First experience using a novel microsurgical robotic device for free flap surgery in cranio- and maxillofacial surgery.

Many surgical fields profit from robotic support devices. After the first case reports about the use of a special microsurgical roboter (Symani Sugrical System, Medical Microinstruments, Pisa, Italy) we evaluated the potential of such a device in cranio- and maxillofacial surgery in a world's first single-center case series. This novel piece of equipment is meant to assist the surgeon anastomosing small vessels, nerves and lymphatic vessels. In total 30 free flaps were performed and compared to another 30 conventionally anastomosed free flaps. In total 127 anastomoses were surveyed. We encountered a lot of potential for robotic supported operations in the field of cranio- and maxillofacial surgery. However, the surgery time for robotic supported anastomosis with an average time of 32.5 min to perform arterial anastomosis was significant longer than the conventional ones, which needed 11.8 min on average. Tremor Filter and Motion Scaling are promising features for future microsurgery but the grip of the microinstruments has to be improved. It remains to be seen if the potential will be validated after the upcoming learning period and if robotic support devices will prevail in cranio- and maxillofacial surgery.

Spermatogenesis after gonadotoxic childhood treatment: follow-up of 12 patients.

STUDY QUESTION: What is the long-term impact of presumed gonadotoxic treatment during childhood on the patient's testicular function at adulthood? SUMMARY ANSWER: Although most patients showed low testicular volumes and some degree of reproductive hormone disruption 12.3 (2.3-21.0) years after gonadotoxic childhood therapy, active spermatogenesis was demonstrated in the semen sample of 8 out of the 12 patients. WHAT IS KNOWN ALREADY: In recent decades, experimental testicular tissue banking programmes have been set up to safeguard the future fertility of young boys requiring chemo- and/or radiotherapy with significant gonadotoxicity. Although the risk of azoospermia following such therapies is estimated to be high, only limited long-term data are available on the reproductive potential at adulthood. STUDY DESIGN SIZE DURATION: This single-centre prospective cohort study was conducted between September 2020 and February 2023 and involved 12 adult patients. PARTICIPANTS/MATERIALS SETTING METHODS: This study was carried out in a tertiary care centre and included 12 young adults (18.1-28.3 years old) who had been offered testicular tissue banking prior to gonadotoxic treatment during childhood. All patients had a consultation and physical examination with a fertility specialist, a scrotal ultrasound to measure the testicular volumes and evaluate the testicular parenchyma, a blood test for assessment of reproductive hormones, and a semen analysis. MAIN RESULTS AND THE ROLE OF CHANCE: Testicular tissue was banked prior to the gonadotoxic treatment for 10 out of the 12 included patients. Testicular volumes were low for 9 patients, and 10 patients showed some degree of reproductive hormone disruption. Remarkably, ongoing spermatogenesis was demonstrated in 8 patients at a median 12.3 (range 2.3-21.0) years post-treatment. LIMITATIONS REASONS FOR CAUTION: This study had a limited sample size, making additional research with a larger study population necessary to verify these preliminary findings. WIDER IMPLICATIONS OF THE FINDINGS: These findings highlight the need for multicentric research with a larger study population to establish universal inclusion criteria for immature testicular tissue banking. STUDY FUNDING/COMPETING INTERESTS: This study was conducted with financial support from the Research Programme of the Research Foundation-Flanders (G010918N), Kom Op Tegen Kanker, and Scientific Fund Willy Gepts (WFWG19-03). The authors declare no competing interests. TRIAL REGISTRATION NUMBER: NCT04202094; https://clinicaltrials.gov/ct2/show/NCT04202094?id=NCT04202094&draw=2&rank=1 This study was registered on 6 December 2019, and the first patient was enrolled on 8 September 2020.

Scapular free flap as a good choice for mandibular reconstruction: 119 out of 280 cases after resection of oral squamous cell carcinoma in a single institution.

Microsurgical procedures for reconstruction after resection of head and neck tumours have become standardised and reliable. Among them, the scapular free flap is used less often, mostly to avoid excessive operating times. We hypothesise that complex reconstructions after resection of oral squamous cell carcinoma (OSCC) are successful even with time-consuming free flaps such as the scapular free flap. In this retrospective, single-centre study, we used the evaluation of medical records to investigate the postoperative outcome of microvascular reconstruction after ablative surgery of OSCC. Associations among the categorical variables were analysed using Pearson's chi squared test or Fisher's exact test. Among the continuous variables, the t test or Mann-Whitney U test were used as appropriate. For multivariate analysis, the logistic regression model was calculated. In the sample of 280 free flap reconstructions, we performed 142 radial forearm and 119 scapular free flaps. The American Society of Anesthesiology (ASA) score (p=0.006) and the duration of the operation (p=0.010) are independent factors which influence the need for operative revisions. The type of free flap is irrelevant for that. With 4.2% flap losses, scapular free flaps were successful; even in patients ≥ 70 years old (0 flap losses). Complex reconstructions after surgical resection of OSCC are successful even in aged patients. The scapular free flap is a good choice for mandibular reconstruction despite the time-consuming intraoperative repositioning of the patient. In an increasingly ageing group of patients, who have more vascular diseases, scapular free flaps could be a very successful alternative after ablative surgery of oral squamous cell carcinoma.

Sparse relative risk regression models.

Clinical studies where patients are routinely screened for many genomic features are becoming more routine. In principle, this holds the promise of being able to find genomic signatures for a particular disease. In particular, cancer survival is thought to be closely linked to the genomic constitution of the tumor. Discovering such signatures will be useful in the diagnosis of the patient, may be used for treatment decisions and, perhaps, even the development of new treatments. However, genomic data are typically noisy and high-dimensional, not rarely outstripping the number of patients included in the study. Regularized survival models have been proposed to deal with such scenarios. These methods typically induce sparsity by means of a coincidental match of the geometry of the convex likelihood and a (near) non-convex regularizer. The disadvantages of such methods are that they are typically non-invariant to scale changes of the covariates, they struggle with highly correlated covariates, and they have a practical problem of determining the amount of regularization. In this article, we propose an extension of the differential geometric least angle regression method for sparse inference in relative risk regression models. A software implementation of our method is available on github (https://github.com/LuigiAugugliaro/dgcox).

Antibiotic Treatment in the First Week of Life Impacts the Growth Trajectory in the First Year of Life in Term Infants.

OBJECTIVE: Antibiotic treatment in early life appears to increase the risk for childhood overweight and obesity. So far, the association between antibiotics administrated specifically during the first week of life and growth has not been studied. Therefore, we studied the association between growth and antibiotics, given in the first week of life and antibiotic courses later in the first year of life. METHOD: A prospective observational birth cohort of 436 term infants with 151 receiving broad-spectrum antibiotics for suspected neonatal infection (AB+), and 285 healthy controls (AB-) was followed during their first year. Weight, height, and additional antibiotic courses were collected monthly. A generalized-additive-mixed-effects model was used to fit the growth data. Growth curve estimation was controlled for differences in sex, gestational age, delivery mode, exclusive breast-feeding, tobacco exposure, presence of siblings, and additional antibiotic courses. RESULTS: Weight-for-age and length-for-age increase was lower in AB+ compared with AB- (P < 0.0001), resulting in a lower weight and length increase 6.26 kg (standard error [SE] 0.07 kg) and 25.4 cm (SE 0.27 cm) versus 6.47 kg (SE 0.06 kg) and 26.4 cm (SE 0.21 cm) (P < 0.05 and P < 0.005, respectively) in the first year of life. Approximately 30% of the children in both groups received additional antibiotic course(s) in their first year, whereafter additional weight gain of 76 g per course was observed (P = 0.0285). CONCLUSIONS: Decreased growth was observed after antibiotics in the first week of life, whereas increased growth was observed after later antibiotic course(s) in term born infants in the first year of life. Therefore, timing of antibiotics may determine the association with growth.

Robust dose planning objectives for mesorectal radiotherapy of early stage rectal cancer - A multicentre dose planning study.

BACKGROUND AND PURPOSE: Organ preservation strategies are increasingly being explored for early rectal cancer. This requires revision of target volumes according to disease stage, as well as new guidelines for treatment planning. We conducted an international, multicentre dose planning study to develop robust planning objectives for modern radiotherapy of a novel mesorectal-only target volume, as implemented in the STAR-TReC trial (NCT02945566). MATERIALS AND METHODS: The published literature was used to establish relevant dose levels for organ at risk (OAR) plan optimisation. Ten representative patients with early rectal cancer were identified. Treatment scans had mesorectal target volumes as well as bowel cavity, bladder and femoral heads outlined, and were circulated amongst the three participating institutions. Each institution produced plans for short course (SCRT, 5 × 5 Gy) and long course (LCRT, 25 × 2 Gy) treatment, using volumetric modulated arc therapy on different dose planning systems. Optimisation objectives for OARs were established by determining dose metric objectives achievable for ≥90% of plans. RESULTS: Sixty plans, all fulfilling target coverage criteria, were produced. The planning results and literature review suggested optimisation objectives for SCRT: V 10Gy < 180 cm3, V 18Gy < 110 cm3, V 23Gy < 85 cm3 for bowel cavity; V 21Gy < 15% and V 25Gy < 5% for bladder; and V 12.5Gy < 11% for femoral heads. Corresponding objectives for LCRT: V 20Gy < 180 cm3, V 30Gy < 130 cm3, V 45Gy < 90 cm3 for bowel cavity; V 35Gy < 22% and V 50Gy < 7% for bladder; and V 25Gy < 15% for femoral heads. Constraints were validated across all three institutions. CONCLUSION: We utilized a multicentre planning study approach to develop robust planning objectives for mesorectal radiotherapy for early rectal cancer.

De novo construction of polyploid linkage maps using discrete graphical models.

MOTIVATION: Linkage maps are used to identify the location of genes responsible for traits and diseases. New sequencing techniques have created opportunities to substantially increase the density of genetic markers. Such revolutionary advances in technology have given rise to new challenges, such as creating high-density linkage maps. Current multiple testing approaches based on pairwise recombination fractions are underpowered in the high-dimensional setting and do not extend easily to polyploid species. To remedy these issues, we propose to construct linkage maps using graphical models either via a sparse Gaussian copula or a non-paranormal skeptic approach. RESULTS: We determine linkage groups, typically chromosomes, and the order of markers in each linkage group by inferring the conditional independence relationships among large numbers of markers in the genome. Through simulations, we illustrate the utility of our map construction method and compare its performance with other available methods, both when the data are clean and contain no missing observations and when data contain genotyping errors. Our comprehensive map construction method makes full use of the dosage SNP data to reconstruct linkage map for any bi-parental diploid and polyploid species. We apply the proposed method to three genotype datasets: barley, peanut and potato from diploid and polyploid populations. AVAILABILITY AND IMPLEMENTATION: The method is implemented in the R package netgwas which is freely available at https://cran.r-project.org/web/packages/netgwas. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Stability estimation of autoregulated genes under Michaelis-Menten-type kinetics.

Feedback loops are typical motifs appearing in gene regulatory networks. In some well-studied model organisms, including Escherichia coli, autoregulated genes, i.e., genes that activate or repress themselves through their protein products, are the only feedback interactions. For these types of interactions, the Michaelis-Menten (MM) formulation is a suitable and widely used approach, which always leads to stable steady-state solutions representative of homeostatic regulation. However, in many other biological phenomena, such as cell differentiation, cancer progression, and catastrophes in ecosystems, one might expect to observe bistable switchlike dynamics in the case of strong positive autoregulation. To capture this complex behavior we use the generalized family of MM kinetic models. We give a full analysis regarding the stability of autoregulated genes. We show that the autoregulation mechanism has the capability to exhibit diverse cellular dynamics including hysteresis, a typical characteristic of bistable systems, as well as irreversible transitions between bistable states. We also introduce a statistical framework to estimate the kinetics parameters and probability of different stability regimes given observational data. Empirical data for the autoregulated gene SCO3217 in the SOS system in Streptomyces coelicolor are analyzed. The coupling of a statistical framework and the mathematical model can give further insight into understanding the evolutionary mechanisms toward different cell fates in various systems.

MeCP2-regulated miRNAs control early human neurogenesis through differential effects on ERK and AKT signaling.

Rett syndrome (RTT) is an X-linked, neurodevelopmental disorder caused primarily by mutations in the methyl-CpG-binding protein 2 (MECP2) gene, which encodes a multifunctional epigenetic regulator with known links to a wide spectrum of neuropsychiatric disorders. Although postnatal functions of MeCP2 have been thoroughly investigated, its role in prenatal brain development remains poorly understood. Given the well-established importance of microRNAs (miRNAs) in neurogenesis, we employed isogenic human RTT patient-derived induced pluripotent stem cell (iPSC) and MeCP2 short hairpin RNA knockdown approaches to identify novel MeCP2-regulated miRNAs enriched during early human neuronal development. Focusing on the most dysregulated miRNAs, we found miR-199 and miR-214 to be increased during early brain development and to differentially regulate extracellular signal-regulated kinase (ERK)/mitogen-activated protein kinase and protein kinase B (PKB/AKT) signaling. In parallel, we characterized the effects on human neurogenesis and neuronal differentiation brought about by MeCP2 deficiency using both monolayer and three-dimensional (cerebral organoid) patient-derived and MeCP2-deficient neuronal culture models. Inhibiting miR-199 or miR-214 expression in iPSC-derived neural progenitors deficient in MeCP2 restored AKT and ERK activation, respectively, and ameliorated the observed alterations in neuronal differentiation. Moreover, overexpression of miR-199 or miR-214 in the wild-type mouse embryonic brains was sufficient to disturb neurogenesis and neuronal migration in a similar manner to Mecp2 knockdown. Taken together, our data support a novel miRNA-mediated pathway downstream of MeCP2 that influences neurogenesis via interactions with central molecular hubs linked to autism spectrum disorders.

The potential of eHealth in otorhinolaryngology-head and neck surgery: patients' perspectives.

The use of modern information and communication technologies (ICT) in daily life has significantly increased during the last several years. These essential online technologies have also found their way into the healthcare system. The use of modern ICT for health reasons can be summarized by the term 'eHealth'. Despite the potential importance of eHealth in the field of otorhinolaryngology (ORL), there is little understanding of patients' attitudes towards the deeper integration of these technologies into intersectoral care. The aim of this study was to gain a better understanding of patients' attitudes towards the use of modern ICT for intersectoral communication and information transfer in the field of ORL. Therefore, a structured interview was developed by an interdisciplinary team of otorhinolaryngologists, public health researchers, and information technology (IT) specialists. Overall, 211 ORL patients were interviewed at the Department of Otorhinolaryngology-Head and Neck Surgery, Tuebingen University Hospital, Germany, and 203 of these patients completed the interview. This study revealed ORL patients' perspectives on the potential of eHealth, especially for appointment scheduling, appointment reminders, and intersectoral communication of personal medical information. Furthermore, this study provides evidence that data security and the impacts of eHealth on the physician-patient relationship and on treatment quality warrant special attention in future research.

Commissioning Monte Carlo algorithm for robotic radiosurgery using cylindrical 3D-array with variable density inserts.

INTRODUCTION: To commission the Monte Carlo (MC) algorithm based model of CyberKnife robotic stereotactic system (CK) and evaluate the feasibility of patient specific QA using the ArcCHECK cylindrical 3D-array (AC) with Multiplug inserts (MP). RESULTS: Four configurations were used for simple beam setup and two for patient QA, replacing water equivalent inserts by lung. For twelve collimators (5-60mm) in simple setup, mean (SD) differences between MC and RayTracing algorithm (RT) of the number of points failing the 3%/1mmgamma criteria were 1(1), 1(3), 1(2) and 1(2) for the four MP configurations. Tracking fiducials were placed within AC for patient QA. Single lung insert setup resulted in mean gamma-index 2%/2mm of 90.5% (range [74.3-95.9]) and 82.3% ([66.8-94.5]) for MC and RT respectively, while 93.5% ([86.8-98.2]) and 86.2% ([68.7-95.4]) in presence of largest inhomogeneities, showing significant differences (p<0.05). DISCUSSION: After evaluating the potential effects, 1.12g/cc PMMA and 0.09g/cc lung material assignment showed the best results. Overall, MC-based model showed superior results compared to RT for simple and patient specific testing, using a 2%/2mm criteria. Results are comparable with other reported commissionings for flattening filter free (FFF) delivery. Further improvement of MC calculation might be challenging as Multiplan has limited material library. CONCLUSIONS: The AC with Multiplug allowed for comprehensive commissioning of CyberKnife MC algorithm and is useful for patient specific QA for stereotactic body radiation therapy. MC calculation accuracy might be limited due to Multiplan's insufficient material library; still results are comparable with other reported commissioning measurements using FFF beams.

Autonomous Metabolic Oscillations Robustly Gate the Early and Late Cell Cycle.

Eukaryotic cell division is known to be controlled by the cyclin/cyclin dependent kinase (CDK) machinery. However, eukaryotes have evolved prior to CDKs, and cells can divide in the absence of major cyclin/CDK components. We hypothesized that an autonomous metabolic oscillator provides dynamic triggers for cell-cycle initiation and progression. Using microfluidics, cell-cycle reporters, and single-cell metabolite measurements, we found that metabolism of budding yeast is a CDK-independent oscillator that oscillates across different growth conditions, both in synchrony with and also in the absence of the cell cycle. Using environmental perturbations and dynamic single-protein depletion experiments, we found that the metabolic oscillator and the cell cycle form a system of coupled oscillators, with the metabolic oscillator separately gating and maintaining synchrony with the early and late cell cycle. Establishing metabolism as a dynamic component within the cell-cycle network opens new avenues for cell-cycle research and therapeutic interventions for proliferative disorders.

Confidence intervals for intraclass correlation coefficients in variance components models.

Confidence intervals for intraclass correlation coefficients in agreement studies with continuous outcomes are model-specific and no generic approach exists. This paper provides two generic approaches for intraclass correlation coefficients of the form [Formula: see text] The first approach uses Satterthwaite's approximation and an F-distribution. The second approach uses the first and second moments of the intraclass correlation coefficient estimate in combination with a Beta distribution. Both approaches are based on the restricted maximum likelihood estimates for the variance components involved. Simulation studies are conducted to examine the coverage probabilities of the confidence intervals for agreement studies with a mix of small sample sizes. Two different three-way variance components models and balanced and unbalanced one-way random effects models are investigated. The proposed approaches are compared with other approaches developed for these specific models. The approach based on the F-distribution provides acceptable coverage probabilities, but the approach based on the Beta distribution results in accurate coverages for most settings in both balanced and unbalanced designs. A real agreement study is provided to illustrate the approaches.

Implementing meta-analysis from genome-wide association studies for pork quality traits.

Pork quality plays an important role in the meat processing industry. Thus, different methodologies have been implemented to elucidate the genetic architecture of traits affecting meat quality. One of the most common and widely used approaches is to perform genome-wide association (GWA) studies. However, a limitation of many GWA in animal breeding is the limited power due to small sample sizes in animal populations. One alternative is to implement a meta-analysis of GWA (MA-GWA) combining results from independent association studies. The objective of this study was to identify significant genomic regions associated with meat quality traits by performing MA-GWA for 8 different traits in 3 independent pig populations. Results from MA-GWA were used to search for genes possibly associated with the set of evaluated traits. Data from 3 pig data sets (U.S. Meat Animal Research Center, commercial, and Michigan State University Pig Resource Population) were used. A MA was implemented by combining -scores derived for each SNP in every population and then weighting them using the inverse of estimated variance of SNP effects. A search for annotated genes retrieved genes previously reported as candidates for shear force (calpain-1 catalytic subunit [] and calpastatin []), as well as for ultimate pH, purge loss, and cook loss (protein kinase, AMP-activated, γ 3 noncatalytic subunit []). In addition, novel candidate genes were identified for intramuscular fat and cook loss (acyl-CoA synthetase family member 3 mitochondrial []) and for the objective measure of muscle redness, CIE a* (glycogen synthase 1, muscle [] and ferritin, light polypeptide []). Thus, implementation of MA-GWA allowed integration of results for economically relevant traits and identified novel genes to be tested as candidates for meat quality traits in pig populations.

Incidence of Malignancies in Patients With Antineutrophil Cytoplasmic Antibody-Associated Vasculitis Diagnosed Between 1991 and 2013.

OBJECTIVE: To investigate the incidence of malignancies during longitudinal followup of patients with antineutrophil cytoplasmic antibody-associated vasculitis (AAV), and to examine the effect of immunosuppressive therapy on malignancy risk in these patients. METHODS: The study population consisted of patients with histopathologically confirmed AAV, diagnosed between 1991 and 2013 at a large university hospital. The mean duration of followup was 10 years. Malignancy incidence was assessed using the Dutch National Pathology Database. Incidence rates from the Netherlands Cancer Registry were used to compare malignancy incidence in the AAV cohort to that in the general Dutch population. RESULTS: Thirty-six of 138 patients with AAV developed a total of 85 malignancies during a mean followup of 9.7 years. The sex-, age-, and calendar year-adjusted malignancy risk was 2.21-fold higher (95% confidence interval [95% CI] 1.64-2.92) than that in the general population. Non-melanoma skin cancers occurred most frequently (standardized incidence ratio 4.23 [95% CI 2.76-6.19]). The incidence rates of other malignancies were not significantly increased. Malignancy risk was associated with the duration of cyclophosphamide (CYC) therapy and, interestingly, was not increased in patients who had received CYC for <1 year. CONCLUSION: Patients with AAV have a higher risk of malignancy than the general population, but this risk is accounted for solely by non-melanoma skin cancers. Over the years, the risk of other malignancies-specifically bladder and hematologic malignancies-has decreased in patients with AAV. This finding reflects ongoing efforts to reduce CYC exposure by developing new treatment regimens.

γ-H2AX foci as in vivo effect biomarker in children emphasize the importance to minimize x-ray doses in paediatric CT imaging.

OBJECTIVES: Investigation of DNA damage induced by CT x-rays in paediatric patients versus patient dose in a multicentre setting. METHODS: From 51 paediatric patients (median age, 3.8 years) who underwent an abdomen or chest CT examination in one of the five participating radiology departments, blood samples were taken before and shortly after the examination. DNA damage was estimated by scoring γ-H2AX foci in peripheral blood T lymphocytes. Patient-specific organ and tissue doses were calculated with a validated Monte Carlo program. Individual lifetime attributable risks (LAR) for cancer incidence and mortality were estimated according to the BEIR VII risk models. RESULTS: Despite the low CT doses, a median increase of 0.13 γ-H2AX foci/cell was observed. Plotting the induced γ-H2AX foci versus blood dose indicated a low-dose hypersensitivity, supported also by an in vitro dose-response study. Differences in dose levels between radiology centres were reflected in differences in DNA damage. LAR of cancer mortality for the paediatric chest CT and abdomen CT cohort was 0.08 and 0.13 ‰ respectively. CONCLUSION: CT x-rays induce DNA damage in paediatric patients even at low doses and the level of DNA damage is reduced by application of more effective CT dose reduction techniques and paediatric protocols. .

Identification of proteomic biomarkers predicting prostate cancer aggressiveness and lethality despite biopsy-sampling error.

BACKGROUND: Key challenges of biopsy-based determination of prostate cancer aggressiveness include tumour heterogeneity, biopsy-sampling error, and variations in biopsy interpretation. The resulting uncertainty in risk assessment leads to significant overtreatment, with associated costs and morbidity. We developed a performance-based strategy to identify protein biomarkers predictive of prostate cancer aggressiveness and lethality regardless of biopsy-sampling variation. METHODS: Prostatectomy samples from a large patient cohort with long follow-up were blindly assessed by expert pathologists who identified the tissue regions with the highest and lowest Gleason grade from each patient. To simulate biopsy-sampling error, a core from a high- and a low-Gleason area from each patient sample was used to generate a 'high' and a 'low' tumour microarray, respectively. RESULTS: Using a quantitative proteomics approach, we identified from 160 candidates 12 biomarkers that predicted prostate cancer aggressiveness (surgical Gleason and TNM stage) and lethal outcome robustly in both high- and low-Gleason areas. Conversely, a previously reported lethal outcome-predictive marker signature for prostatectomy tissue was unable to perform under circumstances of maximal sampling error. CONCLUSIONS: Our results have important implications for cancer biomarker discovery in general and development of a sampling error-resistant clinical biopsy test for prediction of prostate cancer aggressiveness.

Sex steroids in relation to sexual and skeletal maturation in obese male adolescents.

BACKGROUND: Childhood obesity is associated with an accelerated skeletal maturation. However, data concerning pubertal development and sex steroid levels in obese adolescents are scarce and contrasting. OBJECTIVES: To study sex steroids in relation to sexual and skeletal maturation and to serum prostate specific antigen (PSA), as a marker of androgen activity, in obese boys from early to late adolescence. METHODS: Ninety obese boys (aged 10-19 y) at the start of a residential obesity treatment program and 90 age-matched controls were studied cross-sectionally. Pubertal status was assessed according to the Tanner method. Skeletal age was determined by an x-ray of the left hand. Morning concentrations of total testosterone (TT) and estradiol (E2) were measured by liquid chromatography-tandem mass spectrometry, free T (FT) was measured by equilibrium dialysis, and LH, FSH, SHBG, and PSA were measured by immunoassays. RESULTS: Genital staging was comparable between the obese and nonobese groups, whereas skeletal bone advancement (mean, 1 y) was present in early and midadolescence in the obese males. Although both median SHBG and TT concentrations were significantly (P < .001) lower in obese subjects during mid and late puberty, median FT, LH, FSH, and PSA levels were comparable to those of controls. In contrast, serum E2 concentrations were significantly (P < .001) higher in the obese group at all pubertal stages. CONCLUSION: Obese boys have lower circulating SHBG and TT, but similar FT concentrations during mid and late puberty in parallel with a normal pubertal progression and serum PSA levels. Our data indicate that in obese boys, serum FT concentration is a better marker of androgen activity than TT. On the other hand, skeletal maturation and E2 were increased from the beginning of puberty, suggesting a significant contribution of hyperestrogenemia in the advancement of skeletal maturation in obese boys.

Bone size and bone strength are increased in obese male adolescents.

CONTEXT: Controversy exists on the effect of obesity on bone development during puberty. OBJECTIVE: Our objective was to determine differences in volumetric bone mineral density (vBMD) and bone geometry in male obese adolescents (ObAs) in overlap with changes in bone maturation, muscle mass and force development, and circulating sex steroids and IGF-I. We hypothesized that changes in bone parameters are more evident at the weight-bearing site and that changes in serum estradiol are most prominent. DESIGN, SETTING, AND PARTICIPANTS: We recruited 51 male ObAs (10-19 years) at the entry of a residential weight-loss program and 51 healthy age-matched and 51 bone-age-matched controls. MAIN OUTCOME MEASURES: vBMD and geometric bone parameters, as well as muscle and fat area were studied at the forearm and lower leg by peripheral quantitative computed tomography. Muscle force was studied by jumping mechanography. RESULTS: In addition to an advanced bone maturation, differences in trabecular bone parameters (higher vBMD and larger trabecular area) and cortical bone geometry (larger cortical area and periosteal and endosteal circumference) were observed in ObAs both at the radius and tibia at different pubertal stages. After matching for bone age, all differences at the tibia, but only the difference in trabecular vBMD at the radius, remained significant. Larger muscle area and higher maximal force were found in ObAs compared with controls, as well as higher circulating free estrogen, but similar free testosterone and IGF-I levels. CONCLUSIONS: ObAs have larger and stronger bones at both the forearm and lower leg. The observed differences in bone parameters can be explained by a combination of advanced bone maturation, higher estrogen exposure, and greater mechanical loading resulting from a higher muscle mass and strength.

Protective embolization of the gastroduodenal artery with a one-HydroCoil technique in radioembolization procedures.

PURPOSE: Protective occlusion of the gastroduodenal artery (GDA) is required to avoid severe adverse effects and complications in radioembolization procedures. Because of the expandable features of HydroCoils, our goal was to occlude the GDA with only one HydroCoil to provide particle reflux protection. METHODS: Twenty-three subjects with unresectable liver tumors, who were scheduled for protective occlusion of the GDA before radioembolization therapy, were included. The primary end point was to achieve a proximal occlusion of the GDA with only one detachable HydroCoil. Evaluated parameters were duration of deployment, and early (during the intervention) and late (7-21 days) occlusion rates of GDA. Secondary end points included complete duration of the intervention, amount of contrast medium used, fluoroscopy rates, and adverse effects. RESULTS: In all cases, the GDA was successfully occluded with only one HydroCoil. The selected diameter/length range was 4/10 mm in 2 patients, 4/15 mm in 6 patients, and 4/20 mm in 15 patients. HydroCoils were implanted, on average, 3.75 mm from the origin of the GDA (range 1.5-6.8 mm), with an average deployment time of 2:47 (median 2:42, range 2:30-3:07) min. In 21 (91%) of 23 patients, a complete occlusion of the GDA was achieved during the first 30 min after the coil implantation; however, in all patients, a late occlusion of the GDA was present after 6 to 29 days. No clinical or technical complications were reported. CONCLUSION: We demonstrated that occlusion of the GDA with a single HydroCoil is a safe procedure and successfully prevents extrahepatic embolization before radioembolization.