Epidemiology of proximal and diaphyseal humeral fractures in children: an observational study from the Swedish Fracture Register.

BACKGROUND: Most fractures in children are fractures of the upper extremity. Proximal and diaphyseal humeral fractures account for a minority of these fractures. To our knowledge, few previous reports address these fractures. This study aimed to describe the epidemiology and current treatment of proximal and diaphyseal humeral fractures by using the Swedish Fracture Register (SFR). METHODS: In this nationwide observational study from the SFR we analysed data on patient characteristics, injury mechanism, fracture classification and treatment. We included patients aged < 16 years at time of injury with proximal or diaphyseal humeral fracture registered in 2015-2019. RESULTS: 1996 (1696 proximal and 300 diaphyseal) fractures were registered. Proximal fractures were more frequent in girls whereas diaphyseal fractures were more frequent in boys. The median age at fracture was 10 years in both fracture types but patient's age was more widespread in diaphyseal fracture (IQR 5-13 compared to IQR 7-12 in proximal). In both sexes, the most registered injury mechanism was fall. Horse-riding was a common mechanism of injury in girls, whereas ice-skating and skiing were common mechanisms in boys. Most proximal fractures were metaphyseal fractures. Most diaphyseal fractures were simple transverse or oblique/spiral fractures. The majority of fractures were treated non-surgically (92% of proximal and 80% of diaphyseal fractures). The treatment method was not associated with the patient's sex. Surgery was more often performed in adolescents. The most common surgical methods were K-wire and cerclage fixation in proximal fracture and intramedullary nailing in diaphyseal fracture. CONCLUSION: Following falls, we found sex-specific sport activities to cause most proximal and diaphyseal paediatric fractures. Further studies on prophylactic efforts in these activities are needed to investigate whether these fractures are preventable. The majority of the fractures were treated non-surgically, although surgical treatment increased with increasing age in both sexes. TRIAL REGISTRATION: Not applicable. The present study is a register-based cohort study. No health care intervention had been undertaken.

Incidence and Clinical Presentation of Pheochromocytoma and Sympathetic Paraganglioma: A Population-based Study.

CONTEXT: Pheochromocytoma and sympathetic paraganglioma (PPGL) are rare catecholamine-secreting tumors but recent studies suggest increasing incidence. Traditionally, PPGL are described to present with paroxysmal symptoms and hypertension, but existing data on clinical presentation of PPGL come from referral centers. OBJECTIVE: We aimed to describe time trends in clinical presentation and incidence of PPGL in a population-based study. METHODS: We conducted a nationwide retrospective cohort study of a previously validated cohort of 567 patients diagnosed with PPGL in Denmark 1977-2015. We collected clinical data from medical records of a geographic subcohort of 192 patients. We calculated age-standardized incidence rates (SIRs) and prevalence for the nationwide cohort and descriptive statistics on presentation for the subset with clinical data. RESULTS: SIRs increased from 1.4 (95% CI 0.2-2.5) per million person-years in 1977 to 6.6 (95% CI 4.4-8.7) per million person-years in 2015, corresponding to a 4.8-fold increase. The increase was mainly due to incidentally found tumors that were less than 4 cm and diagnosed in patients older than 50 years with no or limited paroxysmal symptoms of catecholamine excess. On December 31, 2015, prevalence of PPGL was 64.4 (CI 95% 57.7-71.2) per million inhabitants. Of 192 patients with clinical data, 171 (89.1%) had unilateral pheochromocytoma, while unilateral paraganglioma (n = 13, 6.8%) and multifocal PPGL (n = 8, 4.2%) were rare. CONCLUSION: Incidence of PPGL has increased 4.8-fold from 1977 to 2015 due to a "new" group of older patients presenting with smaller incidentally found PPGL tumors and few or no paroxysmal symptoms.

Leader cell PLCγ1 activation during keratinocyte collective migration is induced by EGFR localization and clustering.

Re-epithelialization is a critical step in wound healing and results from the collective migration of keratinocytes. Previous work demonstrated that immobilized, but not soluble, epidermal growth factor (EGF) resulted in leader cell-specific activation of phospholipase C gamma 1 (PLCγ1) in HaCaT keratinocytes, and that this PLCγ1 activation was necessary to drive persistent cell migration. To determine the mechanism responsible for wound edge-localized PLCγ1 activation, we examined differences in cell area, cell-cell interactions, and EGF receptor (EGFR) localization between wound edge and bulk cells treated with vehicle, soluble EGF, or immobilized EGF. Our results support a multistep mechanism where EGFR translocation from the lateral membrane to the basolateral/basal membrane allows clustering in response to immobilized EGF. This analysis of factors regulating PLCγ1 activation is a crucial step toward developing therapies or wound dressings capable of modulating this signal and, consequently, cell migration.

Androgen Receptor Polymorphism and Female Sexual Function and Desire.

INTRODUCTION: The effect of testosterone depends on the exposure of and the sensitivity of the androgen receptor (AR). It has been shown that a cytosine-adenine-guanine (CAG) trinucleotide repeat polymorphism in the AR gene has an impact on AR functional capacity in men. However, large studies are lacking on the impact of this polymorphism on female sexual function. AIM: To determine whether the CAG repeat length was associated with different aspects of women's sexual function and dysfunction, including desire, arousal, lubrication, orgasm, satisfaction, sexual pain, and sexually related personal distress. METHODS: This cross-sectional study included 529 healthy women, aged 19-65 years. Participants completed a questionnaire to provide demographic and sexual data. The CAG repeat length was analyzed in a blood sample. The correlations between CAG repeat lengths and different aspects of sexual function were calculated. Independent Student t-tests were performed to evaluate differences in the mean number of CAG repeats in the short and long allele and of the biallelic mean length determined by simple calculation and X-inactivation analysis, respectively, between women with sexual problems and women without sexual problems. P values <.05 were considered statistically significant. MAIN OUTCOME MEASURE: We used the Female Sexual Function Index, with 6 subdomains, to distinguish between women without and women with impaired sexual function; low sexual desire; impaired arousal, lubrication, or orgasm; diminished satisfaction; or pain during sex. The Female Sexual Distress Scale was used to measure sexually related personal distress. RESULTS: Overall, we found that increasing numbers of CAG repeats were correlated to increased sexual function. We found that women with problems achieving orgasm had a significantly lower number of CAG repeats than women that reported no problems reaching orgasm. We found no associations between CAG repeat lengths and other aspects of female sexual dysfunction, including hypoactive sexual desire disorder. CLINICAL IMPLICATIONS: The results could indicate an impact of the AR on women's sexual function, including the ability to reach orgasm. STRENGTH & LIMITATIONS: This is a large study using validated sexual questionnaires. A limitation is the cross-sectional design. Owing to the study design, this study is explorative and hypothesis generating. CONCLUSION: In this large cross-sectional study, we demonstrated that CAG repeat length is positively correlated to sexual function and that women with a reduced ability to reach orgasm had smaller numbers of CAG repeats in the AR gene than women with no orgasmic problems. These findings indicated that androgens and ARs might play a role in women's sexual function. Wåhlin-Jacobsen S, Flanagan JN, Pedersen AT, Kristensen E, Arver S, Giraldi A. Androgen Receptor Polymorphism and Female Sexual Function and Desire. J Sex Med 2018;15:1537-1546.

Pheochromocytoma in Denmark during 1977-2016: validating diagnosis codes and creating a national cohort using patterns of health registrations.

BACKGROUND: Pheochromocytoma and catecholamine-secreting paraganglioma (PPGL) are rare but potentially life-threatening tumors. We aimed to validate diagnosis codes for PPGL in the Danish National Patient Registry, the Danish National Pathology Registry, and the Danish Registry of Causes of Death and to create a national cohort of incident PPGL patients by linking these three registries. PATIENTS AND METHODS: We obtained data from the three abovementioned registries for all individuals registered with pheochromocytoma or catecholamine hypersecretion in Denmark during 1977-2016 (average population 5.30 million). We then reviewed health records for all individuals living in the North Denmark Region and Central Denmark Region (average population 1.75 million) to validate the diagnosis of PPGL. We tested a number of algorithms for accurately identifying true cases of PPGL to maximize positive predictive values (PPVs) and completeness. The best algorithm was subsequently validated in an external sample. RESULTS: We identified 2626 individuals with a PPGL diagnosis code in Denmark, including 787 (30.0%) in the North Denmark Region and Central Denmark Region. In this subsample, we retrieved the health records of 771/787 (98.0%) individuals and confirmed 198 incident PPGL patients (25.3%). The PPV of PPGL diagnosis codes was 21.7% in the Danish National Patient Registry, 50.0% in the Danish Registry of Causes of Death, and 79.5% in the Danish National Pathology Registry. By combining patterns of registrations in the three registries, we could increase the PPV to 93.1% (95% confidence interval [CI]: 88.5-96.3) and completeness to 88.9% (95% CI: 83.7-92.9), thus creating a national PPGL cohort of 588 patients. PPV for the optimal algorithm was 95.3% (95% CI: 88.5-98.7) in the external validation sample. CONCLUSION: Diagnosis codes for pheochromocytoma had low PPV in several individual health registries. However, with a combination of registries we were able to identify a near-complete national cohort of PPGL patients in Denmark, as a valuable source for epidemiological research.

Androgens and Psychosocial Factors Related to Sexual Dysfunctions in Premenopausal Women∗: ∗2016 ISSM Female Sexual Dysfunction Prize.

INTRODUCTION: The female sexual response is complex and influenced by several biological, psychological, and social factors. Testosterone is believed to modulate a woman's sexual response and desire, because low levels are considered a risk factor for impaired sexual function, but previous studies have been inconclusive. AIM: To investigate how androgen levels and psychosocial factors are associated with female sexual dysfunction (FSD), including hypoactive sexual desire disorder (HSDD). METHODS: The cross-sectional study included 428 premenopausal women 19 to 58 years old who completed a questionnaire on psychosocial factors and had blood sampled at days 6 to 10 in their menstrual cycle. Logistic regression models were built to test the association among hormone levels, psychosocial factors, and sexual end points. MAIN OUTCOME MEASURES: Five different sexual end points were measured using the Female Sexual Function Index and the Female Sexual Distress Scale: impaired sexual function, sexual distress, FSD, low sexual desire, and HSDD. Serum levels of total and free testosterone, androstenedione, dehydroepiandrosterone sulfate, and androsterone glucuronide were analyzed using mass spectrometry. RESULTS: After adjusting for psychosocial factors, women with low sexual desire had significantly lower mean levels of free testosterone and androstenedione compared with women without low sexual desire. None of the androgens were associated with FSD in general or with HSDD in particular. Relationship duration longer than 2 years and mild depressive symptoms increased the risk of having all the sexual end points, including FSD in general and HSDD in particular in multivariate analyses. CONCLUSION: In this large cross-sectional study, low sexual desire was significantly associated with levels of free testosterone and androstenedione, but FSD in general and HSDD in particular were not associated with androgen levels. Length of relationship and depression were associated with FSD including HSDD. Wåhlin-Jacobsen S, Kristensen E, Tønnes Pedersen A, et al. Androgens and Psychosocial Factors Related to Sexual Dysfunctions in Premenopausal Women. J Sex Med 2017;14:366-379.

Female sexual dysfunction: a call to arms for collaboration to understand the sexological elephant.

Female sexual dysfunction (FSD) is a controversial condition, which has prompted much debate regarding its aetiology, components, and even its existence. Our inability to work together as clinicians, psychologists, patients, and advocates hinders our understanding of FSD, and we will only improve matters with increased funding and collaboration.

Testosterone in women--the clinical significance.

Testosterone is an essential hormone for women, with physiological actions mediated directly or via aromatisation to oestradiol throughout the body. Despite the crucial role of testosterone and the high circulating concentrations of this hormone relative to oestradiol in women, studies of its action and the effects of testosterone deficiency and replacement in women are scarce. The primary indication for the prescription of testosterone for women is loss of sexual desire, which causes affected women substantial concern. That no formulation has been approved for this purpose has not impeded the widespread use of testosterone by women--either off-label or as compounded therapy. Observational studies indicate that testosterone has favourable cardiovascular effects measured by surrogate outcomes; however, associations between endogenous testosterone and the risk of cardiovascular disease and total mortality, particularly in older women, are yet to be established. Adverse cardiovascular effects have not been seen in studies of transdermal testosterone therapy in women. Clinical trials suggest that exogenous testosterone enhances cognitive performance and improves musculoskeletal health in postmenopausal women. Unmet needs include the availability of approved testosterone formulations for women and studies to elucidate the contribution of testosterone to cardiovascular, cognitive, and musculoskeletal health and the risk of cancer.

Is there a correlation between androgens and sexual desire in women?

INTRODUCTION: For women, the correlation between circulating androgens and sexual desire is inconclusive. Substitution with androgens at physiological levels improves sexual function in women who experience decreased sexual desire and androgen deficiency from surgical menopause, pituitary disease, and age-related decline in androgen production in the ovaries. Measuring bioactive testosterone is difficult and new methods have been proposed, including measuring the primary androgen metabolite androsterone glucuronide (ADT-G). AIM: The aim of this study was to investigate a possible correlation between serum levels of androgens and sexual desire in women and whether the level of ADT-G is better correlated than the level of circulating androgens with sexual desire. METHODS: This was a cross-sectional study including 560 healthy women aged 19-65 years divided into three age groups. Correlations were considered to be statistically significant at P<0.05. MAIN OUTCOME MEASURE: Sexual desire was determined as the total score of the sexual desire domain of the Female Sexual Function Index. Total testosterone (TT), calculated free testosterone (FT), androstenedione, dehydroepiandrosterone sulfate (DHEAS), and ADT-G were analyzed using mass spectrometry. RESULTS: Sexual desire correlated overall with FT and androstenedione in the total cohort of women. In a subgroup of women aged 25-44 years with no use of systemic hormonal contraception, sexual desire correlated with TT, FT, androstenedione, and DHEAS. In women aged 45-65 years, androstenedione correlated with sexual desire. No correlations between ADT-G and sexual desire were identified. CONCLUSIONS: In the present study, FT and androstenedione were statistically significantly correlated with sexual desire in the total cohort of women. ADT-G did not correlate more strongly than circulating androgens with sexual desire and is therefore not superior to measuring circulating androgens by mass spectrometry.