Role of vitamin D levels and vitamin D supplementation on bone mineral density in Klinefelter syndrome.

UNLABELLED: This manuscript describes the role of low vitamin D in bone metabolism of Klinefelter subjects. Low vitamin D is frequent in this condition and seems to be more important than testosterone in inducing low bone mineral density (BMD) and osteoporosis. Supplementation with vitamin D restores BMD after 2 years of treatment, whereas testosterone alone seems to be ineffective. INTRODUCTION: Decreased bone mineral density (BMD) in Klinefelter syndrome (KS) is frequent, and it has been traditionally related to low testosterone (T) levels. However, low BMD can be observed also in patients with normal T levels and T replacement therapy does not necessarily increase bone mass in these patients. Nothing is known about vitamin D levels and supplementation in KS. In this study, we determine vitamin D status and bone mass in KS subjects and compare the efficacy of T therapy and vitamin D supplementation on BMD. METHODS: A total of 127 non-mosaic KS patients and 60 age-matched male controls were evaluated with reproductive hormones, 25-hydroxyvitamin D, PTH, and bone densitometry by dual-energy X-ray absorptiometry (DEXA). Patients with hypogonadism and/or 25-hydroxyvitamin D deficiency were treated with T-gel 2% and/or calcifediol and re-evaluated after 24 months of treatment. RESULTS: 25-hydroxyvitamin D levels were significantly lower in KS patients with respect to controls, and they had significantly lower lumbar and femoral BMD. The percentage of osteopenia/osteoporosis in subjects with 25-hydroxyvitamin D deficiency was higher with respect to subjects with normal 25-hydroxyvitamin D and was not related to the presence/absence of low T levels. Subjects treated with calcifediol or T + calcifediol had a significant increase in lumbar BMD after treatment. No difference was found in T-treated group. CONCLUSIONS: These data highlight that low 25-hydroxyvitamin D levels seem to have a more critical role than low T levels in inducing low BMD in KS subjects. Furthermore, vitamin D supplementation seems to be more effective than T replacement therapy alone in increasing BMD.

Altered bone status in unilateral testicular cancer survivors: Role of CYP2R1 and its luteinizing hormone-dependency.

BACKGROUND: Recent data suggest a potential role of testis in vitamin D activation, where Leydig cells could represent key players in this process since they express the highest amount of CYP2R1, a key enzyme involved in vitamin D 25 hydroxylation. AIM: To evaluate bone status in unilateral orchiectomy and to assess in vivo and in vitro LH-dependency of Vitamin D 25 hydroxylation. SUBJECTS AND METHODS: 125 normotestosteronemic patients with testicular cancer (TC), featured by unilateral orchiectomy and 41 age-matched healthy male controls were studied in the Center for Human Reproduction Pathology at the University of Padova. To evaluate LH-dependency of Vitamin D 25 hydroxylation in vitro, Leydig cell cultures were stimulated with hCG and assessed for CYP2R1 expression, whereas in vivo 10 hypogonadotropic hypogonadal (HH) patients were evaluated before and after treatment with gonadotropins for bone metabolism markers. Hormonal pattern and bone metabolism markers were measured in all subjects, whereas 105 patients and 41 controls underwent bone densitometry by DEXA. RESULTS: In TC patients 25-hydroxyvitamin D levels were significantly lower compared to controls. Furthermore, 23.8% of patients with TC displayed low bone density (Z-score <-2 SD). None of the 41 control subjects showed any significant alteration of BMD. In vitro and in vivo studies revealed that CYP2R1 expression in Leydig cells appeared to be hCG dependent. CONCLUSION: Our data show an association between TC and alteration of the bone status, despite unvaried androgen and estrogen levels, suggesting the evaluation of bone status and possible vitamin D deficiency in TC survivors.

In vitro steroid resistance correlates with outcome in severe alcoholic hepatitis.

UNLABELLED: Steroids improve the outcome in alcoholic hepatitis (AH), but up to 40% of patients fail to respond adequately. Interleukin-2 (IL-2) exacerbates steroid resistance in vitro. We performed a prospective study to determine if intrinsic steroid sensitivity correlates with response to steroids in individuals with severe AH and if IL-2 receptor blockade can reverse this. Peripheral blood mononuclear cells (PBMCs) were isolated from 20 patients with AH and a Maddrey's score >32. Patients were treated with oral prednisolone plus full supportive measures. Clinical resistance to oral steroid treatment was defined as a drop in serum bilirubin of <25% within 7 days or death within 6 months. In vitro steroid resistance was measured in PBMC using the dexamethasone suppression of lymphocyte proliferation assay and repeated after the addition of the anti-IL-2 receptor (anti-CD25) monoclonal antibody, basiliximab. Suppression of lymphocyte proliferation <60% was considered to indicate steroid resistance. In all, 82% (9/11) of in vitro steroid-resistant patients were dead at 6 months as compared to 21% (2/9) of steroid-sensitive patients (P = 0.03). Similarly, 91% (10/11) of in vitro steroid-resistant patients failed to show a significant fall in bilirubin at day 7 as compared to 44% (4/9) of steroid-sensitive patients (P < 0.05). Basiliximab improved the maximal proliferation count in 91% (10/11) of in vitro steroid-resistant patients (P = 0.003). CONCLUSION: Clinical outcome of steroid therapy in this patient cohort correlated with in vitro steroid resistance. IL-2 blockade improved in vitro steroid sensitivity. This suggests that intrinsic lack of steroid sensitivity may contribute to poor clinical response to steroids in severe AH. IL-2 receptor blockade represents a possible mechanism to overcome this.

Space Flight-Promoted Insulin Resistance as a Possible Disruptor of Wound Healing.

During space flight, especially when prolonged, exposure to microgravity results in a number of pathophysiological changes such as bone loss, muscle atrophy, cardiovascular and metabolic changes and impaired wound healing, among others. Interestingly, chronic low-grade inflammation and insulin resistance appear to be pivotal events linking many of them. Interestingly, real and experimental microgravity is also associated to altered wound repair, a process that is becoming increasingly important in view of prolonged space flights. The association of insulin resistance and wound healing impairment may be hypothesized from some dysmetabolic conditions, like the metabolic syndrome, type 2 diabetes mellitus and abdominal/visceral obesity, where derangement of glucose and lipid metabolism, greater low-grade inflammation, altered adipokine secretion and adipocyte dysfunction converge to produce systemic effects that also negatively involve wound healing. Indeed, wound healing impairment after traumatic events and surgery in space remains a relevant concern for space agencies. Further studies are required to clarify the molecular connection between insulin resistance and wound healing during space flight, addressing the ability of physical, endocrine/metabolic, and pharmacological countermeasures, as well as nutritional strategies to prevent long-term detrimental effects on tissue repair linked to insulin resistance. Based on these considerations, this paper discusses the pathophysiological links between microgravity-associated insulin resistance and impaired wound healing.

Technological innovation of Continuous Glucose Monitoring (CGM) as a tool for commercial aviation pilots with insulin-treated diabetes and stakeholders/regulators: A new chance to improve the directives?

Civil aviation pilots who develop insulin-treated diabetes and want to renew a Commercial Pilot License (CPL) represent a medical, social and regulatory problem. This depends on justified concerns about hypoglycemia, the most threatening event for people who carry out jobs requiring a high level of concentration and reliability. This negatively affects social and working aspects of pilots' lives, who have a high profile and a high-cost professional qualification. It could be possible now to revise this attitude thanks to the availability of Continuous Glucose Monitoring (CGM) devices. CGM clearly showed to prevent hypoglycemic events in insulin-treated diabetic patients by allowing strict monitoring and trend prediction of glucose levels. By systematizing available data on such devices and present regulations in CPL issuance worldwide, our review can be used as handy tool for a fruitful discussion among the scientific community, national and international civil aviation regulators, stakeholders and pilots, aimed at evaluating the evidence-based opportunity to revise CPL issuance criteria for insulin-treated diabetic pilots. For the above-mentioned reasons, there are, among the regulatory administrations of Civil Aviation around the globe, several different approaches and limitations set for the subjects with insulin-treated diabetes who want to obtain, or renew, a CPL.

Osteoporosis in Klinefelter's syndrome.

Hypogonadism represents one of the most important causes of male osteoporosis. Testosterone regulates male bone metabolism both indirectly by aromatization to estrogens and directly through the androgen receptor (AR) on osteoblasts, promoting periosteal bone formation during puberty and reducing bone resorption during adult life. Early onset of testosterone deficiency, as observed in Klinefelter's syndrome (KS), is an important risk factor for precocious osteoporosis. Osteoporosis is present in up to 40% of subjects with KS and has usually been attributed to low testosterone levels. However, reduced bone mass might be present also in KS men with normal testosterone levels and testosterone replacement therapy does not always restore bone density in KS patients. Possible new determinants for osteoporosis in KS might be related to the AR function and insulin-like factor 3 (INSL3) levels. The CAG length and inactivation pattern of the AR in KS have been related to osteoporosis, but definitive proof is lacking. INSL3 has an anabolic role on bone metabolism by acting on osteoblasts and INSL3 levels are low in KS. Therefore, low INSL3 concentrations might represent a possible new pathogenic mechanism for reduced bone mass in KS.

Endothelial progenitor cells as a new cardiovascular risk factor in Klinefelter's syndrome.

Klinefelter syndrome (KS) is associated with a significant reduced life expectancy (2.1 years) including greater mortality from cardiovascular diseases. Underlying causes that may involve low levels of testosterone as well as the extra X chromosome are not fully understood. Low testosterone may have a direct affect on vascular tissue or act indirectly via metabolic effects. Testosterone levels may act genomically on cardiac function via the androgen receptor (AR) or non-genomically. Recently, it has been demonstrated that a reduced number of circulating endothelial progenitor cells (EPCs) is an independent predictor of morbidity and mortality from cardiovascular diseases. Because EPCs have never been studied in KS, we evaluated the number of circulating EPCs in 68 adult 47,XXY Klinefelter men and 46 healthy males. Patients and controls were divided into two groups, according to the absence or presence of cardiovascular risk factors (CRFs). Controls without CRFs had significantly higher levels of EPCs than controls with CRFs; on the contrary, KS patients without CRFs had EPCs levels similar to KS men with risk factors and significantly lower with respect to controls without CRFs. The number of EPCs in patients with hypogonadism was not different from that of those with normal testosterone levels. Twenty-two hypogonadal patients were re-evaluated after 6 months of androgen therapy, but we did not observe any modification in the number of EPCs. These primary hypothesis-generating data suggest that factors involved in KS, whether hypogonadism, CRFs or other genetically determined factors related to the supernumerary X chromosome might contribute to a reduction in EPCs number and that this could be considered another CRF contributing to the increased mortality of these subjects.

Increased osteocalcin-positive endothelial progenitor cells in hypogonadal male patients.

OBJECTIVE: Endothelial dysfunction is considered a key factor in the development of cardiovascular diseases. Endothelial regeneration is necessary for the maintenance of endothelial function and circulating endothelial progenitor cells (EPC) participate of it in both direct and indirect manner. The molecular phenotype of EPC is not univocally defined and recent studies identified an osteocalcin (OCN)-positive (EPC-OCN+) subpopulation of EPC highly correlated with atherosclerosis progression. AIM: Considering that hypogonadism is a risk factor for cardiovascular diseases and atherosclerosis, we investigated the circulating levels of EPC-OCN+ in hypogonadal patients. SUBJECTS AND METHODS: Ten hypogonadotropic hypogonadal (HH) male patients and 30 healthy eugonadal men were evaluated for clinical status and hormonal levels. Circulating levels of CD34+/CD133+/kinase insert domain-receptor+ EPC and EPC-OCN+ were also determined by flow cytometry. RESULTS: Compared to controls, HH patients displayed lower FSH, LH, estradiol, testosterone, and EPC levels. On the contrary, EPC-OCN+ were significantly increased. CONCLUSIONS: The observed association of low levels of circulating EPC and increased values of EPC-OCN+ sub-population in hypogonadal men strengthens the significance of hypogonadism as cardiovascular risk factor.

Spermatogenesis in Klinefelter syndrome.

BACKGROUND: Klinefelter syndrome (KS) (47,XXY) is the most common sex chromosomal disorder, and it is a frequent form of male hypogonadism and infertility. Although the majority of these patients are azoospermic, they might have severe oligozoospermia or residual single-residual foci with spermatogenesis in the testis. AIM: We report our experience on sperm retrieval in the ejaculate and testis, and evaluate the frequency of chromosome abnormalities in sperm of KS. SUBJECTS AND METHODS: Eighty-four 47,XXY KS were evaluated with seminal analysis, body hair distribution, reproductive hormones, ultrasonographic scanning of the testis and prostate, bilateral testicular sperm extraction (TESE), sperm or testicular cells sex chromosomes aneuploidies. RESULTS: Out of 84 patients, 7 (7/84; 8.3%) had sperm in the ejaculate. Out of the 77 azoospermic patients, 24 underwent TESE and 9 (9/24; 37.5%) had successful sperm recovery. The comparison of reproductive hormones, age and testicular volume did not show significant differences between patients with and without successful sperm recovery in semen or TESE . Patients without successful sperm recovery in semen analysis or TESE had signs of hypoandrogenism more evident than patients with successful sperm recovery. Patients with KS produced a higher number of sperm aneuploidy with respect to normozoospermic fertile controls and non-genetic severely oligozoospermic men. CONCLUSIONS: Men with KS are not always sterile. In some of these patients sperm can be found in semen or in the testis, but the proportion of sperm aneuploidy is high. Signs of hypoandrogenism seem to be associated with low sperm recovery rate.

A single-institution restrospective experience of brachytherapy in the treatment of pituitary tumors: transsphenoidal approach combined with (192)Ir-afterloading catheters.

BACKGROUND AND AIM: Radiotherapy may be used as an adjuvant treatment of pituitary adenomas. The aim of our study was to present our experience of multimodal treatment of pituitary adenomas, consisting in temporary implantation of (192)Ir-labeled wires following transphenoidal surgery. SUBJECTS AND METHODS: An observational investigation was performed on a series of 80 patients undergoing surgery (S) for pituitary adenomas between 1982 and 2000, some of whom received post-operative external beam radiotherapy (EBRT) (no.=19 between 1982 and 1990), brachytherapy (B) (no.=35, all after 1991), or both irradiation modalities (EBRT+B) (no.=14). The different treatments were compared in terms of hormonal normalization in the subgroup of patients with hypersecreting adenomas, tumor control, and side effects. RESULTS: Hormonal normalization was obtained in 84% of S+B patients and in 61% of S+EBRT patients. Tumor control was obtained in 74.3% of S+B patients and in 63.1% of S+EBRT patients. Anterior pituitary hormones deficits ranged from 8.6-34% in S+B patients and from 15.8-47.4% in S+EBRT patients, after a mean follow-up of 14 yr. The latter group also showed a higher rate of multiple deficits (42.1% vs 22.8%). Diabetes insipidus and other major complications were rare events in all groups. CONCLUSIONS: We presented one original experience regarding brachytherapy in the management of pituitary tumors, which turned out to be effective and safe. Additional prospective, and possibly randomized, studies should clarify whether in the era of 3-dimensional conformal radiotherapy and stereotactic radiotherapy this treatment modality may still have a role.

Endocrine and psychological aspects of sexual dysfunction in Klinefelter patients.

Klinefelter syndrome is a frequent cause of hypogonadism, but despite hundreds of publications on different aspects of Klinefelter syndrome, only a few studies dealt with sexual dysfunction. In particular, testosterone is critical for various aspects of sexual response, but its role on sexuality in Klinefelter syndrome patients is debatable and no studies have evaluated the efficacy of testosterone treatment on sexual dysfunction in these subjects. Furthermore, the impact of psychological and relational aspects on sexual function of Klinefelter syndrome subjects is poorly defined. In this study, we aimed to determine the presence and type of sexual dysfunctions in Klinefelter syndrome subjects; to correlate them with testosterone levels and psychosexological and relational domains; and to evaluate the effects of testosterone therapy. We studied 62 non-mosaic naïve Klinefelter syndrome patients and 60 age-matched controls by means of medical history, psychosexological history, 15-item International Index of Erectile Function questionnaire, endocrine assessment, and dynamic penile color Doppler ultrasound. Twenty-five hypogonadal Klinefelter syndrome patients were studied after 6 months of testosterone replacement therapy. Klinefelter syndrome subjects have reduced 15-item International Index of Erectile Function scores regarding sexual desire, intercourse satisfaction, and overall satisfaction with respect to controls, and these aspects were significantly associated with testosterone levels. Klinefelter syndrome subjects had also higher prevalence of erectile dysfunction, but no relation with testosterone levels was evident. A high prevalence of a range of psychological disturbances was present in Klinefelter syndrome subjects with erectile dysfunction with respect to those without erectile dysfunction. No statistical difference in the prevalence of premature and delayed ejaculation was observed between Klinefelter syndrome and control subjects. Testosterone replacement therapy improved sexual desire, intercourse satisfaction, and overall satisfaction scores, but had no effect on erectile function. Penile color Doppler ultrasound was normal in all subjects. This study shows that sexual dysfunction in Klinefelter syndrome is multifactorial and related only in part to hypogonadism and largely to psychological disturbances. Evaluation and therapy of sexual dysfunction should include a combined andrological and psychosexological approach.

Hyponatremia and pituitary adenoma: think twice about the etiopathogenesis.

Pituitary adenomas may be the cause of the syndrome of inappropriate secretion of antidiuretic hormone (SIADH), although few cases have so far been reported. We described a case of hypotonic hyponatremia in a 76-yr-old man with a pituitary macroadenoma. He had a recent history of two syncopal attacks which had occurred in the last two months. Baseline assessment demonstrated a sodium serum level of 114 mEq/l. Clinically, the patient appeared euvolemic. Thyroid and adrenal function testing did not show any abnormality. Plasma and urinary osmolality (238 and 186 mOsm/kg, respectively) were in agreement with the diagnosis of SIADH. Accordingly, 3% hypertonic saline solution was started, followed by water intake restriction when natremia reached 126 mEq/l. A computed tomography (CT) scan of the chest revealed the presence of a 2-cm lesion in the azygos-esophageal recess. Because the nature of the lesion appeared uncertain, antibiotic therapy was initiated. After one month, a new CT scan did not show any evidence of the mediastinic mass. Sodium serum level was within the normal range (141 mEq/l) and remained stable thereafter, without fluid restriction. This case very well demonstrates that, in the presence of hyponatremia due to SIADH, more frequently associated co-morbidities (ie mediastinic diseases) have to be searched, even in the presence of a possible, yet rare, cause of this syndrome (ie pituitary adenoma).

Minimally invasive corticotomy in orthodontics using a three-dimensional printed CAD/CAM surgical guide.

The aim of this prospective study was to evaluate the effectiveness of an innovative, minimally invasive, flapless corticotomy procedure in orthodontics. The STROBE guidelines were followed. Ten patients with severe dental crowding and a class I molar relationship were selected to receive orthodontic treatment with clear aligners and corticotomy-facilitated orthodontics. The mean age of these patients was 21 years (range 17-28, standard deviation 6.08 years); the male to female ratio was 2:1. The main outcome was a reduction in the total treatment time to correct dental crowding. The secondary outcomes were periodontal index changes, the degree of root resorption, and patient perceptions of the method used, assessed using the short-form Oral Health Impact Profile (OHIP-14). The occurrence of early surgical complications or unexpected events was also recorded. All patients completed the treatment to correct dental crowding. The average treatment time was reduced by two-thirds. The procedure did not significantly modify the periodontal indices or oral health-related quality of life. No early surgical complications or unexpected events were observed. In short, the results indicate that this new procedure is safe and accelerates tooth movement without periodontal complications or discomfort. However, the efficacy of this procedure must be confirmed in controlled clinical trials.

The Klinefelter syndrome is associated with high recurrence of copy number variations on the X chromosome with a potential role in the clinical phenotype.

The Klinefelter syndrome (KS) is the most frequent sex chromosomal disorder in males, characterized by at least one supernumerary X chromosome (most frequent karyotype 47,XXY). This syndrome presents with a broad range of phenotypes. The common characteristics include small testes and infertility, but KS subjects are at increased risk of hypogonadism, cognitive dysfunction, obesity, diabetes, metabolic syndrome, osteoporosis, and autoimmune disorders, which are present in variable proportion. Although part of the clinical variability might be linked to a different degree of testicular function observed in KS patients, genetic mechanisms of the supernumerary X chromosome might contribute. Gene-dosage effects and parental origin of the supernumerary X chromosome have been suggested to this regard. No study has been performed analyzing the genetic constitution of the X chromosome in terms of copy number variations (CNVs) and their possible involvement in phenotype of KS. To this aim, we performed a SNP arrays analysis on 94 KS and 85 controls. We found that KS subjects have more frequently than controls X-linked CNVs (39/94, [41.5%] with respect to 12/42, [28.6%] of females, and 8/43, [18.6%] of males, p < 0.01). The number of X-linked CNVs in KS patients was 4.58 ± 1.92 CNVs/subject, significantly higher with respect to that found in control females (1.50 ± 1.29 CNVs/subject) and males (1.14 ± 0.37 CNVs/subject). Importantly, 94.4% X-linked CNVs in KS subjects were duplications, higher with respect to control males (50.0%, p < 0.001) and females (83.3%, p = 0.1). Half of the X-linked CNVs fell within regions encompassing genes and most of them (90%) included genes escaping X-inactivation in the regions of X-Y homology, particularly in the pseudoautosomal region 1 (PAR1) and Xq21.31. This study described for the first time the genetic properties of the X chromosome in KS and suggests that X-linked CNVs (especially duplications) might contribute to the clinical phenotype.

Early peri-implant bone loss: a prospective cohort study.

The aim of this study was to measure the early peri-implant bone level changes before the completion of an implant-abutment connection and to evaluate the influence of demographic, biologically relevant, anatomical, and implant-specific variables on these changes. A prospective cohort study design was used. STROBE guidelines were followed. The sample comprised 493 implants placed using a two-stage surgical procedure. Random allocation was used to determine the implant placement depth. Peri-apical radiographs taken at implant insertion and at the second surgery 2 months later were matched. Kappa statistics were used to compute intra- and inter-examiner reliability. The statistical analysis was performed at the implant level. Two-way analysis of variance (ANOVA) with the Bonferroni adjusted post hoc test was used to evaluate the influence of variables. One-way ANOVA with Tukey's range test and unpaired Student t-tests were used to analyze significant variables. Early marginal bone remodelling was -0.86 mm. The timing of implant placement (P=0.00) and the depth of implant placement (P≤0.05) significantly influenced early bone remodelling. Relevant radiographic early bone loss was found, but implants initially positioned below the alveolar crest and inserted ≥3 months after tooth extraction showed statistically significant higher marginal bone loss during the healing phase.

How does an error in positioning the template affect the accuracy of implants inserted using a single fixed mucosa-supported stereolithographic surgical guide?

Computer-aided implantology using a single fixed stereolithographic surgical guide involves a sequence of diagnostic and therapeutic events, and errors can creep in at different stages. Taken together, these can be termed the 'total error'. A positioning of the surgical guide on the support surface different to that of the diagnostic template may generate an error that reoccurs with all the implants inserted, and this error can be termed the 'guide positioning error'. The aim of the present study was to measure the deviation between the planned and inserted implants due to this guide positioning error, to evaluate if this error was statistically significant, and concurrently, to assess the influence of the type of arch (upper vs lower jaw) and mucosal thickness on the guide positioning error. Twenty-four subjects were treated and 172 implants inserted. Preoperative and postoperative computed tomography images were compared using Mimics software to determine the total error and guide positioning error. Quantitative data were described; the t-test and Pearson correlation coefficient were used. The guide positioning error was found to affect the accuracy, but was statistically significant only for global coronal deviation (P = 0.038). Arch of support and mucosa thickness did not affect the guide positioning error.

Is it possible to improve the accuracy of implants inserted with a stereolithographic surgical guide by reducing the tolerance between mechanical components?

When using a stereolithographic surgical guide, a potentially clinically relevant error may be the mechanical error caused by the bur guide cylinder gap due to the presence of a rotational allowance of drills in the tubes. The aim of the present study was to determine if it is possible to reduce the total error by limiting the tolerance among the mechanical components and to evaluate its clinical incidence. Sixty implants were inserted in eight totally edentate subjects using the External Hex Safe(®) system with mechanical components modified to minimize the tolerance. Pre- and postoperative computed tomography images were compared, and the angular deviation was calculated between the planned and the placed implants. The mean angular deviation was 2.02° (range 0.81-3.48°; standard deviation 0.87). The results of the present study show that by limiting the error that originates from mechanical components, the total error could be significantly reduced.

The intrinsic error of a stereolithographic surgical template in implant guided surgery.

The aim of the present study was to assess the clinical relevance of the potential mechanical error (intrinsic error) caused by the cylinder-burr gap in a 'single type' stereolithographic surgical template in implant guided surgery. 129 implants were inserted in 12 patients using 18 templates. The pre- and postoperative computed tomography (CT) scans were matched allowing comparison of the planned implants with the placed ones. Considering only the angular deviation values, the t test was used to determine the influence of the guide fixation and the arch of support on accuracy values. The Pearson correlation coefficient was used to correlate angular deviation and bone density. The intrinsic error was mathematically evaluated. t test results indicated that the use of fixing screws (P=009) and the upper arch support (P=027) resulted in better accuracy. The Pearson correlation coefficient (0.229) indicated a significant linear correlation between angular deviations and bone density (P=009). A mean intrinsic error of 2.57 was mathematically determined considering only the angular deviation, as it was not influenced by other variables. The intrinsic error is a significant factor compared to all the variables that could potentially affect the accuracy of computer-aided implant placement.

Prostate volume and growth during testosterone replacement therapy is related to visceral obesity in Klinefelter syndrome.

OBJECTIVE: Klinefelter syndrome (KS) is a chromosomal alteration characterized by increased risk of metabolic syndrome, mainly caused by visceral obesity. In the last years, obesity has been studied as a potential risk factor for prostate disease and recently a link has been demonstrated between visceral adiposity with prostate volume. The aim of this study was to analyze the relationship between obesity and prostate volume and growth during testosterone therapy in KS subjects. DESIGN AND METHODS: We evaluated reproductive hormones, metabolic parameters, anthropometric measures, PSA, and prostate volume in 121 naïve non-mosaic KS patients and 60 age-matched healthy male controls. Fifty-six KS hypogonadic subjects were treated with testosterone-gel 2% and reevaluated after 18 months of treatment. RESULTS: Prostate volume in KS was positively related to waist circumference (WC). The KS group with WC ≥94 cm had significantly higher prostate volume, BMI, insulin plasma levels, homeostasis model assessment index, total cholesterol, triglycerides, and glycemia with respect to the KS group with WC <94 cm. After testosterone replacement therapy, only hypogonadic KS men with WC ≥94 cm had a statistically significant increase in prostate volume. Furthermore, in untreated KS subjects, prostate volume showed a statistically significant increase after 18 months of follow-up only in subjects with WC ≥94 cm. CONCLUSIONS: This study showed that visceral obesity, insulin resistance, and lipid and glucose metabolism alterations are associated with prostate volume and growth during testosterone replacement therapy in KS, independently from androgen or estrogen levels. These latter findings might provide the basis for a better management and follow-up of KS subjects.

Depth deviation and occurrence of early surgical complications or unexpected events using a single stereolithographic surgi-guide.

The purpose of this study was to determine the accuracy of depth implant insertion and to describe the frequency of early surgical complications or unexpected events, recorded using a single, totally guided, stereolithographic surgi-guide (bone-, mucosa- and teeth-supported) for both osteotomy site preparation and implant delivery. Ten adults were included in this study. Six patients were treated in both arches, and the number of computer aided implantology (CAI) interventions was 16, which equalled the number of guides used, for a total of 111 implants inserted. Complications and unexpected events occurred during the positioning of the surgical guide and whilst preparing the implant site and installing implants. In order to minimize the risk of complications and unexpected events, attention must be paid to every stage of treatment, including checking computed tomography (CT) images, guide manufacturing, proper guide positioning in the mouth, guide fixation, rotational allowance of drill in tubes, shape and sharpness of the drills, first entry point, mouth opening and guided implant insertion.