Long-Term Effects of Gonadotropin-Releasing Hormone Agonists and Add-Back in Adolescent Endometriosis

Study Objective

To explore the potential occurrence of long-term side effects and tolerability of gonadotropin-releasing hormone agonist (GnRHa) plus 2 different add-back regimens in adolescent patients with endometriosis.

Collective cell migration of the nephric duct requires FGF signaling

Background : During the course of development, the vertebrate nephric duct (ND) extends and migrates from the place of its initial formation, adjacent to the anterior somites, until it inserts into the bladder or cloaca in the posterior region of the embryo. The molecular mechanisms that guide ND migration are poorly understood. Results : A novel Gata3‐enhancer‐Gfp‐based chick embryo live imaging system was developed that permits documentation of ND migration at the individual cell level for the first time. FGF Receptors and FGF response genes are expressed in the ND, and FGF ligands are expressed in surrounding tissues. FGF receptor inhibition blocked nephric duct migration. Individual inhibitors of the Erk, p38, or Jnk pathways did not affect duct migration, but inhibition of all three pathways together did inhibit migration of the duct. A localized source of FGF8 placed adjacent to the nephric duct did not affect the duct migration path. Conclusions : FGF signaling acts as a “motor” that is required for duct migration, but other signals are needed to determine the directionality of the duct migration pathway. Developmental Dynamics 244:157–167, 2015. © 2014 Wiley Periodicals, Inc.     

Whole‐exome sequencing defines the mutational landscape of pheochromocytoma and identifies KMT2D as a recurrently mutated gene

As subsets of pheochromocytomas (PCCs) lack a defined molecular etiology, we sought to characterize the mutational landscape of PCCs to identify novel gene candidates involved in disease development. A discovery cohort of 15 PCCs wild type for mutations in PCC susceptibility genes underwent whole‐exome sequencing, and an additional 83 PCCs served as a verification cohort for targeted sequencing of candidate mutations. A low rate of nonsilent single nucleotide variants (SNVs) was detected (6.1/sample). Somatic HRAS and EPAS1 mutations were observed in one case each, whereas the remaining 13 cases did not exhibit variants in established PCC genes. SNVs aggregated in apoptosis‐related pathways, and mutations in COSMIC genes not previously reported in PCCs included ZAN, MITF, WDTC1, and CAMTA1. Two somatic mutations and one constitutional variant in the well‐established cancer gene lysine (K)‐specific methyltransferase 2D (KMT2D, MLL2) were discovered in one sample each, prompting KMT2D screening using focused exome‐sequencing in the verification cohort. An additional 11 PCCs displayed KMT2D variants, of which two were recurrent. In total, missense KMT2D variants were found in 14 (11 somatic, two constitutional, one undetermined) of 99 PCCs (14%). Five cases displayed somatic mutations in the functional FYR/SET domains of KMT2D, constituting 36% of all KMT2D‐mutated PCCs. KMT2D expression was upregulated in PCCs compared to normal adrenals, and KMT2D overexpression positively affected cell migration in a PCC cell line. We conclude that KMT2D represents a recurrently mutated gene with potential implication for PCC development. © 2015 The Authors. Genes, Chromosomes & Cancer Published by Wiley Periodicals, Inc.     

PSTPIP1‐associated myeloid‐related proteinemia inflammatory syndrome: A rare cause of childhood neutropenia associated with systemic inflammation and hyperzincemia

Neutropenia in pediatric patients can be due to a variety of disorders. We describe two patients who underwent extensive evaluation over many years for arthralgias and moderate neutropenia of unclear etiology. Genetic testing identified a pathogenic variant in PSTPIP1 (proline‐serine‐threonine phosphatase‐interacting protein 1) in both patients. Markedly elevated inflammatory markers and zinc levels confirmed the rare diagnosis of PSTPIP1‐associated myeloid‐related proteinemia inflammatory (PAMI) syndrome, tailoring treatment. Neutropenia is common in patients with PAMI syndrome. Unique mutations seen in PAMI syndrome may account for the specific phenotypic features of this disorder.     

Study of discharge communications from hospital doctors to an inner London general practice

In inner London patients are now being discharged from hospital earlier to be cared for by the community services. In this study the general practitioners in one inner London practice were asked to evaluate discharge communications from hospital doctors. The general practitioners were dissatisfied with the delay in receiving over one third of the letters and with the content of almost a fifth. They also felt that delay and lack of detail affected their management in 24% of cases. They would have liked more information in the letters, particularly about drug regimens. Some suggestions for improvement in written discharge communications are made.     

Adolescent–Parent Dyadic Retention in an Interview Study and Changes in Willingness to Participate in a Hypothetical Microbicide Safety Study

Study Objective

In this study we describe adolescent and parent retention and changes in willingness to participate (WTP) in research among adolescents, parents, and adolescent–parent dyads.

Birth plans—Impact on mode of delivery,obstetrical interventions,and birth experience satisfaction: A prospective cohort study

Objective

To examine whether the presence of a birth plan was associated with mode of delivery, obstetrical interventions, and patient satisfaction.

Methods

This was a prospective cohort study of singleton pregnancies greater than 34 weeks’ gestation powered to evaluate a difference in mode of delivery. Maternal characteristics, antenatal factors, neonatal characteristics, and patient satisfaction measures were compared between groups. Differences between groups were analyzed using chi‐squared for categorical variables, Fisher exact test for dichotomous variables, and Wilcoxon rank sum test for continuous or ordinal variables.

Results

Three hundred women were recruited: 143 (48%) had a birth plan. There was no significant difference in the risk of cesarean delivery for women with a birth plan compared with those without a birth plan (21% vs 16%, adjusted odds ratio [adjOR] 1.11 [95% confidence interval (CI) 0.61‐2.04]). Women with a birth plan were 28% less likely to receive oxytocin (P < .01), 29% less likely to undergo artificial rupture of membranes (P < .01), and 31% less likely to have an epidural (P < .01). There was no difference in the length of labor (P = .12). Women with a birth plan were less satisfied (P < .01) and felt less in control (P < .01) of their birth experience than those without a birth plan.

Conclusion

Women with and without a birth plan had similar odds of cesarean delivery. Though they had fewer obstetrical interventions, they were less satisfied with their birth experience, compared with women without birth plans. Further research is needed to understand how to improve childbirth‐related patient satisfaction.     

Genetic correction of PSA values using sequence variants associated with PSA levels

Measuring serum levels of the prostate-specific antigen (PSA) is the most common screening method for prostate cancer. However, PSA levels are affected by a number of factors apart from neoplasia. Notably, around 40% of the variability of PSA levels in the general population is accounted for by inherited factors, suggesting that it may be possible to improve both sensitivity and specificity by adjusting test results for genetic effects. To search for sequence variants that associate with PSA levels, we performed a genome-wide association study and follow-up analysis using PSA information from 15,757 Icelandic and 454 British men not diagnosed with prostate cancer. Overall, we detected a genome-wide significant association between PSA levels and single-nucleotide polymorphisms (SNPs) at six loci: 5p15.33 (rs2736098), 10q11 (rs10993994), 10q26 (rs10788160), 12q24 (rs11067228), 17q12 (rs4430796), and 19q13.33 [rs17632542 (KLK3: I179T)], each with P(combined) <3 × 10(-10). Among 3834 men who underwent a biopsy of the prostate, the 10q26, 12q24, and 19q13.33 alleles that associate with high PSA levels are associated with higher probability of a negative biopsy (odds ratio between 1.15 and 1.27). Assessment of association between the six loci and prostate cancer risk in 5325 cases and 41,417 controls from Iceland, the Netherlands, Spain, Romania, and the United States showed that the SNPs at 10q26 and 12q24 were exclusively associated with PSA levels, whereas the other four loci also were associated with prostate cancer risk. We propose that a personalized PSA cutoff value, based on genotype, should be used when deciding to perform a prostate biopsy.     

Outcome analysis of cervical adenosquamous carcinoma compared with adenocarcinoma

Objective. To compare survival between patients with cervical adenocarcinoma (AC) and adenosquamous carcinoma (ASC). Design. Retrospective study. Setting. National Taiwan University Hospital, Taipei, Taiwan. Population. All patients with cervical AC or ASC who received definitive treatment from January 1995 to December 2009. Methods. Medical and histopathological record review. Main outcome measures. Overall and recurrence-free survival. Results. A total of 170 women received a histological diagnosis of AC and 42 of ASC. The median follow-up was 56.7 months. There were no significant differences in age, International Federation of Gynecology and Obstetrics (FIGO) stage, gravidity or treatment modality between women with AC and ASC. Patients with ASC had a higher percentage of poorly differentiated tumors than those with AC (33.3 vs. 15.3%, respectively; p= 0.014). Five year overall and recurrence-free survival was 66.8 and 58.9%, respectively, for women with AC and 69.5 and 61.9%, respectively, for those with ASC (p= 0.795 and p= 0.892, respectively). Survival outcomes in patients with early or advanced stage disease did not differ between the histological groups. No differences in failure patterns were found between the two groups. The FIGO stage and treatment modality were factors which affected overall and recurrence-free survival. Conclusions. We did not find evidence to suggest that ASC subtypes indicate worse outcome. Cervical ASC could be categorized as one subtype of AC. The FIGO stage and treatment modalities have greater influence on outcomes than histological subtype.     

Physical activity of young children: a two-year follow-up

Inadequate physical activity in children is a major health concern. The purpose of this study was to examine changes in physical activity of boys and girls, between 6-8 and 8-10 years of age and how activity patterns correlated with selected family, child, and environment factors. The sample included 59 children without motor delays (26 boys and 23 girls) between 8 and 10 years of age. Twenty-two of the children participated in a previous study at 6-8 years of age. Parents completed a questionnaire on their children's non-physical and physical activities. Children wore a pedometer during two weekdays and two weekend days. The results indicate that girls spent more time on homework and reading and on crafts and indoor play than boys. Girls spent more time on musical and cultural activities and boys spent more time on screen-based activities at 8-10 years of age. Children spent significantly less time on physical activity at 8-10 years of age. Boys took more steps per day than girls on weekends. The average number of steps taken per weekday increased for boys, but not girls, at 8-10 years of age. There was an inverse relationship between body mass index and number of steps taken per day (weekdays r = -.28; weekend r = -.32). Socioeconomic status was associated with the number of steps taken by children on weekends (r = .34). The results have implications for physical activities for girls and school and community programs for children.