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Background Diffuse intrinsic pontine glioma (DIPG) remains a clinico-radiologic diagnosis without routine tissue acquisition. Reliable imaging distinction between DIPG and other pontine tumors with potentially more favorable prognoses and treatment considerations is essential. Methods Cases submitted to the International DIPG registry (IDIPGR) with histopathologic and/or radiologic data were analyzed. Central imaging review was performed on diagnostic brain MRIs (if available) by two neuro-radiologists. Imaging features suggestive of alternative diagnoses included nonpontine origin, Results Among 286 patients with pathology from biopsy and/or autopsy, 23 (8%) had histologic diagnoses inconsistent with DIPG, most commonly nondiffuse low-grade gliomas and embryonal tumors. Among 569 patients with centrally-reviewed diagnostic MRIs, 40 (7%) were classified as non-DIPG, alternative diagnosis suspected. The combined analysis included 151 patients with both histopathology and centrally-reviewed MRI. Of 77 patients with imaging classified as characteristic of DIPG, 76 (99%) had histopathologic diagnoses consistent with DIPG (infiltrating grade II-IV gliomas). Of 57 patients classified as likely DIPG with some unusual imaging features, 55 (96%) had histopathologic diagnoses consistent with DIPG. Of 17 patients with imaging features suggestive of an alternative diagnosis, eight (47%) had histopathologic diagnoses inconsistent with DIPG (remaining patients were excluded due to nonpontine tumor origin). Association between central neuro-imaging review impression and histopathology was significant (p < 0.001), and central neuro-imaging impression was prognostic of overall survival. Conclusions The accuracy and important role of central neuro-imaging review in confirming the diagnosis of DIPG is demonstrated.

Summary Background The addition of cisplatin or cetuximab to radiotherapy in patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN) has significantly improved the outcome. While the superiority of cisplatin over cetuximab in combination with radiotherapy has been shown in a definitive setting, we set out to compare postoperative chemoradiotherapy with cisplatin to radioimmunotherapy with cetuximab and radiotherapy alone within the Austrian head and neck cancer registry of the Working Group on Pharmaceutical Tumor Treatment (AGMT) study group. Material and methods In the AGMT head and neck cancer registry, data of 557 patients with SCCHN from five Austrian cancer centers were prospectively collected between 2012 and 2017. Of these patients 120 received postoperative chemoradiotherapy with cisplatin, 26 patients received postoperative radioimmunotherapy with cetuximab and 56 patients were treated with adjuvant radiotherapy only. Patient characteristics, stage of disease, details on treatment as well as survival were analyzed by a chart-based review. Results In patients treated with postoperative radiotherapy the addition of cisplatin significantly improved progression-free survival (PFS) and overall survival (OS) compared to cetuximab (PFS 84.2 months vs. 17.0 months, p = 0.04, OS not reached vs. 46.0 months, p = 0.02) and PFS compared to radiotherapy alone (PFS 84.2 months vs. 28.5 months, p Conclusion This study confirmed the importance of multimodal treatment concepts in patients with locally advanced SCCHN. Postoperative cetuximab might be an option in patients not eligible for high-dose cisplatin but cisplatin should remain the standard of care.

Open-angle glaucomas are a group of chronic progressive optic nerve neuropathies with a gonioscopic open anterior chamber angle. They are one of the main causes of visual impairment and blindness in industrialized countries. The aim of this article is to discuss and evaluate the epidemiology and risk factors for the development of open-angle glaucoma and to present the screening procedure for open-angle glaucoma according to the recently published S2e guidelines of the Association of the Scientific Medical Societies in Germany (AWMF).

Background and importance Dural arteriovenous fistulas (dAVFs) are vascular abnormalities of the central nervous system that can cause a wide array of neurological dysfunction depending on their location, flow, and propensity to rupture. Symptomatic dAVFs at the cranio-cervical junction usually result in hemorrhage or cervical myelopathy. Distantly located dAVFs of the foramen magnum are a rare cause of thoracic intrinsic myelopathy. Clinical presentation An 83-yr-old man presented with progressive lower extremity weakness, numbness, and difficulty walking along with episodes of bowel incontinence. Magnetic resonance imaging of the cervical spine demonstrated multilevel cervical disc disease with stenosis and longitudinal cervical cord signal change extending into the upper thoracic spinal cord. Cerebral and spinal angiography revealed a dAVF in the lateral foramen magnum region. Given the location, feeding vasculature, and morphology of the fistula, endovascular embolization was not attempted. Microsurgical resection with confirmative indocyanine green fluorescent imaging was performed with adequate obliteration of the fistula. The patient's neurological baseline was preserved postoperatively with improvement of lower extremity numbness. Conclusion We present a brief overview of this neuropathologic entity and demonstrate microsurgical resection of a foramen magnum dAVF through operative video. Craniocervical dAVFs should remain on the differential diagnosis of patients presenting with progressive thoracolumbar myelopathy.

To determine the impact of prior vaginal birth on neonatal and maternal outcomes among individuals undergoing a trial of labor after two cesarean births.This was a cross-sectional study using the U.S. National Vital Statistics 2014-2018 period linked birth and infant death data. Inclusion criteria were term, cephalic, singleton pregnancies with two prior cesarean births. The primary exposure variable was a trial of labor after cesarean vs prelabor repeat cesarean birth. Cohorts were defined by the presence or absence of a prior vaginal birth. The primary outcome was a composite of adverse neonatal outcomes (Apgar score5 at 5 min, assisted ventilation6 h, neonatal seizures, or neonatal death within 27 days). Secondary outcomes included a maternal composite and the cesarean birth rate. Propensity score matching was used to account for baseline differences in treatment allocation within each cohort, and conditional logistic regression assessed the association between the exposure and outcomes.The composite neonatal adverse outcome was significantly higher in those undergoing a trial of labor after cesarean compared to prelabor repeat cesarean birth in both individuals without a prior vaginal birth (8.2 vs 11.6 per 1000 live births, OR 1.41; 95% CI 1.12-1.70) and with a prior vaginal birth (9.6 vs 12.4 per 1000 live births, OR 1.30; 95% CI 1.08-1.57). The composite maternal adverse outcome was significantly higher among individuals without a prior vaginal birth undergoing trial of labor after cesarean (6.0 vs 9.5 per 1000 live births, OR 1.59; 95% CI 1.26-2.09), but was similar in those with a prior vaginal birth (7.9 vs 9.3 per 1000 live births, OR 1.18; 95% CI 0.97-1.46).In individuals with two prior cesarean births, trial of labor after cesarean was associated with increased neonatal adverse outcomes when compared to prelabor repeat cesarean birth, irrespective of a history of vaginal birth. In individuals with a prior vaginal birth, the composite maternal adverse outcome was not elevated in the trial of labor cohort.

Aims Free fatty acid receptor 4 (Ffar4) is a G-protein-coupled receptor for endogenous medium-/long-chain fatty acids that attenuates metabolic disease and inflammation. However, the function of Ffar4 in the heart is unclear. Given its putative beneficial role, we hypothesized that Ffar4 would protect the heart from pathologic stress. Methods and results In mice lacking Ffar4 (Ffar4KO), we found that Ffar4 is required for an adaptive response to pressure overload induced by transverse aortic constriction (TAC), identifying a novel cardioprotective function for Ffar4. Following TAC, remodelling was worsened in Ffar4KO hearts, with greater hypertrophy and contractile dysfunction. Transcriptome analysis 3-day post-TAC identified transcriptional deficits in genes associated with cytoplasmic phospholipase A2α signalling and oxylipin synthesis and the reduction of oxidative stress in Ffar4KO myocytes. In cultured adult cardiac myocytes, Ffar4 induced the production of the eicosapentaenoic acid (EPA)-derived, pro-resolving oxylipin 18-hydroxyeicosapentaenoic acid (18-HEPE). Furthermore, the activation of Ffar4 attenuated cardiac myocyte death from oxidative stress, while 18-HEPE rescued Ffar4KO myocytes. Systemically, Ffar4 maintained pro-resolving oxylipins and attenuated autoxidation basally, and increased pro-inflammatory and pro-resolving oxylipins, including 18-HEPE, in high-density lipoproteins post-TAC. In humans, Ffar4 expression decreased in heart failure, while the signalling-deficient Ffar4 R270H polymorphism correlated with eccentric remodelling in a large clinical cohort paralleling changes observed in Ffar4KO mice post-TAC. Conclusion Our data indicate that Ffar4 in cardiac myocytes responds to endogenous fatty acids, reducing oxidative injury, and protecting the heart from pathologic stress, with significant translational implications for targeting Ffar4 in cardiovascular disease.

Self-monitoring of blood pressure (BP) and using text messages to communicate values with health care providers may be a viable alternative to in-person visits to obtain postpartum BP measurements. This study was conducted to understand perspectives of nurses and physicians who have used text-based postpartum BP monitoring. Nurses and physicians who implemented text-based postpartum BP monitoring programs participated in a survey focused on perceived quality and an interview focused on perceived program advantages, disadvantages, and implementation considerations. Participants (n = 5) report that these methods are safe and ease the burden of obtaining high-quality care for this high-risk vulnerable population.

Intractable epilepsy impacts many children. Surgically resective and palliative treatments have developed to increase seizure freedom or palliate the seizure burden in those with medically refractory epilepsy. However, surgical epilepsy treatment can confer significant morbidity and death. Endoscope-assisted surgical approaches may be helpful in reducing the morbidity related to traditional open surgical approaches while allowing for good visualization of surgical targets. Here, the authors report a case utilizing an endoscope-assisted keyhole approach to perform a posterior quadrantectomy and corpus callosotomy, achieving the surgical goals of disconnection and reducing the need for large craniotomy exposure. They present the case of a 17-year-old male with medically refractory epilepsy treated with endoscope-assisted posterior quadrantectomy and corpus callosotomy through two mini-craniotomies to achieve a functional disconnection. To the authors’ knowledge, this is the first reported case of an endoscope-assisted approach for a posterior quadrantectomy for surgical epilepsy treatment in an adult or a pediatric patient. The case is reported to highlight the technical nuances and benefits of this approach in select patients as well as the expansion of applications of endoscope-assisted epilepsy surgery.

Offenwinkelglaukome sind eine Gruppe chronisch progredienter Optikusneuropathien mit gonioskopisch offenem Kammerwinkel. Sie stellen eine der Hauptursachen fur Sehbehinderung und Blindheit in den Industrielandern dar. Im Rahmen dieses Beitrags sollen Epidemiologie und Risikofaktoren fur das Auftreten des Offenwinkelglaukoms diskutiert und bewertet werden sowie das Vorgehen bei der Fruherkennung eines Offenwinkelglaukoms gemas der kurzlich erschienen S2e-Leitlinie der Arbeitsgemeinschaft der Wissenschaftlichen Fachgesellschaften (AWMF) vorgestellt werden.

Urologic tumors make up approximately 10% of all pediatric cancers, and include a variety of different histologies and imaging considerations. In this review, we discuss standard radiologic approaches for children with tumors arising in the genitourinary system, and identify important ways in which imaging affects the differential diagnosis, preoperative planning, and staging of these tumors. In addition, we provide an update on strategies to reduce the time of imaging, which may obviate the need for sedation in younger patients. Efforts to reduce a patient's overall radiation exposure and subsequent risk of second malignancy are also detailed, including recent work on surveillance imaging following completion of therapy. Finally, we highlight new techniques such as radiomics that are now being investigated for patients with these malignancies.

IntroductionHemorrhage is the leading cause of preventable death on the battlefield, and hemostasis is particularly challenging to achieve at junctional sites such as the axillary or inguinal regions. Mission-oriented protective posture (MOPP) gear, as worn most recently in Syria to guard against chemical weapons, can make the performance of technical skills more challenging still. The objective of this study was to evaluate how wearing MOPP gear affects the application time of the SAM Medical Junctional Tourniquet (SJT) by U.S. Army combat medics.Materials and MethodsWe conducted a prospective, randomized control trial evaluating time for SJT application between participants wearing MOPP versus those not wearing MOPP. Secondary outcomes included SJT application success rate and participant appraisal of SJT application difficulty assessed with five-point Likert items, between groups. Participants placed SJTs on robotic simulation mannequins with a penetrating inguinal injury.ResultsIn April 2019, we enrolled 49 combat medics. Most participants were male (77.5%), had a median age of 25 (interquartile range 23–28), and in the grade of E4 or less (63.3%). Mean SJT application times in seconds were higher among those wearing MOPP versus those who were not (223.1 versus 167.2; 95% confidence interval for difference in means 5.293, 106.374; P = 0.03). Participants wearing MOPP had a less successful application rate overall, but this difference was not statistically significant (64.3% versus 81.0%, P = 0.34). Compared to participants not wearing MOPP, those wearing MOPP agreed that SJT application was difficult (4 versus 3, P = 0.03), what they were wearing affected SJT application (4 versus 2, P = 0.01), and it was difficult to use their hands during SJT application (4 versus 1, P ConclusionsWearing military MOPP gear significantly prolongs the amount of time required for combat medics to apply an SJT on a simulated casualty with a penetrating inguinal injury. This study highlights the importance of incorporating MOPP gear into medical training scenarios to improve skills competency while wearing these protective garments.

ZusammenfassungDie COVID-19-Pandemie stellt derzeit weltweit eine Herausforderung dar. In Österreich konnte eine Krise innerhalb des medizinischen Versorgungssystems bisher verhindert werden. Die Behandlung von Patienten mit ambulant erworbener Pneumonie („community acquired pneumonia“, CAP), inklusive durch SARS-CoV-2-Infektionen, sollte sich auch während der Pandemie weiterhin an evidenzbasierten CAP-Leitlinien orientieren. COVID-19-spezifische Anpassungen sind jedoch sinnvoll. Die Behandlung von Patienten mit chronischen Lungenerkrankungen muss während der Pandemie angepasst werden, ist aber weiterhin zu gewährleisten.

Maternal depression is a risk factor for the development of problem behavior in children. Although food insecurity and housing instability are associated with adult depression and child behavior, how these economic factors mediate or moderate the relationship between maternal depression and child problem behavior is not understood. The purpose of this study was to determine whether food insecurity and housing instability are mediators and/or moderators of the relationship between maternal depression when children are age 3 and children's problem behaviors at age 9 and to determine whether these mechanisms differ by race/ethnicity. We used data from the Fragile Families and Child Wellbeing Study. Food insecurity and housing instability at age 5 were tested as potential mediators and moderators of the relationship between maternal depression status at age 3 and problem behavior at age 9. A path analysis confirmed our hypothesis that food insecurity and housing instability partially mediate the relationship between maternal depression when children are age 3 and problem behavior at age 9. However, housing instability was only a mediator for externalizing problem behavior and not internalizing problem behavior or overall problem behavior. Results of the moderation analysis suggest that neither food insecurity nor housing instability were moderators. None of the mechanisms explored differed by race/ethnicity. While our findings stress the continued need for interventions that address child food insecurity, they emphasize the importance of interventions that address maternal mental health throughout a child's life. Given the central role of maternal health in child development, additional efforts should be made to target maternal depression.

1. Claci A. Walls* 2. W. Jackson Smith, MD† 3. John M. Draus, MD‡ 4. Lars M. Wagner, MD§ 1. *University of Kentucky College of Medicine, Lexington, KY 2. †Division of Pediatric Endocrinology, 3. ‡Division of Pediatric Surgery, and 4. §Division of Pediatric Hematology/Oncology, University of Kentucky College of Medicine, Lexington, KY A 15-year-old boy is evaluated for gynecomastia that has continued to increase in size and discomfort during the past year. In addition, he also has moderate to severe acne that has not improved with topical therapies and systemic antibiotic drugs. He reports having some general fatigue as well as increased appetite, and he has gained 13 lb (5.9 kg) in the previous 7 months. There has been no fever, and apart from occasional headaches, he has no other complaints of pain. His personal and family medical history is otherwise normal. His only medications are minocycline and topical isotretinoin and clindamycin to treat his acne. On physical examination the blood pressure is 156/98 mm Hg. He has extensive acne on his face, upper chest, and back. Examination of the breasts shows bilateral and mildly tender gynecomastia, with fibroglandular tissue measuring 10 cm in the right breast and 9 cm in the left, and both having secondary mounds (Fig 1). No galactorrhea is present. His abdominal examination findings are normal, and he has Tanner V genitalia with normal testes. Based on the history and physical examination findings, blood testing and subsequent imaging are performed and lead to the correct diagnosis. Figure 1. Demonstration of acne and gynecomastia in the 15-year-old boy described in the case. ### Diagnosis The combination of progressive gynecomastia coupled with extensive acne and hypertension in an adolescent male suggested excessive hormone production. This suspicion was confirmed by the finding of elevated serum estradiol, estrone, and dehydroepiandosterone sulfate (DHEA-S) levels ranging from 4 to 30 times the upper limit of normal. In addition, the patient had an elevated 24-hour …

Lessons from extinction can be used in trials designed to pursue a cure for cancer. When cancer cannot be cured, similar strategies may be unwise, and strategies that leverage the adaptations of cancer to therapy should be considered.

OBJECTIVEWith the increasing use of flow diversion as treatment for intracranial aneurysms, there is a concomitant increased vigilance in monitoring complications. The low porosity of flow diverters is concerning when the origins of vessels are covered, whether large circle of Willis branches or critical perforators. In this study, the authors report their experience with flow diverter coverage of the lenticulostriate vessels and evaluate their safety and outcomes.METHODSThe authors retrospectively reviewed 5 institutional databases of all flow diversion cases from August 2012 to June 2018. Information regarding patient presentation, aneurysm location, treatment, and outcomes were recorded. Patients who were treated with flow diverters placed in the proximal middle cerebral artery (MCA), proximal anterior cerebral artery, or distal internal carotid artery leading to coverage of the medial and lateral lenticulostriate vessels were included. Clinical outcomes according to the modified Rankin Scale were reviewed. Univariate and multivariate analyses were performed to establish risk factors for lenticulostriate infarct.RESULTSFifty-two patients were included in the analysis. Postprocedure cross-sectional images were available in 30 patients. Two patients experienced transient occlusion of the MCA during the procedure; one was asymptomatic, and the other had a clinical and radiographic ipsilateral internal capsule stroke. Five patients had transient symptoms without radiographic infarct in the lenticulostriate territory. Two patients experienced in-stent thrombosis, leading to clinical MCA infarcts (one in the ipsilateral caudate) after discontinuing antiplatelet therapy. Discontinuation of dual antiplatelet therapy prior to 6 months was the only variable that was significantly correlated with stroke outcome (p < 0.01, OR 0.3, 95% CI 0–0.43), and this significance persisted when controlled for other risk factors, including age, smoking status, and aneurysm location.CONCLUSIONSThe use and versatility of flow diversion is increasing, and safety data are continuing to accumulate. Here, the authors provide early data on the safety of covering lenticulostriate vessels with flow diverters. The authors concluded that the coverage of these perforators does not routinely lead to clinically significant ischemia when dual antiplatelet therapy is continued for 6 months. Further evaluation is needed in larger cohorts and with imaging follow-up as experience develops in using these devices in more distal circulation.

Objectives A treatment regimen consisting of bendamustine and brentuximab vedotin (BV) has been described as a highly potent salvage therapy and as an effective induction therapy leading to high response rates before autologous stem cell transplantation (ASCT) in patients with classical Hodgkin lymphoma (cHL). In this retrospective analysis, we aimed to assess this therapy's efficacy in unselected patients with cHL and CD30+ peripheral T‐cell lymphoma (PTCL). Patients and methods Data of 28 patients with cHL and five patients with PTCL treated with a combination of bendamustine and BV at three Austrian tertiary cancer centers were analyzed. Results In patients with cHL, the ORR was 100% (78.6% CR, 21.4% PR). After 17 months median follow‐up, median survival times were not reached; 1‐year PFS was 81.9%, and 1‐year OS was 95.7%. Thirteen eligible patients (46.4%) successfully underwent planned ASCT after salvage therapy with bendamustine and BV and subsequent high‐dose chemotherapy. Three of the five PTCL patients achieved CR, while two did not respond and died during or shortly after therapy. Conclusion A combination of bendamustine and BV is an effective salvage and induction therapy before ASCT in patients with relapsed/refractory cHL. Further research is warranted to evaluate the use in patients with PTCL.

Wir berichten uber eine 43-jahrige Frau, die sich mit Kopfschmerzen und Parasthesien nach einem Sturz auf den Kopf beim Skifahren in der Notaufnahme vorstellte. Sie hatte klinische Zeichen eines Volumenmangels und eine schwere Hyponatriamie. Die zerebrale Bildgebung war unauffallig. Es wurde die Diagnose eines zerebralen Salzverlustsyndroms („salt wasting syndrome“ [CSW]) gestellt. Das CSW wird als extrazellularer Volumenmangel aufgrund eines tubularen Defekts im Natriumtransport bei Patienten mit normaler Nebennieren- und Schilddrusenfunktion definiert. Die Erkrankung entsteht meist sekundar zu neurologischen Erkrankungen oder Kopfverletzungen. Der Zustand unserer Patientin verbesserte sich schnell nach Volumengabe und der Therapie mit Mineralokortikoiden. Die Unterscheidung zwischen CSW und dem Syndrom der inadaquaten Sekretion von antidiuretischem Hormon (SIADH) kann eine Herausforderung darstellen, ist aber wichtig, da sich die Behandlung grundlegend unterscheidet.

Introduction Tetanus, diphtheria, and acellular pertussis (Tdap) and influenza vaccines are recommended for pregnant women in each pregnancy, yet uptake is suboptimal. This study tested the efficacy of an online vaccine resource in increasing uptake of Tdap and influenza vaccines among pregnant women. Study design RCT. Setting/participants This study was conducted among women in the third trimester of pregnancy in an integrated healthcare system in Colorado in September 2013–July 2016, with data analysis in 2017–2018. Intervention Women were randomly assigned to 1 of 3 arms: website with vaccine information and interactive social media components, website with vaccine information only, or usual care. Participants in the website with vaccine information and interactive social media components and website with vaccine information only arms had access to the same base vaccine content. The website with vaccine information and interactive social media components also included a blog, discussion forum, and “Ask a Question” portal. Main outcome measures Tdap and influenza vaccination. These outcomes were analyzed separately. Results For influenza (n=289), women in both the website with vaccine information and interactive social media components (OR=2.19, 95% CI=1.06, 4.53) and website with vaccine information only (OR=2.20, 95% CI=1.03, 4.69) arms had higher vaccine uptake than the usual care arm. The proportions of women receiving the influenza vaccine were 57%, 55%, and 36% in the website with vaccine information and interactive social media components, website with vaccine information only, and usual care arms, respectively. For Tdap (n=173), there were no significant differences in vaccine uptake between study arms. The proportions of women receiving Tdap were 71%, 69%, and 68% in the website with vaccine information and interactive social media components, website with vaccine information only, and usual care arms, respectively. Conclusions Web-based vaccination information sent to pregnant women can positively influence maternal influenza vaccine uptake. Because of potential scalability, the impact of robust vaccination information websites should be studied in other settings. Trial registration This study is registered at www.clinicaltrials.gov NCT01873040.

Atrial natriuretic peptide (NP) and BNP increase cGMP, which reduces blood pressure and cardiac hypertrophy by activating guanylyl cyclase (GC)-A, also known as NPR-A or Npr1. Although GC-A is highly phosphorylated, and dephosphorylation inactivates the enzyme, the significance of GC-A phosphorylation to heart structure and function is unknown. To identify in vivo processes that are regulated by GC-A phosphorylation, we substituted glutamates for known phosphorylation sites to make GC-A(8E/8E) mice that express an enzyme that cannot be inactivated by dephosphorylation. GC-A activity, but not protein, was increased in heart and kidney membranes from GC-A(8E/8E) mice. Activities were 3-fold higher in female compared to male cardiac ventricles. Plasma cGMP and testosterone were elevated in male and female GC-A(8E/8E) mice, but aldosterone was only increased in mutant male mice. Plasma and urinary creatinine concentrations were decreased and increased, respectively, but blood pressure and heart rate were unchanged in male GC-A(8E/8E) mice. Heart weight to body weight ratios for GC-A(8E/8E) male, but not female, mice were 12% lower with a 14% reduction in cardiomyocyte cross sectional area. Subcutaneous injection of fsANP, a long-lived ANP analog, increased plasma cGMP and decreased aldosterone in male GC-A(WT/WT) and GC-A(8E/8E) mice at 15 minutes, but only GC-A(8E/8E) mice had elevated levels of plasma cGMP and aldosterone at 60 minutes. fsANP reduced ventricular ERK1/2 phosphorylation to a greater extent and for a longer time in the male mutant compared to WT mice. Finally, ejection fractions were increased in male but not female hearts from GC-A(8E/8E) mice. We conclude that increased phosphorylation-dependent GC-A activity decreases cardiac ERK activity, which results in smaller male hearts with improved systolic function.

Objectives To evaluate pathologic findings and access risk factors in premenopausal patients with hormone receptor-positive metastatic breast cancer undergoing bilateral salpingo-oophorectomy (BSO) for hormone supression. Methods We retrospectively analyzed data of 170 premenopausal patients with hormone receptor-positive metastatic breast cancer who had been submitted to BSO for ovarian supression between 2009 and 2021 at a terciary hospital in Sao Paulo, Brazil. All patients were metastatic at the time of surgery, but none had known ovarian metastasis. Patients with preoperative suspicion for malignancy in ovaries were not included. The following characteristics were analyzed: age, BMI, histological type, molecular subtype, HER2 status, initial TNM staging, sites of distant metastases at surgery, number of sites of distant metastases at surgery and the family history of cancer. Results A total of 170 patients were included. The characteristics of the studied patients are described in table 1. Unknown ovarian metastases of breast cancer were found in 40 patients (23,5%). Multivariate analyses revealed that younger ages (OR, 0.94; 95% CI, 0.88 to 0.99; p=0.04) and the number of sites of metastasis at surgery (≥ 3 sites; OR, 3.99; 95% CI, 1.37 to 11.59; p=0.01) were significantly related with breast cancer ovarian metastases. The remaining studied characteristics were not statistically significant. Conclusions Younger ages and having 3 or more sites of metastases at surgery appears to be risk factors for ovarian implants in previously metastatic breast cancer patients.

Objectives Evaluation of ovarian cysts (OCy) are specially challenging in patients with a history of breast cancer (BC). We aimed to characterize a population of BC patients submitted to oophorectomy for OCy and establish risk factors for malignant findings on surgical specimen. Methods All BC patients treated with oophorectomy for OCy between 2008–2021 at a tertiary hospital,were retrospectively reviewed. Results 66 patients were eligible.Characteristics are described in table 1. Most (71.2%) had no cancer/benign lesions in the surgical specimens of the ovaries,10.6% had ovarian cancer,15.2% had BC metastasis and 3% had borderline lesions. Between the no cancer/benign/borderline the median IOTA-ADNEX/benign was 92.5%(IQR 62.6–96.6). Between the ovarian cancer the median IOTA-ADNEX/primary-malign was 83.7%(IQR 41–89.1). In the metastatic lesions the median IOTA-ADNEX/secondary-malign was 1.5%(IQR 0.3–12). The following variables were associated with a greater risk of malign ovarian histology: metastatic BC at diagnosis(p=0.01),ascites(p=0.004), elevated CA125(p=0.01), elevated CA15.3(p=0.002). Table 1. Conclusions CA125/CA15.3 are good pre-operative markers,IOTA-ADNEX is a good tool to distinguish bening cysts and OC.

Purpose To assess surgical success and the post-operative development of intraocular pressure between XEN45® gelstent, Preserflo® MicroShunt and trabeculectomy with mitomycin C. Methods Data from 105 eyes from 105 patients of matched cases with refractory open-angle glaucoma, who underwent surgery between January 2019, and August 2020, were evaluated. Patients underwent either stand-alone XEN gelstent insertion with Mitomycin C, stand-alone Preserflo with Mitomycin C or trabeculectomy with Mitomycin C. The primary outcome was the proportion of complete surgical success at 6 months post-operatively (i.e. intraocular pressure between 5mmHg and 18mmHg, no revision surgery, no loss of light perception and no post-operative pharmaceutical antiglaucomatous treatment). The reduction of intraocular pressure after 6 months, the classes of antiglaucomatous medication used post-operatively, best-corrected visual acuity, spherical refractive errors and astigmatism were assessed as secondary outcomes. Results We included 35 eyes in each group. After 6-month follow-up, complete success was 73.5% [95%-CI: 57.9%-89.2%] in the trabeculectomy group, 51.4% [95%-CI: 34.0%-68.8%] in the XEN group and 74.2% [95%-CI: 57.9%-90.5%] in the Preserflo group (p = 0.08). Regarding secondary outcomes, the reduction of intraocular pressure was 12.1 ± 7.9 mmHg in the trabeculectomy group and was thereby 5.8 [95%-CI: 2.2-9.6] mmHg greater compared with the XEN group (p Conclusions No statistically significant differences were found between trabeculectomy, XEN45® gelstent implantation and Preserflo® MicroShunt implantation regarding surgical success after 6 months. Yet reduction in intraocular pressure was significantly higher in the trabeculectomy group. However, all three interventions resulted in sufficiently low post-operative intraocular pressure and may therefore be considered individually for glaucoma treatment.

A potential manner to lower the morbidity with the hypertensive disoreders of pregancy is to explore the time of day of delivery.To compare composite neonatal adverse outcomes among term women with hypertensive disorders.This population-based cohort study used the U.S. vital statistics dataset from 2013 to 2017. Time of delivery was categorized into three shifts. The primary outcome was composite neonatal adverse outcome..Compared to neonates delivered at the first shift, the risk of composite neonatal adverse outcome was higher at the third shift (aRR = 1.19, 95% CI = 1.13-1.25).the risk of composite neonatal adverse outcome is higher if the delivery occurs at the third (23:00-7:00) shift.

Objective To compare the maternal and neonatal adverse outcomes among individuals with one or two prior cesarean deliveries who are induced at 39 weeks gestational age versus those that are expectantly managed. Methods This was a population-based cross-sectional study using U.S. National Vital Statistics 2014-2018 period linked birth and infant death data. Cohorts were individuals with one or two prior cesarean deliveries who were induced at 39.0 to 39.6 weeks gestation or underwent delivery from 40.0 to 41.6 weeks gestational age from either spontaneous labor or induction. The primary outcome was a composite of maternal adverse outcomes: admission to the intensive care unit, transfusion, uterine rupture, or unplanned hysterectomy. The secondary outcome was a composite of neonatal adverse outcomes, including: 5-minute Apgar score 6 h, neonatal seizures, or neonatal mortality (death within 27 days of birth). Results Of 263,489 women who met the inclusion criteria 21,951 (8.3%) underwent induction at 39 weeks. The composite maternal adverse outcome was significantly higher in women who delivered at 40-41 weeks gestation when compared to the 39 week gestation induction of labor cohort (8.1 versus 9.4 per 1,000 births; aRR 1.18; 95% CI 1.01-1.39). The overall rate of composite neonatal adverse outcome was 10.4 per 1,000 live births. The composite neonatal adverse outcome was also significantly elevated among deliveries at 40-41 weeks gestation as well (8.6 vs. 10.8 per 1,000 live births; aRR 1.31; 95%CI 1.12-1.53). Conclusion In women undergoing trial of labor after cesarean, induction of labor at 39 weeks gestation was associated with fewer maternal and neonatal adverse outcomes when compared to delivery at 40-41 weeks gestation.

BACKGROUND: Youth are vulnerable to opioid use initiation and its complications. With growing rates of opioid overdose, strategies to identify youth at risk of opioid use disorder (OUD) to efficiently focus prevention interventions are needed. This study developed and validated a prediction model of OUD in youth aged 14–18 years. METHODS: The model was developed in a Colorado healthcare system (derivation site) using Cox proportional hazards regression analysis. Model predictors and outcomes were identified using electronic health record data. The model was externally validated in a separate Denver safety net health system (validation site). Youth were followed for up to 3.5 years. We evaluated internal and external validity using discrimination and calibration. RESULTS: The derivation cohort included 76,603 youth, of whom 108 developed an OUD diagnosis. The model contained 3 predictors (smoking status, mental health diagnosis, and non-opioid substance use or disorder) and demonstrated good calibration (p=0.90) and discrimination (bootstrap-corrected C-statistic = 0.76: 95% CI = 0.70, 0.82). Sensitivity and specificity were 57% and 84% respectively with a positive predictive value (PPV) of 0.49%. The validation cohort included 45,790 youth of whom, 74 developed an OUD diagnoses. The model demonstrated poorer calibration (p

BACKGROUND: A recent childhood vaccine promotion intervention trial showed no effects on vaccination outcomes relative to usual care. The purpose of this paper was to test assumptions and theory-based relationships underlying hypothesized mechanisms for two vaccine promotion educational websites (one tailored to parental values, beliefs, and intentions; one untailored) compared to usual care. METHOD: This is a secondary analysis of a three-arm randomized controlled trial. Parental vaccine values, hesitancy, attitudes, and intention to vaccinate surveys were administered at baseline (≤ 2 mos) and at 4–6 and 10–12 months of age. Vaccination was assessed using electronic health records. Analyses included random coefficient models and risk differences with exact confidence limits. RESULTS: Parental vaccine values were mostly stable over time. Vaccine attitudes were generally positive, with no differences among study arms. Both tailored and untailored website arms showed similar increases in intention to vaccinate more than usual care. Positive changes in intentions were associated with lower rates of late vaccination. CONCLUSIONS: While attitudes and intentions predicted vaccination behavior and the intervention increased intention to vaccinate all on time, the web-based education and values-tailored messaging approaches were not effective at increasing vaccination rates. Intentions are necessary but insufficient targets for vaccine promotion interventions.

Purpose To evaluate long-term results of glaucoma surgery in newborn and infants with glaucoma. Methods Seventy-nine eyes of 52 children (age: 3 weeks-15.3 years) with primary congenital or secondary glaucoma treated between 2015 and 2017 were included. The median follow-up time was 3.9 years. Conventional probe trabeculotomy, 360° catheter-assisted trabeculotomy, filtering and cyclodestructive surgery were compared. Strict criteria for surgical success were applied: Complete surgical success (IOP below target IOP, no further surgery) and incomplete surgical success (additional surgery allowed) were analyzed, and IOP at baseline and last follow-up was compared. Results Intraocular pressure (IOP) was significantly reduced in primary congenital (preoperative IOP: 27.8 ± 7.5 mmHg vs. postoperative IOP: 14.2 ± 4.5 mmHg) and secondary glaucoma (preoperative IOP: 29.2 ± 9.1 mmHg vs. postoperative IOP: 16.6 ± 4.7 mmHg). 90% of all eyes reached target IOP with or without medication allowing for additional surgeries. As first surgery, 360° catheter-assisted trabeculotomy had a tendency to higher surgical success than other surgical approaches, while cyclodestructive procedures had lowest. Conclusions We found very promising surgical results in our childhood glaucoma patient group. Surgical success in both congenital and secondary glaucoma was high.

Activating mutations in the fibroblast growth factor receptor 3 (FGFR3) or inactivating mutations in guanylyl cyclase B (GC-B), also known as NPR-B or Npr2, cause short-limbed dwarfism. FGFR3 activation causes dephosphorylation and inactivation of GC-B, but the contribution of GC-B dephosphorylation to achondroplasia (ACH) is unknown. GC-B7E/7E mice that express a glutamate-substituted version of GC-B that cannot be inactivated by dephosphorylation were bred with mice expressing FGFR3-G380R, the most common human ACH mutation, to determine if GC-B dephosphorylation is required for ACH. Crossing GC-B7E/7E mice with FGFR3G380R/G380R mice increased naso-anal and long (tibia and femur), but not cranial, bone length twice as much as crossing GC-B7E/7E mice with FGFR3WT/WT mice from 4 to 16 weeks of age. Consistent with increased GC-B activity rescuing ACH, long bones from the GC-B7E/7E/FGFR3G380R/G380R mice were not shorter than those from GC-BWT/WT/FGFR3WT/WT mice. At two weeks of age, male but not female FGFR3G380R/G380R mice had shorter long bones and smaller growth plate hypertrophic zones, whereas female but not male GC-B7E/7E mice had longer bones and larger hypertrophic zones. In two-week old males, crossing FGFR3G380R/G380R mice with GC-B7E/7E mice increased long bone length and hypertrophic zone area to levels observed in mice expressing wild type versions of both receptors. We conclude that preventing GC-B dephosphorylation rescues reduced axial and appendicular skeleton growth in a mouse model of achondroplasia.

PURPOSE Oral anticancer drugs (eg, kinase inhibitors) play an important role in cancer therapy. However, considerable challenges regarding medication safety of oral anticancer drugs have been reported. Randomized, controlled, multicenter studies on the impact of intensified clinical pharmacological/pharmaceutical care on patient safety and patient treatment perception are lacking. METHODS Patients were eligible for the randomized, multicenter AMBORA study, if they were newly started on any of the oral anticancer drugs approved in 2001 or later without restriction to certain tumor entities. Patients were randomly assigned to receive either standard of care (control group) or an additional, intensified clinical pharmacological/pharmaceutical care, which included medication management and structured patient counseling, over a period of 12 weeks (intervention group). Primary end points were the number of antitumor drug–related problems (ie, side effects and unresolved medication errors) and patient treatment satisfaction with the oral anticancer therapy after 12 weeks measured with the Treatment Satisfaction Questionnaire for Medication, category convenience. RESULTS Two hundred two patients were included. Antitumor drug–related problems were significantly lower in the intervention compared with the control group (3.85 v 5.81 [mean], P < .001). Patient treatment satisfaction was higher in the intervention group (Treatment Satisfaction Questionnaire for Medication, convenience; 91.6 v 74.4 [mean], P < .001). The hazard ratio for the combined end point of severe side effects (Common Terminology Criteria for Adverse Events ≥ 3), treatment discontinuation, unscheduled hospital admission, and death was 0.48 (95% CI, 0.32 to 0.71, P < .001) in favor of the intervention group. CONCLUSION Treatment with oral anticancer drugs is associated with a broad range of medication errors and side effects. An intensified clinical pharmacological/pharmaceutical care has considerable, positive effects on the number of medication errors, patient treatment perception, and severe side effects.

Background and Purpose— Stroke etiology drives thrombus composition. We thus hypothesized that endovascular treatment shows different efficacy in cardioembolic versus noncardioembolic large-vessel occlusions (LVOs). Methods— Procedural characteristics, grade of reperfusion, and functional outcome at discharge and 90 days were compared between patients with cardioembolic versus noncardioembolic LVO from the GSR-ET (German Stroke Registry–Endovascular Treatment; n=2589). To determine associations with functional outcome, adjusted odds ratios and 95% CIs were calculated using ordinal multivariable logistic regression models adjusting for potential baseline confounder variables. Results— Endovascular treatment of cardioembolic LVO had a higher rate of successful reperfusion (85.6% versus 81.0%; P =0.002) and a higher rate of complete reperfusion after a single thrombectomy pass (45.7% versus 38.1%; P Conclusions— These results provide evidence for higher efficacy of endovascular treatment in cardioembolic LVO compared with noncardioembolic LVO.

Background Hypothalamic hamartomas (HH) are a challenging pathology that cause gelastic seizures. Magnetic Resonance Imaging-guided Laser Interstitial Thermal Therapy (MRgLITT) offers a safe and effective treatment for HHs via a minimally invasive technique. Objective To determine how clinical outcome correlates to residual tumor volume and surgical strategy by analyzing radiographic data and reconstructing volumetric imaging. Methods Clinical and radiographic information of 58 pediatric patients who underwent MRgLITT for HH with at least 6 mo of follow-up were retrospectively reviewed. MR imaging was volumetrically reconstructed to analyze the impact of hamartoma and ablation volumes on outcome. Primary outcome measure was freedom from gelastic seizures. Results Eighty-one percent of patients were completely free of gelastic seizures at last follow-up; of 22 patients with secondary nongelastic epilepsy, 15 were free of additional seizures. Postoperative complication rate was low. There was no significant difference in gelastic seizure outcome related to pre- or postoperative hamartoma size. Residual hamartoma percentage in those free of gelastic seizures was 43% compared to 71% in those with continued seizures (P = .021). Larger hamartomas required multiple ablations to achieve seizure freedom. Conclusion This large series of patients confirms the safety and efficacy of MRgLITT for pediatric HH and describes morphological considerations that predict success. Our data suggest that complete ablation of the lesion is not necessary, and that the focus should be on appropriate disconnection of the epileptogenic network. We have found that a staged approach to hamartoma ablation allows adequate disconnection of the hamartoma while mitigating risk to surrounding structures.

Purpose: BN-CV301 is a poxviral-based vaccine comprised of recombinant (rec.) modified vaccinia Ankara (MVA-BN-CV301; prime) and rec. fowlpox (FPV-CV301; boost). Like its predecessor PANVAC, BN-CV301 contains transgenes encoding tumor-associated antigens MUC1 and CEA as well as costimulatory molecules (B7.1, ICAM-1, and LFA-3). PANVAC was reengineered to make it safer and more antigenic. Patients and Methods: This open-label, 3+3 design, dose-escalation trial evaluated three dose levels (DL) of MVA-BN-CV301: one, two, or four subcutaneous injections of 4 × 108 infectious units (Inf.U)/0.5 mL on weeks 0 and 4. All patients received FPV-CV301 subcutaneously at 1 × 109 Inf.U/0.5 mL every 2 weeks for 4 doses, then every 4 weeks. Clinical and immune responses were evaluated. Results: There were no dose-limiting toxicities. Twelve patients enrolled on trial [dose level (DL) 1 = 3, DL2 = 3, DL3 = 6). Most side effects were seen with the prime doses and lessened with subsequent boosters. All treatment-related adverse events were temporary, self-limiting, grade 1/2, and included injection-site reactions and flu-like symptoms. Antigen-specific T cells to MUC1 and CEA, as well as to a cascade antigen, brachyury, were generated in most patients. Single-agent BN-CV301 produced a confirmed partial response (PR) in 1 patient and prolonged stable disease (SD) in multiple patients, most notably in KRAS-mutant gastrointestinal tumors. Furthermore, 2 patients with KRAS-mutant colorectal cancer had prolonged SD when treated with an anti-PD-L1 antibody following BN-CV301. Conclusions: The BN-CV301 vaccine can be safely administered to patients with advanced cancer. Further studies of the vaccine in combination with other agents are planned. See related commentary by Repáraz et al., p. 4871

The North Carolina Area Health Education Center (NC AHEC) Registered Nurse (RN) Refresher Program maintains compliance with the North Carolina Board of Nursing regulations to ensure the safety of the public. The program is for nurses who have inactive or expired RN licenses or who wish to update their nursing skills. To modernize the program, faculty and staff from the University of North Carolina at Chapel Hill William and Ida Friday Center for Continuing Education, the University of North Carolina School of Nursing, and the NC AHEC Program Offices conducted an extensive program evaluation from 2014 through 2015 using the Centers for Disease Control and Prevention Framework for Program Evaluation in Public Health. A collaborative statewide team of experts subsequently developed a plan for a comprehensive program revision. The revision incorporated contemporary practice using evidence-based research, technology, quality and safety, and healthcare legislation as themes. In addition, the theory portion of the NC AHEC RN Refresher Program was redesigned and is now offered only online to better serve RNs in North Carolina, the United States, and English speakers across the world.

Abstract. Background: An important consideration when conducting randomized controlled trials is treatment differentiation. Direct observation helps ensure that providers in different treatment groups are delivering distinct interventions. One direct observation method is the use of a measure to rate clinician performance when delivering an intervention. Aims: This generalizability study evaluated the reliability of the CAMS Rating Scale (CRS), a measure used to assess delivery of the Collaborative Assessment and Management of Suicidality (CAMS). Method: Digitally recorded tapes of clinicians delivering either CAMS or Enhanced Care-As-Usual (E-CAU) were coded using the CRS. Sessions ( N = 36) were each coded by two raters, and encompassed four clinicians, four time points, and 34 unique patients across two treatment groups. A reliability coefficient (i.e., G coefficient) and the percentages of variance contributed by each component of the measurement model were obtained. Results: The CRS reliably differentiates CAMS from E-CAU, minimizes measurement error relative to expected variance sources, and continues to demonstrate high inter-rater reliability. Limitations: The absence of blind raters, a formal training protocol for the rating team, and ratings from all clinician–patient dyads at all time points was a limitation. Conclusion: The CRS is a reliable treatment differentiation measure that can play an integral role in studies evaluating CAMS.

Patients with complex, multisutural, and syndromic craniosynostosis (CSO) frequently exhibit intracranial hypertension. The intracranial hypertension cannot be entirely attributed to the craniocephalic disproportion with calvarial restriction because cranial vault expansion has not consistently alleviated elevated intracranial pressure. Evidence has most strongly supported a multifactorial interaction, including venous hypertension along with other pathogenic processes. Patients with CSO exhibit marked venous anomalies, including stenosis of the jugular-sigmoid complex, transverse sinuses, and extensive transosseous venous collaterals. These abnormal intracranial-extracranial occipital venous collaterals might represent anomalous development, with persistence and subsequent enlargement of channels normally present in the fetus, either as a primary defect or as nonregression in response to failure of the development of the jugular-sigmoid complexes. It has been suggested by some investigators that venous hypertension in patients with CSO could be treated directly via jugular foraminoplasty, venous stenting, or jugular venous bypass, although these options are not in common clinical practice. Obstructive sleep apnea, occurring as a consequence of midface hypoplasia, can also contribute to intracranial hypertension in patients with syndromic CSO. Thus, correction of facial deformities, as well as posterior fossa decompression, could also play important roles in the treatment of intracranial hypertension. Determining the precise mechanistic underpinnings underlying intracranial hypertension in any given patient with CSO requires individualized evaluation and management.

Die Diagnosestellung zeitkritischer Patienten ist in einer Notaufnahme von zentraler Bedeutung. Qualitatsindikatoren, zur Diagnosequalitat von Zentralen Notaufnahmen (ZNA) sind kaum verfugbar. Auf der Basis der diagnostischen Ubereinstimmung (dU) von Aufnahme- und Krankenhausentlassdiagnose wurden die diagnostische Sensitivitat (dSe), die diagnostische Spezifitat (dSp) und die diagnostische Effizienz (dEff) fur 28 zeitkritische Indikatordiagnosen aller stationaren ZNA Patienten eines Jahres berechnet. In die Studie wurden 21.512 stationare Patienten (im Mittel 63 Jahre; min. 0, max. 104, SD ± 21,4) mit 599 unterschiedlichen Hauptaufnahmediagnosen eingeschlossen. Bei 21,1 % der Patienten wurde eine Indikatordiagnose gestellt. Die dU und dSe uber alle Indikatordiagnosen betragt 66,5 % bzw. 70,0 % und die dSp 58,8 %. Fur Patienten mit Aortenaneurysma/-dissektion wurde mit 100 % die hochste dSe (dSp 72 %) und fur die intrakraniellen Verletzungen mit 94 % die hochste dSp (dSe 92 %) erzielt. Bei der Meningitis war die dSe mit 22 % am niedrigsten. Diagnosen mit groser Differenz zwischen dSe und dSp waren z. B. die Gefaskrankheiten des Darms (K55) mit 82 % dSe und 13 % dSp. Die dEff aller Indikatordiagnosen liegt bei 0,37/minute (min. 0,03, max. 92, SD ± 1,22). Der Herzstillstand (I46) erreicht mit 1,04/minute (min. 0,42, max. 9,17, SD ± 1,41) die hochste mittlere dEff (dSe 55 %; mittlere Verweildauer 53 min). Qualitatsindikatoren fur zeitkritische Indikatordiagnosen konnen aus Routinedaten erhoben werden. Durch die Verknupfung von Kennzahlen der Prozess- und Ergebnisqualitat kann die Diagnosequalitat einer ZNA objektiv dargestellt werden.

Background Vein of Galen malformations (VOGM) comprise nearly a third of pediatric cerebrovascular anomalies, with potentially devastating neurological and systemic complications. Advances in endovascular therapies have dramatically improved outcomes compared to historical surgical treatments, and neurosurgeons are an essential component of the multidisciplinary critical care team. Objective To retrospectively review pediatric patients with VOGM treated at Texas Children's Hospital (TCH), a quaternary referral center, over 15 yr, and present lessons learned in treating children with modern endovascular techniques. Methods Charts from TCH were retrospectively reviewed for the past 15 yr. Patients with diagnosis including "Vein of Galen," "Vein of Galen malformation," "Vein of Galen aneurysmal malformation," or any abbreviations (ie, VOG, VOGM, VOGAM) were reviewed. Presentation, imaging, treatment specifics, and clinical outcomes were reported. Results There were 18 patients with VOGM managed at TCH from 2002 to 2018 with a total of 29 embolizations. Seventeen were performed with a single embolisate (NBCA or Onyx), and 12 with a combination. A dual lumen balloon catheter was used as an adjunct in 3 embolizations. Complications occurred in 5 embolizations (24%), including hemorrhage, embolisate migration, and femoral vessel occlusion. Surviving patients were followed for a mean of 38 mo, with 12 having normal or near-normal neurological development. Conclusion VOGM can present with a myriad of neurological and systemic symptoms, potentially in extremis. Neurosurgical involvement in these cases is critical, as urgent treatment can be lifesaving. Patients may require multiple treatment sessions using a variety of endovascular tools and techniques.

Although many patients with newly diagnosed Ewing sarcoma can become long-term survivors, relapse remains an important clinical problem for which there is no standard approach. Several prognostic factors have been identified, and these may help guide patient counseling and therapy decisions. A variety of chemotherapy regimens have produced responses in patients with recurrent Ewing sarcoma, but no comparative studies have been completed to show superiority of any one particular approach. In addition, the optimum length of therapy for salvage regimens and use of local control measures remains unknown. The likelihood of cure remains low and the gaps in our knowledge are great, and so enrollment on clinical trials should be strongly encouraged for these patients when feasible. Because Ewing sarcoma is relatively rare, some pediatric and adult oncologists may be less familiar with the management of relapsed patients. In this review, we address common questions facing the clinician and patient, and provide an update on new strategies for therapy.

Introduction Breast cancer diagnosed in young women who are 40 years (yrs) or younger is a relatively rare disease. However, it represents the most common cause of cancer-related deaths in this age-group. Furthermore, young age at diagnosis is associated with an increased risk of recurrence and worse survival. To date, general concepts concerning oncological cancer management should be driven by clinicopathological tumor characteristics and should adhere to standardized protocols for patients in general, but little is known about the oncological cancer treatment and outcome of this very young women in today's clinical practice. Patients and Methods The breast cancer in pregnancy registry study (BCP/GBG29/BIG 03-02) is a multicenter, international, observational study. BCP was established to investigate the oncological management and outcome of breast cancer in pregnancy. Since 2014 non-pregnant patients who are 40 yrs or younger are eligible if diagnosed with histological confirmed invasive breast cancer, independent of the type of treatment as control cohort. All patients received oncological treatment according to local standards. In this study the following endpoints will be analyzed descriptively for the young non-pregnant women cohort: breast cancer staging at diagnosis, biological characteristics of breast cancer at diagnosis, diagnostic procedures, treatment modalities, toxicity, pathological complete response after neoadjuvant chemotherapy, disease-free survival and overall survival. Results From February 2014 until June 2018, 969 non-pregnant patients ≤40 yrs have been registered. The median age at diagnosis was 35 yrs (range 19-40). Overall, 90.1% of patients had a stage T1-2 at diagnosis and 67.1% of patients had negative lymph nodes. 86.7% of tumors were invasive ductal carcinomas and 4.1% lobular carcinomas. Grading (G) 3 was reported in 55.5%. 26.6% of tumors were luminal A-like (ER- and/or PgR-positive, HER2-negative, G1-2), 40.0% luminal B-like (ER- and/or PgR-positive, HER2-negative, G3 or ER- and/or PgR-positive, HER2-positive, any G), 7.7% HER2 positive non-luminal-like, and 25.7% triple negative breast cancers. 3.8% of young non-pregnant patients had metastatic disease at primary diagnosis. Conclusion This registry comprises a large cohort of young non-pregnant patients with breast cancer diagnosed at the age of 40 yrs or younger and provides important data about a modern breast cancer treatment as well as oncological outcome in this setting of young women. Further results including oncological management, toxicity, and survival will be presented at the meeting. Citation Format: Seiler S, Schmatloch S, Reinisch M, Neunhöffer T, Schmidt M, Bechtner C, Marmé F, Wagner M, Möbus V, Reimer T, Kleine-Tebbe A, Sinn B, Stickeler E, Untch M, Janni W, Seither F, Loibl S. Cancer management and outcome of very young non-pregnant patients with breast cancer diagnosed at 40 years or younger– GBG 29 [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P1-17-07.

OBJECTIVEAppropriately chosen candidates with medically refractory epilepsy may benefit from hemispheric disconnection. Traditionally, this involves a large surgical exposure with significant associated morbidity. Minimally invasive approaches using endoscopic assistance have been described by only a few centers. Here, the authors report on the feasibility of endoscope-assisted functional hemispherotomy in a cadaver model and its first translation into clinical practice in appropriately selected patients.METHODSThree silicone-injected, formalin-fixed cadaver heads were used to establish the steps of the procedure in the laboratory. The steps of disconnection were performed using standard surgical instruments and a straight endoscope. The technique was then applied in two patients who had been referred for hemispherectomy and had favorable anatomy for an endoscope-assisted approach.RESULTSAll disconnections were performed in the cadaver model via a 4 × 2–cm paramedian keyhole craniotomy using endoscopic assistance. An additional temporal burr hole approach was marked in case the authors were unable to completely visualize the frontobasal and insular cuts from the paramedian vertical view. Their protocol was subsequently used successfully in two pediatric patients. Full disconnection was verified with postoperative tractography.CONCLUSIONSFull hemispheric disconnection can be accomplished with minimally invasive endoscope-assisted functional hemispherotomy. The procedure is technically feasible and can be safely applied in patients with favorable anatomy and pathology; it may lead to less surgical morbidity and faster recovery.

Madagascar is more seriously affected by plague, a zoonosis caused by Yersinia pestis, than any other country. The Plague National Control Program was established in 1993 and includes human surveillance. During 1998-2016, a total of 13,234 suspected cases were recorded, mainly from the central highlands; 27% were confirmed cases, and 17% were presumptive cases. Patients with bubonic plague (median age 13 years) represented 93% of confirmed and presumptive cases, and patients with pneumonic plague (median age 29 years) represented 7%. Deaths were associated with delay of consultation, pneumonic form, contact with other cases, occurrence after 2009, and not reporting dead rats. A seasonal pattern was observed with recrudescence during September-March. Annual cases peaked in 2004 and decreased to the lowest incidence in 2016. This overall reduction occurred primarily for suspected cases and might be caused by improved adherence to case criteria during widespread implementation of the F1 rapid diagnostic test in 2002.

Exposures to endocrine-disrupting chemicals (EDCs) affect the development of hormone-sensitive neural circuits, the proper organization of which are necessary for the manifestation of appropriate adult social and sexual behaviors. We examined whether prenatal exposure to polychlorinated biphenyls (PCBs), a family of ubiquitous industrial contaminants detectable in virtually all humans and wildlife, caused changes in sexually-dimorphic social interactions and communications, and profiled the underlying neuromolecular phenotype. Rats were treated with a PCB commercial mixture, Aroclor 1221 (A1221), estradiol benzoate (EB) as a positive control for estrogenic effects of A1221, or the vehicle (4% DMSO), on embryonic day (E) 16 and 18. In adult F1 offspring, we first conducted tests of ultrasonic vocalization (USV) calls in a sociosexual context as a measure of motivated communications. Numbers of certain USV call types were significantly increased by prenatal treatment with A1221 in males, and decreased by EB in females. In a test of sociosexual preference for a hormone-vs. a non-hormone-primed opposite sex conspecific, male (but not female) nose-touching with opposite-sex rats was significantly diminished by EDCs. Gene expression profiling was conducted in two brain regions that are part of the social decision-making network in the brain: the medial preoptic nucleus (MPN) and the ventromedial nucleus (VMN). In both regions, many more genes were affected by A1221 or EB in females than males. In female MPN, A1221 changed expression of steroid hormone receptor and neuropeptide genes (e.g., Ar, Esr1, Esr2, and Kiss1). In male MPN, only Per2 was affected by A1221. The VMN had a number of genes affected by EB compared to vehicle (females: Kiss1, Kiss1r, Pgr; males: Crh) but not A1221. These differences between EB and A1221 indicate that the mechanism of action of A1221 goes beyond estrogenic pathways. These data show sex-specific effects of prenatal PCBs on adult behaviors and the neuromolecular phenotype.

Research Objectives To evaluate the prevalence of cannabis use for MS symptom management and factors associated with its use among current users in the North American Research Committee on Multiple Sclerosis (NARCOMS) registry. Design An online, supplemental survey regarding use of tetrahydrocannabinol (THC)-containing cannabis for MS symptoms. Setting A voluntary, self-report registry for PwMS. Participants Active, US NARCOMS participants (N=6934), of whom 3249 (47%;) responded to the survey. Interventions Not applicable. Main Outcome Measures The prevalence of, and reasons for, using or not using cannabis, as well as behaviors and attitudes of current users. Findings were summarized using descriptive statistics. Results The proportion of respondents who reported using cannabis for MS symptoms was 31%. Among the 69% of respondents who did not use cannabis for MS symptoms, the most common reasons were insufficient efficacy (40%) or safety (27%) data. Overall, 636 respondents (20%) reported current use (within last 30 days). Smoking (33%) and eating (20%) were the two most common primary modes of administration. A portion of current users started cannabis before using a prescribed MS symptom management drug (23%) or rehabilitation therapy (45%). The most common target symptoms were spasticity (80%), pain (69%), and sleep problems (61%). Of the 511 current users treating spasticity, 321 (63%) were using additional symptom management therapies (59% using drugs; 11% using physical/occupational therapy) and 190 (37%) were using only cannabis. Conclusions Although concerns about efficacy, safety, and other factors prevent some PwMS from trying cannabis, 31% have tried and 20% are currently using non-FDA-approved cannabis products for MS symptom relief. Of those currently using cannabis to treat spasticity, over a third were using only cannabis. Funding: Greenwich Biosciences, Inc. Author(s) Disclosures Joanne Wagner, Kathryn Nichol, and Joshua Steinerman have a financial relationship with Greenwich Biosciences. Amber Salter has nothing to disclose. Robert Fox has a financial relationship with AB Science, Actelion, Biogen, Celgene, EMD Serono, Genentech, Immunic, Novartis, Sanofi, and TG Therapeutics. Gary Cutter has a financial relationship with Antisense Therapeutics, Astra-Zeneca, Avexis Pharmaceuticals, Biodelivery Sciences International, Biogen, Biolinerx, Brainstorm Cell Therapeutics, Bristol Meyers Squibb/Celgene, Click Therapeutics, CSL Behring, Galmed Pharmaceuticals, Genentech, Genzyme, GreenValley Pharma Ltd, GW Pharmaceuticals, Klein-Buendel Incorporated, Mapi Pharmaceuticals LTD, Medday, Medimmune/Viela Bio, Merck, Merck/Pfizer, Merck/Serono, Immunic, Neurim, Neurogenesis LTD, Novartis, Novartis, OncoImmune, Ophazyme, Opko Biologics, Osmotica Pharmaceuticals, Perception Neurosciences, Reata Pharmaceuticals, Reckover Pharmaceuticals, Recursion/Cerexis Pharmaceuticals, Regeneron, Roche, SAB BIotherapeutics, Sanofi-Aventis, Teva pharmaceuticals, TG Therapeutics, VielaBio Inc, and Vivus. Karry Smith has a financial relationship with Abbott/St Jude, Boston Scientific, Greenwich Biosciences, and Medtronic.