Comparative study of the neuropeptide-Y sympathetic nerves in endometriotic involved and noninvolved sacrouterine ligaments in women with pelvic endometriosis

STUDY OBJECTIVE: To show the relationship between the neuropeptide-Y pelvic sympathetic nerves and neoangiogenesis in the development of endometriosis DESIGN: Prospective study. SETTING: Academic community teaching hospital. PATIENTS: Fifteen consecutive women with unilateral endometriotic infiltration of the sacrouterine ligaments. INTERVENTIONS: A laparoscopic excision/biopsy of involved and noninvolved parts of the sacrouterine ligaments were taken. The sections were incubated with the neuronal marker rabbit polyclonal anti-protein gene product 9.5 and rabbit polyclonal anti-neuropeptide-Y. We made a comparative study on the distribution of nerve fibers and their relationship to the vessels on intact and endometriotic involved tissue. MEASUREMENTS AND MAIN RESULTS: The results show that a large amount of nerves are present around the blood vessels in the endometriosis samples, and a large number of these nerves are neuropeptide-Y sympathetic nerves. Adrenergic fibers are also present in the intact control subjects, however, in significantly smaller amounts. CONCLUSION: This finding shows a strong relationship between the neuropeptide-Y sympathetic pelvic nerves and the neoangiogenesis required for the development of endometriosis.

Efficacy and Safety of Natalizumab in Crohn’s Disease Patients Treated at 6 Boston Academic Hospitals

BACKGROUND: Despite trials demonstrating its efficacy, many physicians harbor concerns regarding the use of natalizumab in the treatment of patients with refractory Crohn's disease (CD). The purpose of this study was to perform a descriptive analysis of a series of CD patients not currently enrolled in a clinical trial. METHODS: A retrospective case review of patients treated with natalizumab at 6 sites in Massachusetts: Boston Medical Center, Beth Israel Deaconess Medical Center, Brigham & Women's Hospital, Lahey Clinic, Massachusetts General Hospital, and UMass Medical Center. RESULTS: Data on 69 CD patients on natalizumab were collected. At the start of treatment, patients' disease duration was 12 years. A high proportion of patients were women (68%), presented with perianal disease (65%) and upper gastrointestinal tract involvement (14%). Prior nonbiologic therapies were steroids (96%), thiopurines (94%), antibiotics (74%), methotrexate (58%), and at least two anti-tumor necrosis factor agent failures (81%). Sixty-nine percent (44 of 64 patients) with available medical evaluation had a partial or complete clinical response. Loss of response was 13% after an average of 1 year of treatment. Adverse events were infusion reactions, headaches, fever, and infections. No case of progressive multifocal leukoencephalopathy was observed. CONCLUSIONS: In our clinical experience outside the context of a clinical trial, natalizumab is largely reserved for CD patients with extensive ileocolonic disease who have failed conventional immunosuppressants and of at least 2 anti-tumor necrosis factor agents. This drug is, however, well tolerated and offers significant clinical improvement for more than a year in one-third of these difficult-to-treat CD patients.

Risk of Cerebral Venous Thrombosis in Obese Women.

IMPORTANCE Obesity is a risk factor for deep vein thrombosis of the leg and pulmonary embolism. To date, however, whether obesity is associated with adult cerebral venous thrombosis (CVT) has not been assessed. OBJECTIVE To assess whether obesity is a risk factor for CVT. DESIGN, SETTING, AND PARTICIPANTS A case-control study was performed in consecutive adult patients with CVT admitted from July 1, 2006 (Amsterdam), and October 1, 2009 (Berne), through December 31, 2014, to the Academic Medical Center in Amsterdam, the Netherlands, or Inselspital University Hospital in Berne, Switzerland. The control group was composed of individuals from the control population of the Multiple Environmental and Genetic Assessment of Risk Factors for Venous Thrombosis study, which was a large Dutch case-control study performed from March 1, 1999, to September 31, 2004, and in which risk factors for deep vein thrombosis and pulmonary embolism were assessed. Data analysis was performed from January 2 to July 12, 2015. MAIN OUTCOMES AND MEASURES Obesity was determined by body mass index (BMI). A BMI of 30 or greater was considered to indicate obesity, and a BMI of 25 to 29.99 was considered to indicate overweight. A multiple imputation procedure was used for missing data. We adjusted for sex, age, history of cancer, ethnicity, smoking status, and oral contraceptive use. Individuals with normal weight (BMI <25) were the reference category. RESULTS The study included 186 cases and 6134 controls. Cases were younger (median age, 40 vs 48 years), more often female (133 [71.5%] vs 3220 [52.5%]), more often used oral contraceptives (97 [72.9%] vs 758 [23.5%] of women), and more frequently had a history of cancer (17 [9.1%] vs 235 [3.8%]) compared with controls. Obesity (BMI ≥30) was associated with an increased risk of CVT (adjusted odds ratio [OR], 2.63; 95% CI, 1.53-4.54). Stratification by sex revealed a strong association between CVT and obesity in women (adjusted OR, 3.50; 95% CI, 2.00-6.14) but not in men (adjusted OR, 1.16; 95% CI, 0.25-5.30). Further stratification revealed that, in women who used oral contraceptives, overweight and obesity were associated with an increased risk of CVT in a dose-dependent manner (BMI 25.0-29.9: adjusted OR, 11.87; 95% CI, 5.94-23.74; BMI ≥30: adjusted OR, 29.26; 95% CI, 13.47-63.60). No association was found in women who did not use oral contraceptives. CONCLUSIONS AND RELEVANCE Obesity is a strong risk factor for CVT in women who use oral contraceptives.

Publication activities of German junior researchers in academic medicine: which factors impact impact factors?

Previous studies have shown medical students in Germany to have little interest in research while at the same time there is a lack of physician scientists. This study’s aim is to investigate factors influencing publication productivity of physicians during and after finishing their medical doctorate. We conducted a PubMed search for physicians having received their doctoral degree at Ludwig-Maxmilians-University Munich Faculty of Medicine between 2011 and 2013 (N = 924) and identified the appropriate impact factor (IF) for each journal the participants had published in. Gender, age, final grade of the doctorate, participation in a structured doctoral study program and joint publication activities between graduate and academic supervisor were defined as factors. For analyses we used nonparametric procedures. Men show significantly more publications than women. Before their doctoral graduation men publish 1.98 (SD ± 3.64) articles on average, women 1.15 (±2.67) (p < 0.0001, d = 0.27). After completion of the doctorate (up to 06/2015), 40 % of men still publish, while only 24.3 % of women (p < 0.0001, φ = 0.17) continue to publish. No differences were found concerning the value of IFs. Similar results were found regarding the variable ‘participation in a structured doctoral study program’. Until doctoral graduation, program participants publish 2.82 (±5.41) articles, whereas participants doing their doctorate individually only publish 1.39 (±2.87) articles (p < 0.0001, d = 0.46). These differences persist in publication activities after graduation (45.5 vs. 29.7 %, p = 0.008, φ = 0.09). A structured doctorate seems to have positive influence on IFs (4.33 ± 2.91 vs. 3.37 ± 2.82, p = 0.006, d = 0.34). Further significant results concern the variables ‘final grade’ and ‘age’: An early doctoral graduation and an excellent or very good grade for the doctoral thesis positively influence publication productivity. Finally, joint publication activities between the graduate and his/her academic supervisor result in significantly higher IFs (3.64 ± 3.03 vs. 2.84 ± 2.25, p = 0.007, d = 0.28). The study’s results support the assumption about women’s underrepresentation in science as well as the relevance of structured doctoral study programs for preparing and recruiting young academics in medicine for scientific careers. Promoting women and further development of structured doctoral study programs are highly recommended.