Citations

BACKGROUND: Selective serotonin reuptake inhibitor (SSRI) and serotonin–norepinephrine reuptake inhibitor (SNRI) use is known to alter platelet activation and aggregation leading to impairment in hemostasis. Previous studies are ambiguous with regard to bleeding, transfusion, and perioperative complications in patients undergoing cardiac surgery. The purpose of this study was to evaluate the risk of perioperative bleeding, transfusion, morbidity, and mortality in cardiac surgical patients taking SSRI/SNRIs compared with propensity-matched controls. METHODS: Adult patients undergoing cardiac surgery with cardiopulmonary bypass at our institution between January 1, 2004, and December 31, 2014, were eligible for study inclusion. Patients taking SSRI/SNRI medications at the time of surgery were identified and compared against all other patients not taking SSRI/SNRI medications to produce well-matched groups via propensity score analysis. Patients taking SSRI/SNRI medications were matched in a 1:1 ratio to control patients not taking these medications based on an internally estimated propensity score. Primary outcomes included perioperative blood transfusion, chest tube output, and reoperation for bleeding. Secondary outcomes included postoperative complications (renal failure, stroke or transient ischemic accident, prolonged mechanical ventilation, and perioperative myocardial infarction), intensive care unit (ICU) and hospital length of stay (LOS), and 30-day mortality. RESULTS: A total of 1417 pairs of SSRI/SNRI patients and matched controls were retained for analysis. Between SSRI/SNRI patients and matched controls, there was no significant difference in postoperative chest tube output (median, 750.0 vs 750.0 mL; P = .860) or reoperation for bleeding (2.8% vs 2.5%; P = .892). Perioperative transfusion rates across all time points and blood product type were not significantly different between groups, with the overall perioperative transfusion rate for SSRI/SNRI patients 66.5% vs 64.9% for matched controls ( P = .697). Patients in the SSRI/SNRI group had a higher rate of prolonged mechanical ventilation (13.1% vs 8.6%; P = .002), longer ICU LOS (median, 25.5 vs 23.8 hours; P < .001), and longer hospital LOS (median, 6.0 vs 5.0 days; P < .001). Remaining mortality and outcome data were similar between groups. CONCLUSIONS: SSRI/SNRI use was not associated with an increased risk of bleeding or transfusion in patients undergoing cardiac surgery. While there was prolonged mechanical ventilation and increased ICU/hospital LOS in the SSRI/SNRI group, it is unclear that this finding is the result of such medications or rather associated with the underlying psychiatric condition for which they are prescribed. The results of this study suggest that perioperative interruption of SSRI/SNRIs to reduce the risk of perioperative bleeding and transfusion is unwarranted and may risk destabilization of patients’ psychiatric condition.

What is already known about this topic? Lower urinary tract obstruction is associated with high morbidity and mortality. Fetal cystoscopy may allow the correct identification of the etiology of the obstruction and may provide the adequate treatment. What does this study add? Three‐dimensional virtual navigation is a noninvasive approach that provides an immersive virtual reality in the assessment of fetal structures. Three‐dimensional virtual cystoscopy provides a noninvasive evaluation of fetal lower urinary tract obstruction that in the future may help in the selection of candidates for fetal cystoscopy.

Background: Endovascular treatment with mechanical thrombectomy (MT) is beneficial for patients with acute stroke suffering a large-vessel occlusion, although treatment efficacy is highly time-dependent. We hypothesized that interhospital transfer to endovascular-capable centers would result in treatment delays and worse clinical outcomes compared with direct presentation. Methods: STRATIS (Systematic Evaluation of Patients Treated With Neurothrombectomy Devices for Acute Ischemic Stroke) was a prospective, multicenter, observational, single-arm study of real-world MT for acute stroke because of anterior-circulation large-vessel occlusion performed at 55 sites over 2 years, including 1000 patients with severe stroke and treated within 8 hours. Patients underwent MT with or without intravenous tissue plasminogen activator and were admitted to endovascular-capable centers via either interhospital transfer or direct presentation. The primary clinical outcome was functional independence (modified Rankin Score 0–2) at 90 days. We assessed (1) real-world time metrics of stroke care delivery, (2) outcome differences between direct and transfer patients undergoing MT, and (3) the potential impact of local hospital bypass. Results: A total of 984 patients were analyzed. Median onset-to-revascularization time was 202.0 minutes for direct versus 311.5 minutes for transfer patients ( P <0.001). Clinical outcomes were better in the direct group, with 60.0% (299/498) achieving functional independence compared with 52.2% (213/408) in the transfer group (odds ratio, 1.38; 95% confidence interval, 1.06–1.79; P =0.02). Likewise, excellent outcome (modified Rankin Score 0–1) was achieved in 47.4% (236/498) of direct patients versus 38.0% (155/408) of transfer patients (odds ratio, 1.47; 95% confidence interval, 1.13–1.92; P =0.005). Mortality did not differ between the 2 groups (15.1% for direct, 13.7% for transfer; P =0.55). Intravenous tissue plasminogen activator did not impact outcomes. Hypothetical bypass modeling for all transferred patients suggested that intravenous tissue plasminogen activator would be delayed by 12 minutes, but MT would be performed 91 minutes sooner if patients were routed directly to endovascular-capable centers. If bypass is limited to a 20-mile radius from onset, then intravenous tissue plasminogen activator would be delayed by 7 minutes and MT performed 94 minutes earlier. Conclusions: In this large, real-world study, interhospital transfer was associated with significant treatment delays and lower chance of good outcome. Strategies to facilitate more rapid identification of large-vessel occlusion and direct routing to endovascular-capable centers for patients with severe stroke may improve outcomes. Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT02239640.

Abstract Cancer has been considered a heterogeneous disease, which mainly arises from the accumulation of genetic mutations, leading to a loss of tumor suppressor genes, as well as to an activation of oncogenes. The epigenetic mechanisms, such as DNA and histone modifications, are processes that regulate gene expression, and an alteration of these can contribute to cancer progression. Methylation on histone 3 lysine 9 (H3K9), in particular di-methyl (H3K9me2), is mainly mediated by the nuclear histone lysine methyltransferase G9a. Preliminary data showed that G9a was overexpressed in aggressive and highly metastatic forms of cancer. However, to date, this pathway has remained unstudied in esophageal adenocarcinoma. Interestingly, epigenetic drugs, such as those that target G9a, have the potential to reverse the adverse effects acquired downstream from genetic mutations, which currently cannot be directly repaired or targeted. In the current study, we utilize BRD4770, an S-adenosylmethionine (SAM) mimetic inhibitor of G9a, to determine the benefits of inhibiting this pathway in the context of esophageal adenocarcinoma. We hypothesize that pharmacological targeting of G9a by BRD4770 inhibits esophageal adenocarcinoma cell growth. To examine G9a-mediated dimethyl histone H3K9 levels in esophageal adenocarcinoma, we performed immunohistochemistry on paraffin-embedded esophageal adenocarcinoma tissues with an H3K9me2 antibody. In order to confirm specificity of BRD4770 in regulating the dimethyl histone H3K9 levels, and thus trimethyl H3K9 levels, in esophageal adenocarcinoma, we treated human esophageal adenocarcinoma cells (SKGT-4) with different doses of BRD4770 at various time points for western blot analysis using antibodies against histone H3K9me2 and H3K9me3. Moreover, we found that treatment of SKGT-4 cells with BRD4770 significantly inhibits cell proliferation by MTS assay, as well as clonogenic survival. Therefore, to determine the mechanism(s) by which BRD4770 inhibits the growth of esophageal adenocarcinoma cells, we utilized Caspase-3, Senescence, and Autophagy Assays. Our data shows that inhibition of G9a by BRD4770 does not induce Caspase 3 activity, while it significantly increases senescence and autophagy. Combined, our results suggest that BRD4770 has an important pharmacological role in regulating methyl histone H3K9 levels that may lead to inhibition of esophageal adenocarcinoma cell growth via an increase in senescence and autophagy. Further studies are focused on in vivo models to understand these effects in more detail, however the fact that an anti-G9a drug antagonizes esophageal adenocarcinoma cell growth raises optimism for its potential in the treatment of this malignancy. Note: This abstract was not presented at the meeting. Citation Format: Mabel G. Perez-Oquendo, Gwen A. Lomberk, Raul A. Urrutia, Sarah Kossak, Navtej Buttar, Sounak Gupta. Treatment with the G9a antagonist, BRD4770, inhibits esophageal adenocarcinoma cell growth [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr LB-094. doi:10.1158/1538-7445.AM2017-LB-094

ObjectiveTo confirm prior findings that the larger the maximum monthly increase in solar insolation in springtime, the younger the age of onset of bipolar disorder.MethodData were collected from 5536 patients at 50 sites in 32 countries on six continents. Onset occurred at 456 locations in 57 countries. Variables included solar insolation, birth‐cohort, family history, polarity of first episode and country physician density.ResultsThere was a significant, inverse association between the maximum monthly increase in solar insolation at the onset location, and the age of onset. This effect was reduced in those without a family history of mood disorders and with a first episode of mania rather than depression. The maximum monthly increase occurred in springtime. The youngest birth‐cohort had the youngest age of onset. All prior relationships were confirmed using both the entire sample, and only the youngest birth‐cohort (all estimated coefficientsP< 0.001).ConclusionA large increase in springtime solar insolation may impact the onset of bipolar disorder, especially with a family history of mood disorders. Recent societal changes that affect light exposure (LEDlighting, mobile devices backlit withLEDs) may influence adaptability to a springtime circadian challenge.