as efficient as staff instructors. Therefore, student instructors can be employed as resource-saving ultrasound educators without decreasing the skills level achieved by course participants, provided that they previously underwent a comprehensive didactic and sonographic training program.

A roadmap to using randomization in clinical trials.

BACKGROUND: Randomization is the foundation of any clinical trial involving treatment comparison. It helps mitigate selection bias, promotes similarity of treatment groups with respect to important known and unknown confounders, and contributes to the validity of statistical tests. Various restricted randomization procedures with different probabilistic structures and different statistical properties are available. The goal of this paper is to present a systematic roadmap for the choice and application of a restricted randomization procedure in a clinical trial. METHODS: We survey available restricted randomization procedures for sequential allocation of subjects in a randomized, comparative, parallel group clinical trial with equal (1:1) allocation. We explore statistical properties of these procedures, including balance/randomness tradeoff, type I error rate and power. We perform head-to-head comparisons of different procedures through simulation under various experimental scenarios, including cases when common model assumptions are violated. We also provide some real-life clinical trial examples to illustrate the thinking process for selecting a randomization procedure for implementation in practice. RESULTS: Restricted randomization procedures targeting 1:1 allocation vary in the degree of balance/randomness they induce, and more importantly, they vary in terms of validity and efficiency of statistical inference when common model assumptions are violated (e.g. when outcomes are affected by a linear time trend; measurement error distribution is misspecified; or selection bias is introduced in the experiment). Some procedures are more robust than others. Covariate-adjusted analysis may be essential to ensure validity of the results. Special considerations are required when selecting a randomization procedure for a clinical trial with very small sample size. CONCLUSIONS: The choice of randomization design, data analytic technique (parametric or nonparametric), and analysis strategy (randomization-based or population model-based) are all very important considerations. Randomization-based tests are robust and valid alternatives to likelihood-based tests and should be considered more frequently by clinical investigators.

Ivabradine as adjuvant treatment for chronic heart failure.

BACKGROUND: Chronic heart failure is one of the most common medical conditions, affecting more than 23 million people worldwide. Despite established guideline-based, multidrug pharmacotherapy, chronic heart failure is still the cause of frequent hospitalisation, and about 50% die within five years of diagnosis. OBJECTIVES: To assess the effectiveness and safety of ivabradine in individuals with chronic heart failure. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, and CPCI-S Web of Science in March 2020. We also searched ClinicalTrials.gov and the WHO ICTRP. We checked reference lists of included studies. We did not apply any time or language restrictions. SELECTION CRITERIA: We included randomised controlled trials in which adult participants diagnosed with chronic heart failure were randomly assigned to receive either ivabradine or placebo/usual care/no treatment. We distinguished between type of heart failure (heart failure with a reduced ejection fraction or heart failure with a preserved ejection fraction) as well as between duration of ivabradine treatment (short term (< 6 months) or long term (≥ 6 months)). DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trials for inclusion, extracted data, and checked data for accuracy. We calculated risk ratios (RR) using a random-effects model. We completed a comprehensive 'Risk of bias' assessment for all studies. We contacted authors for missing data. Our primary endpoints were: mortality from cardiovascular causes; quality of life; time to first hospitalisation for heart failure during follow-up; and number of days spent in hospital due to heart failure during follow-up. Our secondary endpoints were: rate of serious adverse events; exercise capacity; and economic costs (narrative report). We assessed the certainty of the evidence applying the GRADE methodology. MAIN RESULTS: We included 19 studies (76 reports) involving a total of 19,628 participants (mean age 60.76 years, 69% male). However, few studies contributed data to meta-analyses due to inconsistency in trial design (type of heart failure) and outcome reporting and measurement. In general, risk of bias varied from low to high across the included studies, with insufficient detail provided to inform judgement in several cases. We were able to perform two meta-analyses focusing on participants with heart failure with a reduced ejection fraction (HFrEF) and long-term ivabradine treatment. There was evidence of no difference between ivabradine and placebo/usual care/no treatment for mortality from cardiovascular causes (RR 0.99, 95% confidence interval (CI) 0.88 to 1.11; 3 studies; 17,676 participants; I2 = 33%; moderate-certainty evidence). Furthermore, we found evidence of no difference in rate of serious adverse events amongst HFrEF participants randomised to receive long-term ivabradine compared with those randomised to placebo, usual care, or no treatment (RR 0.96, 95% CI 0.92 to 1.00; 2 studies; 17,399 participants; I2 = 12%; moderate-certainty evidence). We were not able to perform meta-analysis for all other outcomes, and have low confidence in the findings based on the individual studies. AUTHORS' CONCLUSIONS: We found evidence of no difference in cardiovascular mortality and serious adverse events between long-term treatment with ivabradine and placebo/usual care/no treatment in participants with heart failure with HFrEF. Nevertheless, due to indirectness (male predominance), the certainty of the available evidence is rated as moderate.

Predicting primary stability of orthodontic mini-implants, according to position, screw-size, and bone quality, in the maxilla of aged patients: a cadaveric study.

This study aimed to evaluate the effect of implant size and bone condition on primary stability of orthodontic mini-implants with a view to predict the primary stability before insertion. Four-hundred and forty mini-implants of two different diameters (2.0 and 2.3 mm) and lengths (7 and 12 mm) were inserted at 11 different positions in human cadaver maxillae. Before placement of mini-implants, cone beam computed tomography (CBCT) scans were performed to measure bone density and cortical thickness and, after mini-implant placement, implant stability quotient (ISQ) values were determined by resonance frequency analysis and cofactors were analyzed to determine their influence on the primary stability. Additionally, an equation was developed to predict the expected stability based on implant size and bone quality. Bone density varied between 433 (SD 122) and 587 (SD 249) Hounsfield units (HU), and cortical thickness varied between 0.49 (SD 0.42) and 0.98 (SD 0.60) mm. The lowest ISQ value, of 15.50 (SD 7.29) (bone density: 531 (SD 219) HU; cortical thickness: 0.65 (SD 0.58) mm), was found for a mini-implant of 2.0 × 7 mm and the highest ISQ value, of 46.30 (SD 8.69) (bone density: 587 (SD 249) HU; cortical thickness: 0.98 (SD 0.60) mm), was found for a mini-implant of 2.3 × 11 mm. Statistically significant influences of the cofactors on primary stability were demonstrated. To visualize the predictive power of the model, the observed values versus the predicted values of primary stability were compared and the model fit was represented by residual plots. The expected primary stability can be estimated by a linear regression model comprising the radiologically determined bone density, cortical thickness, implant length and diameter, and placement position.

Observations below multiple lower limits of quantification: How to estimate the mean and variance.

Multiple lower limits of quantification (MLOQs) result if various laboratories are involved in the analysis of concentration data and some observations are too low to be quantified. For normally distributed data under MLOQs there exists only the multiple regression method of Helsel to estimate the mean and variance. We propose a simple imputation method and two new maximum likelihood estimation methods: the multiple truncated sample method and the multiple censored sample method. A simulation study is conducted to compare the performances of the newly introduced methods to Helsel's via the criteria root mean squared error (RMSE) and bias of the parameter estimates. Two and four lower limits of quantification (LLOQs), various amounts of unquantifiable observations and two sample sizes are studied. Furthermore, the robustness is investigated under model misspecification. The methods perform with decreasing accuracy for increasing rates of unquantified observations. Increasing sample sizes lead to smaller bias. There is almost no change in the performance between two and four LLOQs. The magnitude of the variance impairs the performance of all methods. For a smaller variance, the multiple censored sample method leads to superior estimates regarding the RMSE and bias, whereas Helsel's method is superior regarding the bias for a larger variance. Under model misspecification, Helsel's method was inferior to the other methods. Estimating the mean, the multiple censored sample method performed better, whereas the multiple truncated sample method performs best in estimating the variance. Summarizing, for a large sample size and normally distributed data we recommend to use Helsel's method. Otherwise, the multiple censored sample method should be used to obtain estimates of the mean and variance of data including MLOQs.

Impact of Hippotherapy on Gross Motor Function and Quality of Life in Children with Bilateral Cerebral Palsy: A Randomized Open-Label Crossover Study.

This study investigated the effect of hippotherapy on gross motor function (Gross Motor Function Measure [GMFM]-66, GMFM dimension E and D) and quality of life (Child Health Questionnaire [CHQ 28], KIDSCREEN-27 parental versions) in children with bilateral spastic cerebral palsy. Seventy-three children (age: 9.1 ± 3.3 years; male = 44; GMFCS levels II = 27; III = 17; IV = 29) were randomized to an early (n = 35) or late (n = 38) treatment group. Data from 66 probands were available for further analysis. Probands received hippotherapy once to twice weekly during a period of 16 to 20 weeks (mean: 17 treatments) in a crossover approach. Whereas no significant changes were found for total GMFM scores and quality of life parameters, a significant increase in GMFM dimension E was found. Children terminating the study early showed lower mean psychosocial quality of life scores than children who completed the whole study (CHQ-28 "psychosocial dimension"; KIDSCREEN-27 "mood and emotional dimension"). Our data are in line with previous reports and suggest that hippotherapy shows distinct therapeutic strengths with regard to promoting upright stand and gait in children with cerebral palsy. Children with higher psychosocial burden of disease may need special support to get access to and benefit from intensified physiotherapy programs.

Assessing the impact of selection bias on test decisions in trials with a time-to-event outcome.

If past treatment assignments are unmasked, selection bias may arise even in randomized controlled trials. The impact of such bias can be measured by considering the type I error probability. In case of a normally distributed outcome, there already exists a model accounting for selection bias that permits calculating the corresponding type I error probabilities. To model selection bias for trials with a time-to-event outcome, we introduce a new biasing policy for exponentially distributed data. Using this biasing policy, we derive an exact formula to compute type I error probabilities whenever an F-test is performed and no observations are censored. Two exemplary settings, with and without random censoring, are considered in order to illustrate how our results can be applied to compare distinct randomization procedures with respect to their performance in the presence of selection bias. © 2017 The Authors. Statistics in Medicine Published by John Wiley & Sons Ltd.

ERDO - a framework to select an appropriate randomization procedure for clinical trials.

BACKGROUND: Randomization is considered to be a key feature to protect against bias in randomized clinical trials. Randomization induces comparability with respect to known and unknown covariates, mitigates selection bias, and provides a basis for inference. Although various randomization procedures have been proposed, no single procedure performs uniformly best. In the design phase of a clinical trial, the scientist has to decide which randomization procedure to use, taking into account the practical setting of the trial with respect to the potential of bias. Less emphasis has been placed on this important design decision than on analysis, and less support has been available to guide the scientist in making this decision. METHODS: We propose a framework that weights the properties of the randomization procedure with respect to practical needs of the research question to be answered by the clinical trial. In particular, the framework assesses the impact of chronological and selection bias on the probability of a type I error. The framework is applied to a case study with a 2-arm parallel group, single center randomized clinical trial with continuous endpoint, with no-interim analysis, 1:1 allocation and no adaptation in the randomization process. RESULTS: In so doing, we derive scientific arguments for the selection of an appropriate randomization procedure and develop a template which is illustrated in parallel by a case study. Possible extensions are discussed. CONCLUSION: The proposed ERDO framework guides the investigator through a template for the choice of a randomization procedure, and provides easy to use tools for the assessment. The barriers for the thorough reporting and assessment of randomization procedures could be further reduced in the future when regulators and pharmaceutical companies employ similar, standardized frameworks for the choice of a randomization procedure.

MIF promotes B cell chemotaxis through the receptors CXCR4 and CD74 and ZAP-70 signaling.

Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine with chemokine-like functions that plays a pivotal role in the pathogenesis of inflammatory diseases by promoting leukocyte recruitment. We showed that MIF promotes the atherogenic recruitment of monocytes and T cells through its receptors CXCR2 and CXCR4. Effects of MIF on B cell recruitment have not been addressed. In this study, we tested the involvement of MIF in B cell chemotaxis and studied the underlying mechanism. We show that MIF promotes primary murine B cell chemotaxis in a dose-dependent manner, comparable to the B cell chemokines CXCL13 and CXCL12. Splenic B cells express CXCR4 and the receptor CD74 but not CXCR2. Inhibition of CXCR4 or CD74 or a genetic deficiency of Cd74 in primary B cells fully abrogated MIF-mediated B cell migration, implying cooperative involvement of both receptors. MIF stimulation of B cells resulted in a rapid increase in intracellular Ca(2+) mobilization and F-actin polymerization. Intriguingly, the tyrosine kinase ZAP-70 was activated upon MIF and CXCL12 treatment in a CXCR4- and CD74-dependent manner. Pharmacological inhibition of ZAP-70 resulted in abrogation of primary B cell migration. Functional involvement of ZAP-70 was confirmed by small interfering RNA-mediated knockdown in Ramos B cell migration. Finally, primary B cells from ZAP-70 gene-deficient mice exhibited ablated transmigration in response to MIF or CXCL12. We conclude that MIF promotes the migration of B cells through a ZAP-70-dependent pathway mediated by cooperative engagement of CXCR4 and CD74. The data also suggest that MIF may contribute to B cell recruitment in vivo (e.g., in B cell-related immune disorders).

Use of molecular indicators of inflammation to assess the biocompatibility of all-ceramic restorations.

AIM: The purpose of this in vivo study was quantification of inflammatory reaction to ceramic restorations made from lithium disilicate and zirconia by measurement of the concentration of indicators of inflammation in the gingival crevicular fluid (GCF). MATERIAL AND METHODS: Patients out of three prospective cohort-studies investigating three different all-ceramic restoration materials for crowns and fixed dental prostheses were included. Patients needed an associated, unrestored tooth to serve as control. GCF samples were taken from the sulcus of the restored teeth and the related controls (n = 59 pairs) and the concentrations of IL1-beta, IL-1ra and aMMP-8, as indicators of inflammation, were determined by use of ELISA tests. Periodontal status was also assessed clinically by measurement of pocket depth (PD), plaque index (PI) and bleeding on probing (BOP). RESULTS: The concentrations of the inflammation indicators were not significantly different between restored teeth and controls or between lithium disilicate and zirconia restorations (p > 0.05). Furthermore, no significant difference between PD of restored teeth and controls or between groups could be shown. CONCLUSION: Within the limitation of the study, treatment with all-ceramic restorations did not induce inflammatory reactions in a group of periodontal healthy patients. No differences between the gingiva reactions of lithium disilicate and zirconia restorations could be shown.

A systematic review and meta-analysis of removable and fixed implant-supported prostheses in edentulous jaws: post-loading implant loss.

OBJECTIVES: The aim of this systematic review was to analyze post-loading implant loss for implant-supported prostheses in edentulous jaws, regarding a potential impact of implant location (maxilla vs. mandible), implant number per patient, type of prosthesis (removable vs. fixed), and type of attachment system (screw-retained, ball vs. bar vs. telescopic crown). MATERIAL AND METHODS: A systematic literature search for randomized-controlled trials (RCTs) or prospective studies was conducted within PubMed, Cochrane Library, and Embase. Quality assessment of the included studies was carried out, and the review was structured according to PRISMA. Implant loss and corresponding 3- and 5-year survival rates were estimated by means of a Poisson regression model with total exposure time as offset. RESULTS: After title, abstract, and full-text screening, 54 studies were included for qualitative analyses. Estimated 5-year survival rates of implants were 97.9% [95% CI 97.4; 98.4] in the maxilla and 98.9% [95% CI 98.7; 99.1] in the mandible. Corresponding implant loss rates per 100 implant years were significantly higher in the maxilla (0.42 [95% CI 0.33; 0.53] vs. 0.22 [95% CI 0.17; 0.27]; P = 0.0001). Implant loss rates for fixed restorations were significantly lower compared to removable restorations (0.23 [95% CI 0.18; 0.29] vs. 0.35 [95% CI 0.28; 0.44]; P = 0.0148). Four implants and a fixed restoration in the mandible resulted in significantly higher implant loss rates compared to five or more implants with a fixed restoration. The analysis of one implant and a mandibular overdenture also revealed higher implant loss rates than an overdenture on two implants. The same (lower implant number = higher implant loss rate) applied when comparing 2 vs. 4 implants and a mandibular overdenture. Implant loss rates for maxillary overdentures on <4 implants were significantly higher than for four implants (7.22 [95% CI 5.41; 9.64] vs. 2.31 [1.56; 3.42]; P < 0.0001). CONCLUSIONS: Implant location, type of restoration, and implant number do have an influence on the estimated implant loss rate. Consistent reporting of clinical studies is necessary and high-quality studies are needed to confirm the present results.

Estimating the reliability of repeatedly measured endpoints based on linear mixed-effects models. A tutorial.

There are various settings in which researchers are interested in the assessment of the correlation between repeated measurements that are taken within the same subject (i.e., reliability). For example, the same rating scale may be used to assess the symptom severity of the same patients by multiple physicians, or the same outcome may be measured repeatedly over time in the same patients. Reliability can be estimated in various ways, for example, using the classical Pearson correlation or the intra-class correlation in clustered data. However, contemporary data often have a complex structure that goes well beyond the restrictive assumptions that are needed with the more conventional methods to estimate reliability. In the current paper, we propose a general and flexible modeling approach that allows for the derivation of reliability estimates, standard errors, and confidence intervals - appropriately taking hierarchies and covariates in the data into account. Our methodology is developed for continuous outcomes together with covariates of an arbitrary type. The methodology is illustrated in a case study, and a Web Appendix is provided which details the computations using the R package CorrMixed and the SAS software. Copyright © 2016 John Wiley & Sons, Ltd.

Three-Dimensional Evaluation of Implant Bed Preparation and the Influence on Primary Implant Stability After Using 2 Different Surgical Techniques.

PURPOSE: Surgical techniques affect primary implant stability, which is required for osseointegration. The aim of this study was to investigate the influence of full-guided surgery on the dimension of implant site in relation to primary stability. MATERIALS AND METHODS: After implant site preparation in artificial bone by full-guided (FG) or non-guided (NG) workflows to create final diameters of 3.3, 4.1, and 4.8mm and depths of 8 or 12 mm, computed tomograms were obtained and the volume of the osteotomies was analyzed 3 dimensionally. After comparing implant insertions, the implant stability quotient (ISQ) was measured by resonance frequency analysis (RFA). RESULTS: Volume analysis of the implant site showed significant differences (P < .0001) between surgical procedures (FG vs NG) at a depth of 12 mm for all diameters (3.3 mm, 61.98 ± 5.84 vs 80.96 ± 9.65 mm(3); 4.1 mm, 107.45 ± 6.91 vs 132.07 ± 5.16 mm(3); 4.8 mm, 158.62 ± 10.21 vs 182.00 ± 6.25 mm(3)) and at a depth of 8 mm for diameters of 4.1 mm (71.76 ± 8.38 vs 83.64 ± 7.54 mm(3)) and 4.8 mm (103.84 ± 6.73 vs 120.55 ± 14.63 mm(3)). RFA showed significant differences for implants with a diameter of 4.8 mm and lengths of 12 mm (ISQ, 69.3 ± 4.09 for FG vs 65.05 ± 5.61 for NG; P = .0007) and 8 mm (64.5 ± 4.16 for FG vs 58.85 ± 6.72 for NG; P = .0107). CONCLUSIONS: The use of FG implant surgery decreases the bone volume removed during osteotomy preparation, which can lead to greater primary stability.

Three-dimensional evaluation of the different donor sites of the mandible for autologous bone grafts.

OBJECTIVES: For effective placement of endosseous implants, a sufficient volume of bone is required at the recipient site. The aim of this study is to evaluate the density and maximum amount of harvestable bone graft required from the mandible symphysis, coronoid process, and ascending ramus, depending on dentition. MATERIALS AND METHODS: CT data from 42 patients (13 females and 29 males) in DICOM format were read using special planning software. Three different virtual bone grafts were created, and the dimension outcomes, surface, volume, and density were measured in a dentate group (n = 22) and a total edentulous group (n = 20). RESULTS: Comparisons between corresponding bone grafts showed no difference for the symphysis and coronoid process in relation to dentition, and no difference in bone density was observed. However, significant changes between the average values of the ramus were found between the two groups (p < 0.0001). CONCLUSIONS: Appropriate software and CT data can deliver more accurate examinations of the mandible in relation to potential donor sites. Atrophy primarily affects the ascending ramus; the symphysis and coronoid process are only slightly influenced. CLINICAL RELEVANCE: Using appropriate software in conjunction with implant planning, it is possible to analyze potential donor areas within the jaw and create virtual bone grafts.

Is the Maxillary Sinus Really Suitable in Sex Determination? A Three-Dimensional Analysis of Maxillary Sinus Volume and Surface Depending on Sex and Dentition.

The morphometric analysis of maxillary sinus was recently presented as a helpful instrument for sex determination. The aim of the present study was to examine the volume and surface of the fully dentate, partial, and complete edentulous maxillary sinus depending on the sex. Computed tomography data from 276 patients were imported in DICOM format via special virtual planning software, and surfaces (mm) and volumes (mm) of maxillary sinuses were measured. In sex-specific comparisons (women vs men), statistically significant differences for the mean maxillary sinus volume and surface were found between fully dentate (volume, 13,267.77 mm vs 16,623.17 mm, P < 0.0001; surface, 3480.05 mm vs 4100.83 mm, P < 0.0001) and partially edentulous (volume, 10,577.35 mm vs 14,608.10 mm, P = 0.0002; surface, 2980.11 mm vs 3797.42 mm, P < 0.0001) or complete edentulous sinuses (volume, 11,200.99 mm vs 15,382.29 mm, P < 0.0001; surface, 3118.32 mm vs 3877.25 mm, P < 0.0001). For males, the statistically different mean values were calculated between fully dentate and partially edentulous (volume, P = 0.0022; surface, P = 0.0048) maxillary sinuses. Between the sexes, no differences were only measured for female and male partially dentate fully edentulous sinuses (2 teeth missing) and between partially edentulous sinuses in women and men (1 teeth vs 2 teeth missing). With a corresponding software program, it is possible to analyze the maxillary sinus precisely. The dentition influences the volume and surface of the pneumatic maxillary sinus. Therefore, sex determination is possible by analysis of the maxillary sinus event through the increase in pneumatization.

Can in-vitro chemoresponse assays help find new treatment regimens for malignant gliomas?

Various in-vitro chemosensitivity and resistance assays (CSRAs) have been demonstrated to be helpful decision aids for non-neurological tumors. Here, we evaluated the performance characteristics of two CSRAs for glioblastoma (GB) cells. The chemoresponse of fresh GB cells from 30 patients was studied in vitro using the ATP tumor chemoresponse assay and the chemotherapy resistance assay (CTR-Test). Both assay platforms provided comparable results. Of seven different chemotherapeutic drugs and drug combinations tested in vitro, treosulfan plus cytarabine (TARA) was the most effective, followed by nimustine (ACNU) plus teniposide (VM26) and temozolomide (TMZ). Whereas ACNU/VM26 and TMZ have proven their clinical value for malignant gliomas in large randomized studies, TARA has not been successful in newly diagnosed gliomas. This seeming discrepancy between in vitro and clinical result might be explained by the pharmacological behavior of treosulfan. Our results show reasonable agreement between two cell-based CSRAs. They appear to confirm the clinical effectiveness of drugs used in GB treatment as long as pharmacological preconditions such as overcoming the blood-brain barrier are properly considered.