Borjabad A.,Columbia University |
Morgello S.,The Mount Sinai Medical Center |
Chao W.,Columbia University |
Kim S.-Y.,Korea Research Institute of Bioscience and Biotechnology |
And 4 more authors.
PLoS Pathogens | Year: 2011
Antiretroviral therapy (ART) has reduced morbidity and mortality in HIV-1 infection; however HIV-1-associated neurocognitive disorders (HAND) persist despite treatment. The reasons for the limited efficacy of ART in the brain are unknown. Here we used functional genomics to determine ART effectiveness in the brain and to identify molecular signatures of HAND under ART. We performed genome-wide microarray analysis using Affymetrix U133 Plus 2.0 Arrays, real-time PCR, and immunohistochemistry in brain tissues from seven treated and eight untreated HAND patients and six uninfected controls. We also determined brain virus burdens by real-time PCR. Treated and untreated HAND brains had distinct gene expression profiles with ART transcriptomes clustering with HIV-1-negative controls. The molecular disease profile of untreated HAND showed dysregulated expression of 1470 genes at p<0.05, with activation of antiviral and immune responses and suppression of synaptic transmission and neurogenesis. The overall brain transcriptome changes in these patients were independent of histological manifestation of HIV-1 encephalitis and brain virus burdens. Depending on treatment compliance, brain transcriptomes from patients on ART had 83% to 93% fewer dysregulated genes and significantly lower dysregulation of biological pathways compared to untreated patients, with particular improvement indicated for nervous system functions. However a core of about 100 genes remained similarly dysregulated in both treated and untreated patient brain tissues. These genes participate in adaptive immune responses, and in interferon, cell cycle, and myelin pathways. Fluctuations of cellular gene expression in the brain correlated in Pearson's formula analysis with plasma but not brain virus burden. Our results define for the first time an aberrant genome-wide brain transcriptome of untreated HAND and they suggest that antiretroviral treatment can be broadly effective in reducing pathophysiological changes in the brain associated with HAND. Aberrantly expressed transcripts common to untreated and treated HAND may contribute to neurocognitive changes defying ART. © 2011 Borjabad et al.
Bytzer P.,Copenhagen University |
Connolly S.J.,Hamilton Health Sciences |
Yang S.,Hamilton Health Sciences |
Ezekowitz M.,Jefferson Medical College and Lankenau Medical Center |
And 3 more authors.
Clinical Gastroenterology and Hepatology | Year: 2013
Background & Aims: Dabigatran is an oral and direct inhibitor of thrombin. In a study of patients with atrial fibrillation (the RE-LY trial), twice as many subjects given dabigatran reported dyspepsia-like symptoms compared with those given warfarin (controls). We analyzed data from this trial to quantify upper gastrointestinal nonbleeding adverse events (NB-UGI AEs). Methods: We analyzed the AE database from the RE-LY trial (18,113 subjects) and assigned NB-UGI AEs to 4 groups: those associated with gastroesophageal reflux (GERD), upper abdominal pain and dyspepsia, dysmotility, or gastroduodenal injury. We analyzed frequency, timing, and severity, and clinical variables associated with NB-UGI AEs. Results: NB-UGI AEs occurred in 16.9% of subjects given dabigatran and in 9.4% of controls (relative risk [RR], 1.81; 95% confidence interval [CI], 1.66%-1.97%; P < .001). Rates of AEs were not associated with the dose of dabigatran. Among subjects with any UGI symptom who were given dabigatran (n = 2045), symptoms were rated as mild in 46.3%, moderate in 44.8%, and severe in 8.9%; these values were similar to those of controls. GERD-associated NB-UGI AEs were most frequent among the 4 groups (compared with controls, RR, 3.71; 95% CI, 2.98%-4.62%; P < .001). Four percent of subjects stopped taking dabigatran because of NB-UGI AEs (most within 3 months of starting therapy), compared with 1.7% of controls (RR, 2.34; 95% CI, 1.90%-2.88%; P < .001). NB-UGI AEs slightly increased risk of major GI bleeding among subjects given dabigatran and controls (6.8% vs 2.3%, P < .001). Conclusions: Among patients given dabigatran for atrial fibrillation, NB-UGI AEs are generally mild or moderate; 4% stopped taking the drug over a median of 21.7 months. The greatest increase was in GERD-type NB-UGI AEs. These observations should guide management and prevention strategies. © 2013 AGA Institute.
Cavallaro P.,Mount Sinai School of Medicine |
Itagaki S.,The Mount Sinai Medical Center |
Seigerman M.,Mount Sinai School of Medicine |
Chikwe J.,Mount Sinai School of Medicine |
Chikwe J.,The Mount Sinai Medical Center
European Journal of Cardio-thoracic Surgery | Year: 2014
OBJECTIVES: The objective of this study was to compare the early outcomes of off-pump and on-pump surgeries in high-risk patient groups. METHODS: The outcomes of 83 914 high-risk patients undergoing off-pump or on-pump isolated coronary bypass surgery identified from the Nationwide Inpatient Sample from 2005 to 2010 were compared using propensity analysis. RESULTS: Off-pump surgery was associated with a significant reduction in stroke rates compared with on-pump surgery in propensitymatched patients ≥80 years (odds ratio [OR] 0.70, 95% confidence interval [CI] 0.52-0.93, P = 0.02), those with peripheral vascular disease (OR 0.53, 95% CI 0.36-0.77, P = 0.001) and those with aortic atherosclerosis (OR 0.30, 95% CI 0.13-0.72, P = 0.007). In these high-risk subgroups, off-pump surgery was associated with an absolute risk reduction in stroke rates of 0.5, 0.5 and 1.2%, respectively: The minimum number needed to treat to prevent one stroke is 200 patients. There was no significant difference in in-hospital mortality or the incidence of postoperative renal failure or respiratory failure between off-pump and on-pump surgeries in these patient subgroups, or in patients with preoperative renal failure, or chronic obstructive airways disease. CONCLUSIONS: High-risk patients undergoing coronary artery bypass surgery gain a short-term benefit from off-pump approaches due to a small absolute reduction in the risk of postoperative stroke.© The Author 2013.Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.
Rucker J.C.,The Mount Sinai Medical Center
Handbook of Clinical Neurology | Year: 2011
This chapter on lid function is comprised of two primary sections, the first on normal eyelid anatomy, neurological innervation, and physiology, and the second on abnormal eyelid function in disease states. The eyelids serve several important ocular functions, the primary objectives of which are protection of the anterior globe from injury and maintenance of the ocular tear film. Typical eyelid behaviors to perform these functions include blinking (voluntary, spontaneous, or reflexive), voluntary eye closure (gentle or forced), partial lid lowering during squinting, normal lid retraction during emotional states such as surprise or fear (startle reflex), and coordination of lid movements with vertical eye movements for maximal eye protection. Detailed description of the neurological innervation patterns and neurophysiology of each of these lid behaviors is provided. Abnormal lid function is divided by conditions resulting in excessive lid closure (cerebral ptosis, apraxia of lid opening, blepharospasm, oculomotor palsy, Horner's syndrome, myasthenia gravis, and mechanical) and those resulting in excessive lid opening (midbrain lid retraction, facial nerve palsy, and lid retraction due to orbital disease). © 2011 Elsevier B.V.
Mittnacht A.J.C.,The Mount Sinai Medical Center |
Hollinger I.,The Mount Sinai Medical Center
Annals of Cardiac Anaesthesia | Year: 2010
Fast-tracking in cardiac surgery refers to the concept of early extubation, mobilization and hospital discharge in an effort to reduce costs and perioperative morbidity. With careful patient selection, fast-tracking can be performed in many patients undergoing surgery for congenital heart disease (CHD). In order to accomplish this safely, a multidisciplinary coordinated approach is necessary. This manuscript reviews currently used anesthetic techniques, patient selection, and available information about the safety and patient outcome associated with this approach.
Droller M.J.,The Mount Sinai Medical Center
Urologic Oncology: Seminars and Original Investigations | Year: 2015
The fundamental responsibility of a journal editor is to assure that studies accepted for publication provide rigorous original scientific information and reviews that are considered important to the readership. The fundamental requirements of such reports from an editor's perspective include objectivity and transparency in each of the study design, implementation of investigation methods, acquisition of data, inclusive analysis and interpretation of results, appropriate application of statistical methods, presentation of outcomes in the context of a balanced and comprehensive review of relevant literature, and meaningful conclusions. In proceeding on these presumptions, editors then have the responsibility of obtaining rigorous, objective, and constructive reviews of these reports so that they can make an unbiased decision regarding their disposition. The fundamental objective in this is to enhance the ultimate scientific validity and value of the work if and when it is accepted for publication. Guidelines have been advanced by several organizations to identify how such editorial responsibilities can be fulfilled. These guidelines also pertain to investigators, authors, and sponsors of the studies, which the various reports and reviews describe. The present article reviews these guidelines as they relate to both industry-sponsored and investigator-initiated investigations and as relevant to the variety of reports that a scientific/medical journal such as Urologic Oncology: Seminars and Original Investigations receives for publication. © 2015 Elsevier Inc.
Gainsburg D.M.,The Mount Sinai Medical Center
Minerva Anestesiologica | Year: 2012
The anesthetic concerns of patients undergoing robotic-assisted laparoscopic radical prostatectomy (RALP) are primarily related to the use of pneumoperitoneum in the steep Trendelenburg position. This combination will affect cerebrovascular, respiratory and hemodynamic homeostasis. Possible non-surgical complications range from mild subcutaneous emphysema to devastating ischemic optic neuropathy. The anesthetic management of RALP patients involves a thorough preoperative evaluation, careful positioning on the operative table, managing ventilation issues, and appropriate fluid management. Close coordination between the anesthesia and surgical teams is required for a successful surgery. This review will discuss the anesthetic concerns and perioperative management of patients presenting for RALP. © 2012 Edizioni Minerva Medica.
De Los Reyes K.,The Mount Sinai Medical Center
Neurosurgery | Year: 2010
Deep brain stimulation (DBS) has become routine for the treatment of Parkinson's disease and essential tremor. Because both of these disorders are common in patients older than the age of 60, neurosurgeons are likely to encounter increasing numbers of patients who require DBS surgery but who already have another electronic medical implant such as a cardiac pacemaker/defibrillator or intrathecal infusion pump, raising the concern that one device might interfere with the performance of the other. Herein we report a modification of surgical technique resulting in the successful use of thalamic DBS to treat disabling essential tremor in a man with a previously implanted cochlear implant. INTERVENTION AND TECHNIQUE: The presence of the cochlear implant necessitated a number of modifications to our standard surgical technique including surgical removal of the subgaleal magnet that holds the receiver to the scalp and the use of computed tomography instead of magnetic resonance imaging to target the thalamus. More than a year after surgery, the patient is enjoying continued tremor suppression and an enhanced quality of life. The presence of the DBS device has not interfered with the proper functioning of his cochlear implant. DBS can be used successfully in patients with a previously implanted cochlear implant. The operating neurosurgeon should be aware of the limitations of intraoperative imaging and the need to coordinate with an otologic surgeon for maximum patient benefit.
Varghese R.,The Mount Sinai Medical Center |
Itagaki S.,The Mount Sinai Medical Center |
Anyanwu A.C.,The Mount Sinai Medical Center |
Trigo P.,The Mount Sinai Medical Center |
And 2 more authors.
European Journal of Cardio-thoracic Surgery | Year: 2014
OBJECTIVES: We set out to determine if intraoperative pre-bypass transoesophageal echocardiography could assist in predicting which patients are at greatest risk for systolic anterior motion (SAM) after mitral valve repair (MVR). METHODS: Three hundred and seventy-five consecutive patients who underwent reconstructive MVR surgery for degenerative disease were included. Data were collected using intraoperative echocardiographic images taken prior to the initiation of cardiopulmonary bypass. Based on the physiology of SAM, we postulated that 11 parameters could be potential risk factors for SAM: left ventricular ejection fraction (LVEF), left ventricular end-systolic dimension, left ventricular end-diastolic dimension (LVEDD), basal septal diameter (basal-interventricular septal diameter in diastole (IVDd)), mid-ventricular septal diameter (mid-IVDd), coaptation-septal distance (c-sept), anterior leaflet height, posterior leaflet height, aorto-mitral angle, mitral annular diameter and left atrial diameter. These parameters were measured and recorded by a blinded single operator. Independent predictors of SAM were identified using multiple logistic regression analysis. RESULTS: Of the 375 patients, 345 (92%) did not develop SAM (No-SAM group), while 30 (8%) developed intraoperative or postoperative SAM (SAM group). The mean age was 56.8 ± 12.8 and 56.7 ± 13.8 in the No-SAM and SAM groups, respectively. The incidence of fibroelastic deficiency, forme fruste and Barlow's disease was similar in both groups. All patients received a complete annuloplasty ring as part of the repair. There was no statistical difference in the mean ring size used in each group. EF was similar in the No-SAM (56.2% ± 8.1) and SAM (57.0% ± 9.2) P = 0.63) groups. Independent predictors of developing SAM after valve repair were: EDD <45mm [odds ratio (OR) 3.90; P = 0.028], aorto-mitral angle <120o (OR 2.74; P = 0.041), coaptation-septum distance <25mm (OR 5.09; P = 0.003), posterior leaflet height >15mm (OR 3.80; P = 0.012) and basal septal diameter ≥15mm (OR 3.63; P = 0.039). CONCLUSIONS: The risk for SAM can be predicted using intraoperative transoesophageal echocardiography. The combination of a smaller left ventricle, tall posterior leaflet, narrow aorto-mitral angle and enlarged basal septum significantly increases the risk for SAM. Knowing these parameters prior to valve repair can assist the surgeon in adjusting their repair technique to minimize the risk. © The Author 2013.
Zhadanov S.I.,The Mount Sinai Medical Center
Journal of Computer Assisted Tomography | Year: 2016
OBJECTIVE: Beyond fat suppression (FS), the efficacy of (fat-water separation or Dixon [FWD]) Dixon imaging in gadolinium-enhanced spine imaging has yet to be validated. This study evaluated enhanced opposed-phase (OP) and fat-only (FO) images along with water-only (WO; FS) images against traditional unenhanced techniques and rated the incremental value of in-phase imaging in patients with presumed neoplastic focal spine lesions. METHODS: A retrospective cohort study of 36 subjects with focal spine lesions imaged with FWD was evaluated qualitatively and quantitatively. RESULTS: Enhanced OP, WO, and FO images were of significant value in detection of osseous lesions, surpassing the lesion conspicuity with conventional techniques both qualitatively and quantitatively, although the impact of in-phase imaging was limited. Water-only imaging performed well for FS. CONCLUSIONS: Contrast-enhanced FO, WO, and OP outperform traditional techniques, providing reliable lesion characterization and highest conspicuity. In-phase imaging offered limited impact on the subjective assessment of enhancement. The added value and robustness of FWD, particularly the unique contrast provided by FO imaging, suggests consideration for routine use for postgadolinium spine imaging. Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved.