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Summary Background Surgery is performed in many individuals with disorders/differences of sex development (DSD). Irreversibility of some surgical procedures, lack of information about the procedures, and lack of follow-up care for physical and psychological outcomes, lead to wish for more knowledge from both surgeons and patients. After the consensus conference in 2006, multidisciplinary care is provided to a higher degree with psychological support and more restricted surgical procedures. Outcome studies after genital surgery often lack of patient's perspective. Objective To describe surgical procedures in relation to diagnosis, to evaluate the outcomes of surgery through genital examination, and through patient's and observer's satisfaction with the anatomical and functional result after genital surgery. Study design In a cross-sectional clinical study performed in six European countries in 2014/15, we have included 500 participants where surgery was performed, from a total of 1040 adolescents (≥16years) and adults with a DSD. Diagnoses included Turner syndrome (n = 301), mixed gonadal dysgenesis (45,XO/46,XY; n = 45), Klinefelter syndrome (n = 218), XYY (n = 1), 46, XY DSD (n = 222) and 46, XX DSD (n = 253). Study protocol included clinical report files, an optional gynecological or urological examination, patient reported outcomes including received surgical interventions, satisfaction with appearance and function after surgery, and impact of the surgical procedure on life. Results Five hundred participants had received genital or breast surgery, with the highest rate in 46, XY DSD and the lowest in Turner syndrome. Altogether; 240 participants had feminizing surgery, 112 had masculinizing surgery, and 217 underwent gonadectomy. Physicians evaluated anatomical appearance at genital examination as poor in less than 10%. Dissatisfaction with anatomical appearance was reported by 22% of the participants, dissatisfaction with function by 20%. Being (very) dissatisfied with anatomical appearance and function was reported by 13% of the study participants. Most participants reported no impact, or positive impact, of the surgical procedures on their lives, but 29% experienced a negative effect of gonadectomy on their life. Discussion There might be a selection bias and/or a recall bias for participating in our studies. Due to poor data quality about surgical procedures performed in the past, we also relied on participants memory about surgical procedures in their past. Ideally, patient reported outcomes should be evaluated both before and after surgical procedures. Conclusion A vast majority are satisfied with appearance and function, but still genital or breast surgery have a long-lasting effect on patient's life. Self-reported satisfaction is usually lower than the observer's evaluation regarding both appearance and function. Download : Download high-res image (217KB) Download : Download full-size image Summary Figure . Satisfaction with anatomy and function after genital surgery in individuals with DSD (appearance: n = 244; function: n = 257) (n = total number of participants).

Background: Decreased bone mineral density (BMD) is a concern in patients with Congenital Adrenal Hyperplasia (CAH) due to lifelong glucocorticoid replacement. Studies till date have yielded conflicting results. We wanted to systematically evaluate the available evidence regarding BMD in adult patients with CAH. Methods: We searched Medline, Embase and Cochrane Central Register of Controlled Trials to identify eligible studies. Studies comparing BMD in CAH patients with age- and sex-matched controls were included. Age less than 16 years and absence of controls were exclusion criteria. Two authors independently reviewed abstracts, read full-text articles, extracted data, assessed risk of bias using Newcastle-Ottawa scale and determined level of evidence using Grading of Recommendations Assessment, Development and Evaluation methodology. Results: Nine case-control studies with a total sample size of 598 (cases n=254, controls n=344) met eligibility criteria. Total body BMD (Mean Difference [MD]-0.06; 95%CI -0.07, -0.04), lumbar spine BMD (MD -0.05; 95%CI -0.07, -0.03) and femoral neck BMD (MD -0.07; 95%CI -0.10, -0.05) was lower in cases compared to controls. Lumbar spine T-scores (MD -0.86; 95%CI -1.16, -0.56) and Z-scores (MD -0.66; 95%CI -0.99, -0.32) and femoral neck T-scores (MD -0.75 95%CI -0.95, -0.56) and Z-scores (MD -0.27 95%CI -0.58, 0.04) were also lower in cases compared to controls. No clear correlation between BMD and glucocorticoid dose was found. Conclusion: BMD in adult patients with CAH was lower compared to controls. Although no clear dose-response relationship between glucocorticoid dose and BMD was found, it would be prudent to avoid over-treatment with glucocorticoids.

Background: Surgery is the curative therapy for patients with medullary thyroid carcinoma (MTC). In determining the extent of surgery, the risk of complications should be considered. The aim of this study was to assess procedure-specific outcomes and risk factors for complications after surgery for MTC. Methods: Patients who underwent thyroid surgery for MTC were identified in two European prospective quality databases. Hypoparathyroidism was defined by treatment with calcium/active vitamin D. Recurrent laryngeal nerve (RLN) palsy was diagnosed on laryngoscopy. Complications were considered at least transient if present at last follow-up. Risk factors for at-least transient hypoparathyroidism and RLN palsy were identified by logistic regression analysis. Results: A total of 650 patients underwent surgery in 69 centres at a median age of 56 years. Hypoparathyroidism, RLN palsy and bleeding requiring reoperation occurred in 170 (26.2 per cent), 62 (13.7 per cent) and 17 (2.6 per cent) respectively. Factors associated with hypoparathyroidism were central lymph node dissection (CLND) (odds ratio (OR) 2.20, 95 per cent c.i. 1.04 to 4.67), CLND plus unilateral lateral lymph node dissection (LLND) (OR 2.78, 1.20 to 6.43), CLND plus bilateral LLND (OR 2.83, 1.13 to 7.05) and four or more parathyroid glands observed (OR 4.18, 1.46 to 12.00). RLN palsy was associated with CLND plus LLND (OR 4.04, 1.12 to 14.58) and T4 tumours (OR 12.16, 4.46 to 33.18). After compartment-oriented lymph node dissection, N0 status was achieved in 248 of 537 patients (46.2 per cent). Conclusion: Complications after surgery for MTC are procedure-specific and may relate to the unavoidable consequences of radical dissection needed in some patients., Novartis Health Alliance - Skane University Hospital Funds; AnnaLisa and Sven Lundgren Foundation, D.J.v.B. undertook this research while on the Sten Tibblin Fellowship, which was funded by Novartis Health Alliance. M.A. was funded by Skane University Hospital Funds, and the AnnaLisa and Sven Lundgren Foundation. The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. No preregistration exists for the study reported in this article. Because of the sensitive nature of the data collected for this study, the authors do not wish to make the data publicly available.

International audience; OBJECTIVE:To investigate fertility outcome in individuals with different forms of disorders of sex development (DSD), if assisted reproductive technology (ART) was used, and the patients' satisfaction with the information they had received.DESIGN:A cross-sectional multicenter study, dsd-LIFE.SETTING:Not applicable.PATIENT(S):A total of 1,040 patients aged ≥16 years with different DSD diagnoses participated.INTERVENTION(S):A web-based questionnaire was filled out by all participants. The participants could chose to take part in somatic investigations including ultrasonography.MAIN OUTCOME MEASURE(S):Information on partner, number of children, ART, adoption and step-children, general health, presence of gonads and uterus, current education and economic situation, received information on fertility issues, and satisfaction with the information, was collected.RESULT(S):In the total cohort, mean age 32 years, 33% lived with a partner, but only 14% reported having at least one child including 7% with ART, 4% adopted. Only 3.5% of the total cohort had been able to reproduce without ART, most frequently women with congenital adrenal hyperplasia, and only 0.7% of participants with other diagnoses. Of the participants, 72% had received information on fertility, but 17% were not satisfied with the information.CONCLUSION(S):Fertility outcome is significantly reduced in all types of DSD; however, fertility potential should be assessed individually. The satisfaction with how fertility problems have been discussed can be improved. The care of patients with DSD is complex, should be individualized, and new treatment possibilities incorporated. A close collaboration in multidisciplinary teams is therefore essential to improve the situation for individuals with DSD.

Background: In boys with suspected partial androgen insensitivity syndrome (PAIS), systematic evidence that supports the long-term prognostic value of identifying a mutation in the androgen receptor gene (AR) is lacking. Objective: To assess the clinical characteristics and long-term outcomes in young men with suspected PAIS in relation to the results of AR analysis. Methods: Through the International Disorders of Sex Development Registry, clinical information was gathered on young men suspected of having PAIS (n = 52) who presented before the age of 16 years and had genetic analysis of AR. Results: The median ages at presentation and at the time of the study were 1 month (range, 1 day to 16 years) and 22 years (range, 16 to 52 years), respectively. Of the cohort, 29 men (56%) had 20 different AR mutations reported. At diagnosis, the median external masculinization scores were 7 and 6 in cases with and without AR mutation, respectively (P = .9), and median current external masculinization scores were 9 and 10, respectively (P = .28). Thirty-five men (67%) required at least one surgical procedure, and those with a mutation were more likely to require multiple surgeries for hypospadias (P = .004). All cases with an AR mutation had gynecomastia, compared to 9% of those without an AR mutation. Of the six men who had a mastectomy, five (83%) had an AR mutation. Conclusions: Boys with genetically confirmed PAIS are likely to have a poorer clinical outcome than those with XY DSD, with normal T synthesis, and without an identifiable AR mutation. Routine genetic analysis of AR to confirm PAIS informs long-term prognosis and management., Using the I-DSD Registry, a study of long-term outcome in young men suspected of having PAIS in childhood reveals that outcome is clearly worse in those with a confirmed AR gene mutation.

A recent approach to personality measurement argues that the essential personality traits are encompassed by 5 basic factors: openness/intellect, conscientiousness, neuroticism, agreeableness, and extraversion. This study used the Big Five Inventory to test the hypothesis that 1 or more of the 5 factors underlie hypnotic suggestibility. No meaningful relationships between hypnotic suggestibility and any of the 5 factors were found.

Electrochemical treatment of cancer with DC electrodes changes the microenvironment of the cancer cells by electrophoresis. They may deteriorate and resorb. In larger neoplasms, the effects can be enhanced by electrophoresis of a chemotherapeutic agent. Adriamycin delivered into an electropositive neoplasm electrode will move outwards in the neoplastic area in a high concentration. When given intravenously and the neoplasm electrode is electronegative, the systemic effects may be diminished. The agent is instead accumulated in the neoplastic region in a high concentration. This principle may be used to reduce systemic effects of charged chemotherapeutic compounds. In this preliminary study of cancer in 14 patients, incurable with surgery, radiation treatment, or chemotherapy, beneficial effects were obtained after combined electrochemical treatment and the use of Adriamycin.

Motion parallax, the ability to recover depth from retinal motion generated by observer translation, is important for visual depth perception. Recent work indicates that the perception of depth from motion parallax relies on the slow eye movement system. It is well known that ethanol intoxication reduces the gain of this system, and this produces the horizontal gaze nystagmus that law enforcement's field sobriety test is intended to reveal. The current study demonstrates that because of its influence on the slow eye movement system, ethanol intoxication impairs the perception of depth from motion parallax. Thresholds in a motion parallax task were significantly increased by acute ethanol intoxication, whereas thresholds for an identical test relying on binocular disparity were unaffected. Perhaps a failure of motion parallax plays a role in alcohol-related driving accidents; because of the effects of alcohol on eye movements, intoxicated drivers may have inaccurate or inadequate information for judging the relative depth of obstacles from motion parallax.

Plasma pharmacokinetics of Adriamycin (doxorubicin) has been studied after intraneoplastic administration during electrochemical treatment to patients with lung cancer that is noncurable with radiotherapy, surgery, or chemotherapy. Intraneoplastic administration of Adriamycin via the anode resulted in a dramatic change of the pharmacokinetic pattern in plasma as compared with what has been previously observed after intravenous administration. A fivefold reduction of the area under the plasma concentration time curve and a 25-fold reduction of the maximum plasma concentration was observed.

The aim of this study was to determine bone mass at different skeletal sites in patients with end-stage liver disease and the effect of liver transplantation on bone mineralization.Bone mineral density in different skeletal regions was measured by photon absorptiometry in 25 patients with chronic liver disease, and the measurements were repeated in nine patients after orthotopic liver transplantation.In patients with liver failure bone mass values were not significantly different from those of controls. After liver transplantation bone mass decreased significantly during the first 6 posttransplant months at the distal radius, lumbar spine, and femur (p0.01) and was still below pretransplant values at the 12th posttransplant month. Serum osteocalcin increased significantly from the 3rd month after transplantation (from 6.9 +/- 4.4 to 12.0 +/- 6.5 micrograms/l; p0.0001) and remained increased throughout the first posttransplant year.Early and accelerated bone loss occurred after liver transplantation. This bone reduction seems to be mainly the result of increased bone resorption, possibly related to corticosteroid therapy.

Photon absorptiometry was used to measure skeletal mass in the proximal femur, lumbar spine, and distal radius in 19 females with hypoparathyroidism after operation for either thyroid carcinoma or hyperparathyroidism. Healthy subjects as well as normocalcemic patients who had undergone the same surgical procedure without developing hypoparathyroidism were used as controls. Skeletal mass was measured after a mean postoperative time of 13 and 10 yr in patients operated on for thyroid carcinoma and hyperparathyroidism, respectively. Bone mass was 10-32% greater in hypoparathyroid patients than in controls. In patients with retained parathyroid function after total thyroidectomy and surgical treatment of hyperparathyroidism, bone mass did not differ from that in age-matched healthy controls. Long term T4 medication in doses that suppressed endogenous TSH production was not associated with a decreased bone mass. Reduced PTH production, vitamin D treatment, and calcium supplementation may all have contributed to the increased bone mass found in the patients with postsurgical hypoparathyroidism.

(1957). Controlled puncture and contrast injection into the left ventricle of the heart. Acta Radiologica: Vol. 47, No. 1, pp. 33-45.

In the United States, glucose has been until recently the sole non-protein energy substrate utilized in total parenteral nutrition (TPN). However, recent reports show that the administration of massive glucose loads to surgical patients cause a high incidence of pulmonary and hepatic complications. Indirect calorimetry data indicate that these hypermetabolic patients seem to utilize endogenous fat preferentially to carbohydrate. Therefore, we have undertaken some studies on the metabolism of endogenous and exogenous fat. Peripheral lipolysis - as estimated by measurements of glycerol turnover - is increased after injury and during sepsis. There is not correlation between the turnover of glycerol and the plasma concentration in surgical patients. High glucose intake induces a marked decrease in the glycerol turnover of nutritionally depleted subjects but has only a slight effect on the lipolytic rate of injured and septic patients. The rates of free fatty acid turnover and oxidation are elevated in surgical patients. High carbohydrate loads reduce FFA oxidation rate less in hypermetabolic patients than in depleted subjects. The utilization of exogenous fat was studied by associating an estimation of the oxidation rate to the measure of the clearance after the injection of 14C -Intralipid in surgical patients. Both oxidation and clearance rates are increased in these patients in relation with the severity of the injury. A dissociation between the variations of the clearance and the oxidation rates was observed when TPN was given to surgical patients. In such conditions, the clearance rate does not indicate the further utilization of a fat emulsion. Administration of TPN containing exogenous fat seem to induce less pulmonary and hepatic complications than TPN with glucose alone. In conclusion, kinetic measurements are needed for studying the metabolism of endogenous fat in surgical patients. An increased utilization of endogenous and exogenous fat takes place in these patients. Including exogenous fat as part of their parenteral diet is indicated but the optimal proportion of glucose and fat has not been precisely determined yet.

(1955). Bronchography by the aspiration of contrast media. Acta Radiologica: Vol. 44, No. 4, pp. 281-288.

Difficulty in the accurate preoperative assessment of mitral insufficiency, clinically and by several laboratory methods, suggested the desirability of direct visualization of the regurgitant flow. Direct puncture of the left ventricle for the injection of radiopaque contrast material was used in dogs before and after the creation of mitral insufficiency by division of 1 chorda tendinea. The regurgitation was accurately recognized radiographically. Consistent alterations in left atrial border movement were also recorded by electrokymography.

Leptin, secreted from fat cells, functions as a lipostat mechanism through modulation of satiety signals. The role of leptin in humans has been only partly revealed. However, obese patients have markedly elevated levels of this hormone, and in both normal-weight and obese subjects there is a direct correlation between serum leptin levels and the percentage of body fat. The aim of the present study was to investigate the role of leptin and its relation to body fat content in chronic renal failure (CRF), a disorder associated with decreased appetite. Serum leptin levels and body composition (dual-energy x-ray absorptiometry) were measured in a cohort of 59 patients with terminal CRF (creatinine clearance rate, 8 +/- 1 ml/min). Sixteen of the patients were re-evaluated after 12 mo of peritoneal dialysis treatment, and eight patients were re-evaluated after 12 mo of hemodialysis treatment. The mean serum leptin concentrations were markedly higher (mean +/- SEM) in patients with CRF than in healthy control subjects matched for gender and body mass index (25.7 +/- 5.2 ng/ml versus 8.4 +/- 0.9 ng/ml; P0.001). Patients with ongoing signs of inflammation (C-reactive protein10 mg/L) demonstrated higher serum leptin levels (41.9 +/- 13.7 ng/ml versus 18.6 +/- 4.2 ng/ml; P0.05) than patients with normal C-reactive protein. A strong positive correlation (rho = 0.83; P0.0001) was found between serum leptin concentrations and the percentage of body fat. After 12 mo of peritoneal dialysis, the amount of body fat increased markedly (19.0 +/- 1.5 to 25.1 +/- 2.2 kg; P0.001), and the changes in serum leptin concentrations correlated significantly (rho = 0.69; P0.01) to the changes in the body fat content. In contrast, no significant changes in either body fat content or serum leptin levels were recorded in the eight patients that were re-evaluated after 12 mo of hemodialysis. Serum leptin concentrations are approximately three times higher in patients with CRF compared with healthy control subjects with a similar body mass index. In this study, it is also demonstrated that serum leptin is a good marker for the body fat content in CRF patients and correlates strongly to changes in body fat during 12 mo of peritoneal dialysis. These findings suggest that serum leptin could serve as a valuable clinical marker for the body fat content in patients with CRF. Further studies are needed to verify the hypothesis that increased serum leptin concentrations may contribute to uremic anorexia.

Background Although congenital adrenal hyperplasia (CAH) is known to be associated with adrenal crises (AC), its association with patient- or clinician-reported sick day episodes (SDE) is less clear. Methods Data on children with classic 21-hydroxylase deficiency CAH from 34 centers in 18 countries, of which 7 were Low or Middle Income Countries (LMIC) and 11 were High Income (HIC), were collected from the International CAH Registry and analyzed to examine the clinical factors associated with SDE and AC. Results A total of 518 children—with a median of 11 children (range 1, 53) per center—had 5388 visits evaluated over a total of 2300 patient-years. The median number of AC and SDE per patient-year per center was 0 (0, 3) and 0.4 (0.0, 13.3), respectively. Of the 1544 SDE, an AC was reported in 62 (4%), with no fatalities. Infectious illness was the most frequent precipitating event, reported in 1105 (72%) and 29 (47%) of SDE and AC, respectively. On comparing cases from LMIC and HIC, the median SDE per patient-year was 0.75 (0, 13.3) vs 0.11 (0, 12.0) (P Conclusions The real-world data that are collected within the I-CAH Registry show wide variability in the reported occurrence of adrenal insufficiency–related adverse events. As these data become increasingly used as a clinical benchmark in CAH care, there is a need for further research to improve and standardize the definition of SDE.

Item does not contain fulltext Context: It is well established that boys are heavier than girls at birth. Although the cause of birth weight (BW) difference is unknown, it has been proposed that it could be generated from prenatal androgen action. Objective: The aim of the current study was to determine the BW of children with disorders of sex development (DSD) of different etiologies and to evaluate the effects of androgen action on BW. Methods: Data regarding diagnosis, BW, gestational age, karyotype, and concomitant conditions were collected from the International Disorders of Sex Development (I-DSD) Registry (www.i-dsd). BW standard deviation score was calculated according to gestational age. Cases were evaluated according to disorder classification in I-DSD (i.e., disorders of gonadal development, androgen excess, androgen synthesis, androgen action, nonspecific disorder of undermasculinization groups, and Leydig cell defect). Results: A total of 533 cases were available; 400 (75%) cases were 46,XY, and 133 (25%) cases were 46,XX. Eighty cases (15%) were born small for gestational age (SGA). Frequency of SGA was higher in the 46,XY group (17.8%) than in the 46,XX (6.7%) group (P = 0.001). Mean BW standard deviation scores of cases with androgen excess and androgen deficiency [in disorders of gonadal development, androgen synthesis, and Leydig cell defect groups and androgen receptor gene (AR) mutation-positive cases in disorders of androgen action groups] were similar to normal children with the same karyotype. SGA birth frequency was higher in the AR mutation-negative cases in disorders of androgen action group and in the nonspecific disorders of the undermasculinization group. Conclusions: BW dimorphism is unlikely to be explained by fetal androgen action per se. 46,XY DSDs due to nonspecific disorders of undermasculinization are more frequently associated with fetal growth restriction, SGA, and concomitant conditions.

BACKGROUND AND OBJECTIVE: It is unclear whether the proportion of infants with a disorder of sex development who are raised as male or female has changed over time. The temporal trends in sex assignment of affected cases entered in the International Disorder of Sex Development (I-DSD) Registry were studied. METHODS: Cases of disorders of sex development reported as partial androgen insensitivity syndrome (PAIS; n = 118), disorder of gonadal development (DGD; n = 232), and disorder of androgen synthesis (DAS; n = 104) were divided into those who were born before 1990, 1990–1999, and after 1999. External appearance of the genitalia was described by the external masculinization score. RESULTS: The median (5th–95th percentile) external masculinization scores of those infants with PAIS, DGD, and DAS who were raised as boys were 6 (2–9), 6 (3–9), and 6 (1–12), respectively, and were significantly higher than in those raised as girls (2 [0–6], 2 [0–7], and 0 [0–5], respectively); this difference was maintained in the 3 temporal birth cohorts (P < .01). Of the 118 cases in the pre-1990 cohort, 41 (35%) were raised as boys; of the 148 cases in the 1990–1999 cohort, 60 (41%) were raised as boys; and of the 188 cases in the post-1999 cohort, 128 (68%) were raised as boys. CONCLUSIONS: Although there is an association between the external appearance of the genitalia and the choice of sex assignment, there are clear temporal trends in this practice pointing toward an increased likelihood of affected infants being raised as boys. The impact of this change in practice on long-term health outcomes requires additional focus.