SAT-038 Ambulatory Blood Pressure Increases in Hypogonadal Men Who Develop Increases in Hematocrit on Oral Testosterone Undecanoate

There is concern that testosterone replacement therapies might increase blood pressure (BP) with chronic use. Testosterone undecanoate is a novel oral testosterone therapy under development for the treatment of male hypogonadism. We studied the effects of testosterone undecanoate (225 mg twice daily) on ambulatory blood pressure (ABP) and heart rate, in 138 men with hypogonadism (mean age, 54 years, 79% white, 48% with a history of hypertension). Ambulatory BP and heart rate and hematologic parameters were obtained at baseline and following 4 months of daily therapy. Changes from baseline in ambulatory 24-hour, awake, and sleep systolic BP of 3.8 (p=0.06), 5.2 (p=0.01), and 4.3 mmHg (p=0.07) were observed post-treatment, respectively. Smaller changes in the diastolic BP were observed (1.2 (p=0.13), 1.7 (p=0.04), and 1.7 mmHg (p=0.11) for 24-hour, awake, and sleep, respectively). Changes in the 24-hour, awake and sleep heart rates were 1.9 (p=0.07), 2.6 (p=0.02), and 0.4 (p=0.68) beats/minute respectively. There were no significant differences in changes from baseline in the 24-hour ambulatory BP for the 57 subjects who had a medical history of hypertension versus the 61 subjects who did not have hypertension: 4.5/1.5 mmHg in the hypertension subgroup versus 3.2/0.9 mmHg in the non-hypertensive subgroup (p = 0.53/0.46 between groups). Hematocrit and hemoglobin increased by 3.2% and 0.9 g/dl in all subjects after 4 months of therapy. In those men in the top quartile of changes in hematocrit (corresponding to upper / lower boundary increases of 6 and 14% with 9.3% achieving levels > 52%), the largest increases in ambulatory systolic BP (8.3 mmHg) were observed, whereas the changes in ambulatory systolic BP in the lower 3 quartiles were substantially smaller (1.6, 3.2, and 2.7 mmHg in quartiles 1, 2 and 3 of hematocrit change, respectively). In conclusion, these data demonstrate increases in ambulatory BP occurred following 4 months of oral testosterone undecanoate, particularly in those men whose hematocrit rose by > 6% or whose resultant hematocrit was 52% or higher. Hence, hematocrit maybe a useful clinical parameter that could effectively predict the risk of developing increases in BP on oral testosterone undecanoate.

Genetic analyses identify widespread sex-differential participation bias

Genetic association results are often interpreted with the assumption that study participation does not affect downstream analyses. Understanding the genetic basis of this participation bias is challenging as it requires the genotypes of unseen individuals. However, we demonstrate that it is possible to estimate comparative biases by performing GWAS contrasting one subgroup versus another. For example, we show that sex exhibits autosomal heritability in the presence of sex-differential participation bias. By performing a GWAS of sex in ∼3.3 million males and females, we identify over 150 autosomal loci significantly associated with sex and highlight complex traits underpinning differences in study participation between sexes. For example, the body mass index (BMI) increasing allele at the FTO locus was observed at higher frequency in males compared to females (OR 1.02 [1.02-1.03], P=4.4×10-36). Finally, we demonstrate how these biases can potentially lead to incorrect inferences in downstream analyses and propose a conceptual framework for addressing such biases. Our findings highlight a new challenge that genetic studies may face as sample sizes continue to grow.

Pancreatic neck thickness: A possible key to stump closure technique selection after distal pancreatectomy

Background To date, no stump closure technique has been shown to be superior in lowering the risk of postoperative pancreatic fistula (POPF) after pancreatectomy. The aims our study were to investigate the possibility to influence POPF risk by selection of stump closure technique according to pancreatic parenchyma thickness and to establish a thickness cut-off value for selection of a hand-sewn and stapled closure technique. Methods A retrospective analysis of consecutive patients who underwent distal pancreatectomy at a single centre was performed. Anatomical determination of the transection site (pancreatic neck, body, or tail) was based on operative report and postoperative follow-up computed tomography (CT), with the thickness measured on the most recent CT image before surgery. Patients were classified by the thickness of the transection site, and sub-classified according to stump closure technique. POPF incidence, morbidity, mortality, and baseline-characteristics were investigated between groups. Results Among the 115 cases included in the analysis, the incidence of POPF was 33%, with no difference between stapled (29.9%) and hand-sewn (37.5%) closure techniques (p=0.426), regardless of transection site thickness. Among those with a transection site <13 mm, the incidence of POPF was 4.6% in the stapler subgroup versus 45.5% in the hand-sewn subgroup (p=0.0002). Among patients with a transection site ≥13 mm, the incidence of POPF was 75% in the stapler subgroup versus 30.8% in the hand-sewn subgroup (p=0.007). Conclusions Transection in the pancreatic neck, stapler closure of thin parenchyma, and hand-sewn closure of thick parenchyma were associated with significantly lower risk of POPF.

Emotional processing in panic disorder and its subtypes: An fMRI study using the emotional faces paradigm

IntroductionThe literature on the neurobiology of emotional processing in panic disorder (PD) remains inconsistent. Clinical heterogeneity could be causing this.ObjectiveTo investigate differences in brain activity between PD and healthy controls using the emotional faces fMRI paradigm.AimsTo elucidate neurobiological mechanisms underlying emotional processing in PD and previously identified subtypes (Pattyn et al., 2015).MethodsThe main analysis compared the neural processing of different emotional facial expressions from a large group of PD patients (n = 73) versus healthy controls (n = 58) originating from the Netherlands Study of Depression and Anxiety (NESDA). A second analysis divided the PD group into the three previously identified subgroups: a cognitive-autonomic (n = 22), an autonomic (n = 16) and an aspecific subgroup (n = 35). The fusiform gyrus, the anterior cingulate cortex and the insula were used in a ROI approach.ResultsComparing PD patients with healthy controls, a decreased activity on angry faces was observed in the left fusiform gyrus. The subgroup analysis showed more activity in the anterior cingulate cortex on neutral faces in the cognitive-autonomic subgroup versus the autonomic subgroup and a decreased activity in the left fusiform gyrus on angry faces compared to the aspecific subgroup. Less activity was observed in the right insula on neutral faces in the autonomic subgroup versus the aspecific subgroup.ConclusionReduced activity in the left fusiform gyrus was differentiating panic disorder patients from healthy controls. In accordance with clinical subtyping, between-subtype differences are an indication that a phenomenological approach could provide more insight in underlying neurobiological mechanisms in emotional processing in PD.Disclosure of interestThe authors have not supplied their declaration of competing interest.