Citations

Objective: Takotsubo syndrome (TTS) is characterized by acute left ventricular dysfunction, which can contribute to intraventricular thrombus and embolism. Still, prevalence and clinical impact of thrombus formation and embolic events on outcome of TTS patients remain unclear. This study aimed to investigate clinical features and outcomes of patients with and without intraventricular thrombus or embolism. Additionally, factors associated with thrombus formation or embolism, as well as predictors for mortality, were identified. Approach and Results: TTS patients enrolled in the International Takotsubo Registry at 28 centers in Australia, Europe, and the United States were dichotomized according to the occurrence/absence of intraventricular thrombus or embolism. Patients with intraventricular thrombus or embolism were defined as the ThrombEmb group. Of 1676 TTS patients, 56 (3.3%) patients developed intraventricular thrombus and/or embolism following TTS diagnosis (median time interval, 2.0 days [range, 0–38 days]). Patients in the ThrombEmb group had a different clinical profile including lower left ventricular ejection fraction, higher prevalence of the apical type, elevated levels of troponin and inflammatory markers, and higher prevalence of vascular disease. In a Firth bias-reduced penalized-likelihood logistic regression model apical type, left ventricular ejection fraction ≤30%, previous vascular disease, and a white blood cell count on admission >10×10 3 cells/μL emerged as independent predictors for thrombus formation or embolism. Conclusions: Intraventricular thrombus or embolism occur in 3.3% of patients in the acute phase of TTS. A simple risk score including clinical parameters associated with intraventricular thrombus formation or embolism identifies patients at increased risk. Clinical Trial Registration: URL: http://www.clinicaltrials.gov . Unique identifier: NCT01947621.

AbstractIntroductionOur research aim was to develop a novel clinimetric scale sensitive enough to detect disease progression in primary lateral sclerosis (PLS).MethodsA prototype of the PLS Functional Rating Scale (PLSFRS) was generated. Seventy‐seven participants with PLS were enrolled and evaluated at 21 sites that comprised the PLSFRS study group. Participants were assessed using the PLSFRS, Neuro‐Quality of Life (QoL), Schwab‐England Activities of Daily Living (ADL), and the Clinical Global Impression of Change scales. Participants completed telephone assessments at 12, 24, and 48 weeks after enrollment.ResultsThe PLSFRS demonstrated internal consistency as well as intrarater, interrater, telephone test‐retest reliability, and construct validity. Significant changes in disease progression were detected at 6 and 12 months; changes measured by the PLSFRS vs the ALSFRS‐R were significantly higher.DiscussionThe PLSFRS is a valid tool to assess the natural history of PLS in a shorter study period.

Abstract INTRODUCTION The management of glioblastoma (GBM) has changed over time and varies based on geographic location. Despite its universally fatal prognoses, it is unclear if GBM outcomes have changed over time, if they vary by geographic location, and differ based on type of intervention. As a result, we conducted a systematic review of the literature to identify the average survival differences of GBM patients across time, between different continents, and among various treatments. METHODS The systematic review of PubMed included glioblastoma, GBM, and survival. Inclusion criteria consisted of full-text titles with human subjects, GBM/Grade IV astrocytoma, age >18 years old, and with available survival data. RESULTS 9,162 articles were screened for survival data, 1728 were eligible, 405 complied with the inclusion criteria. Of the 405 studies, 179 (44.2%) were conducted in Europe, 151 (37.3%) in the Americas, 61 (15.1%) in Asia, 9 (2.2%) in Oceania, and 1 (0.2%) in Africa. Leading countries are the United States (33.1%), Germany (12.3%), and Italy (11.1%). Asia had the highest median survival (14.9 months), followed by Europe (13.2 months), and the United States (12.9 months) (P=0.003). Regarding treatment, survival was significantly higher after the introduction of the Stupp protocol (P< 0.001). Post-Stupp Studies had longer survival estimates (15.3 months, range: 3.8–29.6) than Pre-Stupp Studies (12.2 months, range: 2.3–28). In the included clinical trials (182), radiation (43.4%), temozolomide (25.3%), or other chemotherapies (24.2%) were the most common interventions. Clinical trial median survival estimates were significantly higher than all other studies (P< 0.017). Bevacizumab (19.3 months) and Temozolomide (15.9 months) had the longest recorded median survival estimates; while radiation (14 months), other chemotherapies, and carmustine (13.2 months) had the shortest (P=0.009). CONCLUSION This epidemiological study describes the current global state of GBM. Important differences regarding survival and treatment of patients with GBM were found.

Abstract INTRODUCTION The development of diabetes insipidus (DI) after pituitary adenoma resection is associated with worse post-surgical morbidity and longer hospital stay. Identification of clinical predictors of development of DI would allow for appropriate stratification of patients to optimize preoperative counseling and postoperative management. METHODS We conducted a retrospective review of 349 patients who underwent pituitary adenoma resection at Johns Hopkins Hospital between 2003 and 2017. We used unadjusted and adjusted logistic regression to identify predictors of developing DI. Factors which were associated with DI development (p< 0.1), were included in our multivariable model. Factors which remained associated with DI development were then used to develop a DI risk score. RESULT: 67 (19.2%) patients developed post-surgical DI. Patients who had symptoms of prolactinoma, surgery through one nare, or were on steroid treatment were more likely to develop DI. Conversely, patients who had unilateral cavernous sinus invasion were less likely to develop DI. We used these predictors to generate the DI risk score. Patients were assigned 1 point for each risk factor (symptoms of prolactinoma, steroids, or surgery through one nare) for developing DI, but 1 point was subtracted if they had a protective factor (unilateral cavernous sinus invasion). Patients with 0 points had a 10.7% probability of developing DI, patients with 1 point had a 18.5% probability of developing DI, patients with 2 points had a 41.2% probability of developing DI, and patients with 3 points had a 44.4% probability of DI. CONCLUSIONS We identified several predictors of DI development after pituitary adenoma resection, and used these to generate a DI risk score. The DI risk score could help stratify patients’ likelihood of postsurgical DI development, although validation through larger prospective multi-center studies are needed.

Abstract INTRODUCTION Repeat surgery after tumor recurrence after pituitary adenoma resection can be challenging due to formation of scar tissue and loss of surgical landmarks, which can lead to increased rates of postoperative complications. Identification of clinical predictors of tumor recurrence would allow for appropriate stratification of patients to optimize preoperative counseling and postoperative management. METHODS We conducted a retrospective review of 349 patients who underwent pituitary adenoma resection at Johns Hopkins Hospital between 2003 and 2017. We used unadjusted and adjusted logistic regression to identify predictors of tumor recurrence. Factors which were associated with tumor recurrence in univariable models (p< 0.1), were included in our multivariable model. Factors that remained significantly associated with tumor recurrence (p< 0.05) in our multivariable model were considered predictors of recurrence. RESULTS 59 (16.9%) patients developed tumor recurrence at the time of our study. Patients who had surgery through one nare, transcranial surgery, visual field deficit, larger tumor volume, bilateral cavernous sinus invasion, carotid artery invasion, and postoperative cerebral spinal fluid (CSF) leak were more likely to have tumor recurrence. Conversely, patients who are younger in age, had sphenoid packing, and gross total resection were less likely to have tumor recurrence. In our multivariable model, only age (adjusted odds ratio[aOR]: 0.96), surgery through one nare (aOR: 2.05), gross total resection(aOR: 0.21), and presence of CSF leak(aOR: 4.43) remained significantly associated with tumor recurrence. CONCLUSIONS We identified several predictors of tumor recurrence after pituitary adenoma resection. Notably, having gross total resection of the primary tumor had the most significant protective effect on tumor recurrence. Given the increased complication associated with repeat surgery, gross total resection should be attempted in all patients, if feasible. Patients with other predictors of tumor recurrence should be monitored more frequently to allow for early detection of recurrence to optimize treatment strategies.

Gestational trophoblastic neoplasia (GTN), a subset of gestational trophoblastic disease (GTD), occurs when tumors develop in the cells that would normally form the placenta during pregnancy. The NCCN Guidelines for Gestational Trophoblastic Neoplasia provides treatment recommendations for various types of GTD including hydatidiform mole, persistent post-molar GTN, low-risk GTN, high-risk GTN, and intermediate trophoblastic tumor.

Radiologically isolated syndrome (RIS), in which asymptomatic demyelinating-appearing lesions are detected incidentally on MRI, can be a pre-clinical form of multiple sclerosis (MS). In this study, we measured cerebellar volumes on 3D T1-weighted 3T MR images in 21 individuals with RIS and 38 age- and sex-matched healthy controls (HC). Normalized cerebellar white matter volume and the anterior cerebellar gray matter volume were significantly decreased in RIS compared to HC ( p = 0.003 and p = 0.005, respectively). Our findings support reports of regional brain atrophy in RIS prior to the development of a seminal attack related to inflammatory demyelination.

Background Left ventricular ( LV ) recovery in takotsubo syndrome ( TTS ) occurs over a wide‐ranging interval, varying from hours to weeks. We sought to investigate the clinical predictors and prognostic impact of recovery time for TTS patients. Methods and Results TTS patients from the International Takotsubo Registry were included in this study. Cut‐off for early LV recovery was determined to be 10 days after the acute event. Multivariable logistic regression was used to assess factors associated with the absence of early recovery. In‐hospital outcomes and 1‐year mortality were compared for patients with versus without early recovery. We analyzed 406 patients with comprehensive and serial imaging data regarding time to recovery. Of these, 191 (47.0%) had early LV recovery and 215 (53.0%) demonstrated late LV improvement. Patients without early recovery were more often male (12.6% versus 5.2%; P =0.011) and presented more frequently with typical TTS (76.3% versus 67.0%, P =0.040). Cardiac and inflammatory markers were higher in patients without early recovery than in those with early recovery. Patients without early recovery showed unfavorable 1‐year outcome compared with patients with early recovery ( P =0.003). On multiple logistic regression, male sex, LV ejection fraction <45%, and acute neurologic disorders were associated with the absence of early recovery. Conclusions TTS patients without early LV recovery have different clinical characteristics and less favorable 1‐year outcome compared with patients with early recovery. The factors associated with the absence of early recovery included male sex, reduced LV ejection fraction, and acute neurologic events. Clinical Trial Registration URL : http://www.clinicaltrials.gov . Unique identifier: NCT 01947621.

Pharmacologic stimulation of a G protein–coupled receptor preferentially expressed on fibroblasts reverses experimental lung and liver fibrosis.

Altered airway smooth muscle (ASM) mass and extracellular matrix (ECM) deposition in airways are characteristic features of remodeling in asthma. Increased ECM production modulates ASM cell proliferation and leads to airway remodeling. Our previous studies showed that ASM from patients with asthma exhibited increased expression of estrogen receptor (ER)‐β, which upon activation down‐regulated ASM proliferation, implicating an important role for estrogen signaling in airway physiology. There is no current information on the effect of differential ER activation on ECM production. In this study, we evaluated the effect of ER‐α vs. ER‐β activation on ECM production, deposition, and underlying pathways. Primary human ASM cells isolated from asthmatics and nonasthmatics were treated with E 2 , an ER‐α agonist [propylpyrazoletriol (PPT)], and an ER‐β agonist [WAY‐200070 (WAY)] with TNF‐α or platelet‐derived growth factor (PDGF) followed by evaluation of ECM production and deposition. Expression of proteins and genes corresponding to ECM were measured using Western blotting and quantitative RT‐PCR with subsequent matrix metalloproteinase (MMP) activity. Molecular mechanisms of ER activation in regulating ECM were evaluated by luciferase reporter assays for activator protein 1 (AP‐1) and NF‐κB. TNF‐α or PDGF significantly ( P < 0.001) increased ECM deposition and MMP activity in human ASM cells, which was significantly reduced with WAY treatment but not with PPT. Furthermore, TNF‐α‐ or PDGF‐induced ECM gene expression in ASM cells was significantly reduced with WAY ( P < 0.001). Moreover, WAY significantly down‐regulated the activation of NF‐κB( P < 0.001) and AP‐1 ( P < 0.01, P < 0.05) in ASM cells from asthmatics and nonasthmatics. Overall, we demonstrate differential ER signaling in controlling ECM production and deposition. Activation of ER‐β diminishes ECM deposition via suppressing the NF‐κB pathway activity and might serve as a novel target to blunt airway remodeling.—Ambhore, N. S., Kalidhindi, R. S. R., Pabelick, C. M., Hawse, J. R., Prakash, Y. S., Sathish, V. Differential estrogen‐receptor activation regulates extracellular matrix deposition in human airway smooth muscle remodeling via NF‐κB pathway. FASEB J. 33, 13935‐13950 (2019). www.fasebj.org