Jean-Michel Gracies

Hôpital Henri Mondor (Hôpitaux Universitaires Henri Mondor), Créteil, Île-de-France, France

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Publications (46)121.77 Total impact

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    ABSTRACT: Resistance from antagonistic muscle groups might be a crucial factor reducing function in chronic hemiparesis. The resistance due to spastic co-contraction might be reduced by botulinum toxin injections. We assessed the effects of abobotulinumtoxinA injection in the upper limb muscles on muscle tone, spasticity, active movement, and function. In this randomised, placebo-controlled, double-blind study, we enrolled adults (aged 18-80 years) at least 6 months after stroke or brain trauma from 34 neurology or rehabilitation clinics in Europe and the USA. Eligible participants were randomly allocated in a 1:1:1 ratio with a computer-generated list to receive a single injection session of abobotulinumtoxinA 500 U or 1000 U or placebo into the most hypertonic muscle group among the elbow, wrist, or finger flexors (primary target muscle group [PTMG]), and into at least two additional muscle groups from the elbow, wrist, or finger flexors or shoulder extensors. Patients and investigators were masked to treatment allocation. The primary endpoint was the change in muscle tone (Modified Ashworth Scale [MAS]) in the PTMG from baseline to 4 weeks. Secondary endpoints were Physician Global Assessment (PGA) at week 4 and change from baseline to 4 weeks in the perceived function (Disability Assessment Scale [DAS]) in the principal target of treatment, selected by the patient together with physician from four functional domains (dressing, hygiene, limb position, and pain). Analysis was by intention to treat. This study is registered with, number NCT01313299. 243 patients were randomly allocated to placebo (n=81), abobotulinumtoxinA 500 U (n=81), or abobotulinumtoxinA 1000 U (n=81). Mean change in MAS score from baseline at week 4 in the PTMG was -0·3 (SD 0·6) in the placebo group (n=79), -1·2 (1·0) in the abobotulinumtoxinA 500 U group (n=80; difference -0·9, 95% CI -1·2 to -0·6; p<0·0001 vs placebo), and -1·4 (1·1) in the abobotulinumtoxinA 1000 U group (n=79; -1·1, -1·4 to -0·8; p<0·0001 vs placebo). Mean PGA score at week 4 was 0·6 (SD 1·0) in the placebo group (n=78), 1·4 (1·1) in the abobotulinumtoxinA 500 U group (n=80; p=0·0003 vs placebo), and 1·8 (1·1) in the abobotulinumtoxinA 1000 U group (n=78; p<0·0001 vs placebo). Mean change from baseline at week 4 in DAS score for the principal target of treatment was -0·5 (0·7) in the placebo group (n=79), -0·7 (0·8) in the abobotulinumtoxinA 500 U group (n=80; p=0·2560 vs placebo), and -0·7 (0·7) in the abobotulinumtoxinA 1000 U group (n=78; p=0·0772 vs placebo). Three serious adverse events occurred in each group and none were treatment related; two resulted in death (from pulmonary oedema in the placebo group and a pre-existing unspecified cardiovascular disorder in the abobotulinumtoxinA 500 U group). Adverse events that were thought to be treatment related occurred in two (2%), six (7%), and seven (9%) patients in the placebo, abobotulinumtoxinA 500 U, and abobotulinumtoxinA 1000 U groups, respectively. The most common treatment-related adverse event was mild muscle weakness. All adverse events were mild or moderate. AbobotulinumtoxinA at doses of 500 U or 1000 U injected into upper limb muscles provided tone reduction and clinical benefit in hemiparesis. Future research into the treatment of spastic paresis with botulinum toxin should use active movement and function as primary outcome measures. Ipsen. Copyright © 2015 Elsevier Ltd. All rights reserved.
    The Lancet Neurology 09/2015; DOI:10.1016/S1474-4422(15)00216-1 · 21.90 Impact Factor

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    Marjolaine Baude · Emilie Hutin · Jean-Michel Gracies ·
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    ABSTRACT: Objective: To design a bidimensional facial movement measuring tool and study its reliability. Methods: We utilized the free video-analysis software Kinovea that can track preselected points during movements and measure two-point distances off-line. Three raters positioned facial markers on 10 healthy individuals and video-taped them during maximal bilateral contractions of frontalis, corrugator, orbicularis oculi, zygomaticus, orbicularis oris, and buccinator, on two occasions. Each rater also analyzed the first video twice, one week apart. For each muscle, intrarater reliability was measured by percent agreements (PA) and intraclass correlation coefficients (ICC) between two assessments of the same video one week apart and between assessments of two videos collected one week apart. Interrater reliability was measured by PA, ICC, and coefficients of variation (CV) between assessments of the first video-recording by the three raters. Results: Intrarater and interrater reliabilities were good to excellent for frontalis (PA and ICC > 70%; CV < 15%), moderate for orbicularis oculi, zygomaticus, and orbicularis oris, and poor for corrugator and buccinators. Discussion: Without formal prior training, the proposed method was reliable for frontalis in healthy subjects. Improved marker selection, training sessions, and testing reliability in patients with facial paresis may enhance reliability for orbicularis oculi, zygomaticus, and orbicularis oris.
    07/2015; 2015:812961. DOI:10.1155/2015/812961
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    Maud Pradines · Marjolaine Baude · Valentina Mardale · Emilie Hutin · Jean-Michel Gracies ·
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    ABSTRACT: Objective: To explore functional muscle lengthening following self-stretching programs within Guided Self-rehabilitation Contracts (GSC) in chronic spastic paresis. Design: Retrospective chart review Setting: Tertiary rehabilitation outpatient center Subjects: Sixteen patients (7F; age 40±8) with spastic paresis treated with GSC for at least one year. Intervention: Teaching of daily self-stretching postures within a GSC for soleus, gastrocnemius, hamstrings, vastus and rectus femoris muscles, maintained for 1 to 2 years. Outcome Measures: Functional muscle length (angle of arrest at slow speed, XV1) and coefficient of contracture (XN-XV1)/XN (XN, normal passive amplitude). Muscles were considered responders for functional lengthening if ΔXV1 exceeded 5° for soleus and gastrocnemius, and 10° for hamstrings, vastus and rectus femoris muscles. Results: In retrospect, coefficients of contracture were 0.12±0.03 (mean±SE) in the muscles for which stretch was not prescribed and 0.20±0.02 in muscles for which stretch was prescribed. The percent responders was greater in stretched than in non-stretched muscles after one and two years of GSC (p=0.025; p=0.035 respectively, Chi2). After one year, coefficients of contracture decreased by 18% in self-stretched vs 5% in non-self-stretched muscles (difference p=0.028, Mann Whitney). In individual muscles, raw functional lengthening with prescribed self-stretch for 1 year and 2 years was, respectively: +6°±4 and +9°±6 hamstrings, +4°±2 and +6°±2 in vastus muscles; +7°±6 and +13°±7.5 in rectus femoris, and +3°±3 at 1 year in soleus. Conclusion: Self-stretch within Guided Self-rehabilitation Contracts may produce measurable functional muscle lengthening in chronic hemiparesis, with clearer effects in proximal muscles. A prospective controlled study is required.
    Congress of Neurorehabilitation and Neural Repair, Maastricht; 05/2015
  • Maria Vinti · Nicolas Bayle · Emilie Hutin · David Burke · Jean-Michel Gracies ·
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    ABSTRACT: In spastic paresis, stretch applied to the antagonist increases its inappropriate recruitment during agonist command (spastic co-contraction). It is unknown whether antagonist stretch: (1) also affects agonist recruitment; (2) alters effort perception. We quantified voluntary activation of ankle dorsiflexors, effort perception, and plantar flexor co-contraction during graded dorsiflexion efforts at two gastrocnemius lengths. Eighteen healthy (age 41 ± 13) and 18 hemiparetic (age 54 ± 12) subjects performed light, medium and maximal isometric dorsiflexion efforts with the knee flexed or extended. We determined dorsiflexor torque, Root Mean Square EMG and Agonist Recruitment/Co-contraction Indices (ARI/CCI) from the 500 ms peak voluntary agonist recruitment in a 5-s maximal isometric effort in tibialis anterior, soleus and medial gastrocnemius. Subjects retrospectively reported effort perception on a 10-point visual analog scale. During gastrocnemius stretch in hemiparetic subjects, we observed: (1) a 25 ± 7 % reduction of tibialis anterior voluntary activation (maximum reduction 98 %; knee extended vs knee flexed; p = 0.007, ANOVA); (2) an increase in dorsiflexion effort perception (p = 0.03, ANCOVA). Such changes did not occur in healthy subjects. Effort perception depended on tibialis anterior recruitment only (βARITA = 0.61, p < 0.01) in healthy subjects (not on gastrocnemius medialis co-contraction) while it depended on both tibialis anterior agonist recruitment (βARITA = 0.41, p < 0.001) and gastrocnemius medialis co-contraction (βCCIMG = 0.43, p < 0.001) in hemiparetic subjects. In hemiparesis, voluntary ability to recruit agonist motoneurones is impaired-sometimes abolished-by antagonist stretch, a phenomenon defined here as stretch-sensitive paresis. In addition, spastic co-contraction increases effort perception, an additional incentive to evaluate and treat this phenomenon.
    Journal of Neural Transmission 02/2015; 122(8). DOI:10.1007/s00702-015-1379-3 · 2.40 Impact Factor

  • Toxicon 01/2015; 93:S30. DOI:10.1016/j.toxicon.2014.11.101 · 2.49 Impact Factor

  • Toxicon 01/2015; 93:S29-S30. DOI:10.1016/j.toxicon.2014.11.100 · 2.49 Impact Factor
  • Christophe Duret · Emilie Hutin · Laurent Lehenaff · Jean-Michel Gracies ·
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    ABSTRACT: Purpose: Upper limb robot-assisted rehabilitation is a highly intensive therapy, mainly recommended after stroke. Whether robotic therapy is suitable for subacute patients with severe impairments including cognitive disorders is unknown. This retrospective study explored factors impacting on motor performance achieved in a 16-session robotic training combined with standard rehabilitation. Methods: Seventeen subacute inpatients (age 53 ± 18; 49 ± 26 days post-stroke) were assessed at baseline using upper extremity motor impairments scales, Functional Independence Measure, aphasia and neglect scores. Number of movements and robotic assistance were compared between Session 2 (S2), 8 (8) and 16 (S16), Motricity Index between pre and post-treatment. Correlation analyses explored predictors of motor performance. Results: Overall, number of movements and Motricity Index increased significantly while robot-assistance decreased. The mean number of movements per session correlated positively with baseline motor capacities but not with age, aphasia and neglect. However, the increase in Motricity index correlated negatively with baseline Motricity index and the increase in the number of movements correlated negatively with the number of movements at S2. Conclusion: High intensity robot-assisted training may be associated with motor improvement in subacute hemiparesis. More severely impaired patients may derive greater benefit from robot-assisted training; age, aphasia and neglect do not represent exclusion criteria.
    Restorative neurology and neuroscience 11/2014; 33(1). DOI:10.3233/RNN-140418 · 2.49 Impact Factor

  • Edited by EdiErmess, 07/2014; , ISBN: 9788870514117

  • Muscle & Nerve 05/2014; 49(5). DOI:10.1002/mus.24139 · 2.28 Impact Factor
  • Jean-Michel Gracies · Nicolas Bayle · Sarah Goldberg · David M Simpson ·
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    ABSTRACT: To determine the efficacy and safety of 2 doses of botulinum toxin type B (rimabotulinumtoxinB, BoNT/B) in spastic upper limb muscles. Randomized, double-blind, placebo-controlled trial with a 3-month follow-up SETTING: Tertiary care center PARTICIPANTS: Referred sample of 24 adult hemiparetic patients with disabling elbow flexor overactivity after stroke or traumatic brain injury. Injection of 10,000U of rimabotulinumtoxinB (fixed 2500U dose into elbow flexors; n=8), 15,000U (5000U into elbow flexors; n =8), or placebo (n=8), into overactive upper limb muscles selected as per investigator's discretion. At 1 month post-injection, active range of elbow extension (goniometry; primary outcome); active upper limb function (Modified Frenchay Scale, MFS); subjective global self-assessment (GSA) of arm pain, stiffness, and function; rapid alternating elbow flexion-extension movement frequency over the maximal range; elbow flexor spasticity grade and angle (Tardieu), and tone (Ashworth). No adverse effects were associated with either BoNT/B dose. Both doses improved active elbow extension vs placebo (+8.3°, 95%CI [1.1-15.5°], p=0.028, ANCOVA). The high dose of BoNT/B also improved subject-perceived stiffness (p=0.005) and the composite pain, stiffness and function GSA (p=0.017), effects that persisted 3 months from injection. No MFS change was demonstrated although subjects with baseline MFS <70/100 seemed more likely to benefit from BoNT/B. In this short-term study, BoNT/B up to 15,000U into spastic upper limb muscles including elbow flexors, was well tolerated and improved active elbow extension and subject-perceived stiffness.
    Archives of physical medicine and rehabilitation 04/2014; 95(7). DOI:10.1016/j.apmr.2014.03.016 · 2.57 Impact Factor

  • Clinical neurophysiology: official journal of the International Federation of Clinical Neurophysiology 12/2013; 125(7). DOI:10.1016/j.clinph.2013.11.023 · 3.10 Impact Factor
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    ABSTRACT: Introduction: In this study of spastic hemiparesis we evaluated cocontraction during sustained agonist/antagonist efforts, before and after botulinum toxin (BoNT) injection in 1 agonist. Methods: Nineteen hemiparetic subjects performed maximal isometric elbow flexion/extension efforts with the elbow at 100° (extensors stretched). Using flexor and extensor surface electromyography we calculated agonist recruitment/cocontraction indices from 500-ms peak voluntary agonist recruitment, before and 1 month after onabotulinumtoxinA injection (160 U) into biceps brachii. Results: Before injection, agonist recruitment and cocontraction indices were higher in extensors than flexors [0.74 ± 0.15 vs. 0.59 ± 0.10 (P < 0.01) and 0.43 ± 0.25 vs. 0.25 ± 0.13 (P < 0.05), respectively]. Biceps injection decreased extensor cocontraction index (-35%, P < 0.05) while increasing flexor agonist recruitment and cocontraction indices. Conclusions: In spastic hemiparesis, stretch may facilitate agonist recruitment and spastic cocontraction. In the non-injected antagonist, cocontraction may be reduced by enhanced reciprocal inhibition from a more relaxed, and therefore stretched, agonist, or through decreased recurrent inhibition from the injected muscle.
    Muscle & Nerve 12/2012; 46(6). DOI:10.1002/mus.23427 · 2.28 Impact Factor
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    ABSTRACT: Objective: Spastic co-contraction is a misdirected supraspinal command in spastic paresis. We quantified the influence of effort and gastrocnemius stretch on plantar flexor co-contraction and torque during dorsiflexion efforts in hemiparetic and healthy subjects. Methods: Eighteen healthy and 18 hemiparetic subjects produced "light", "medium" and "maximal" isometric dorsi- and plantar flexion efforts in two gastrocnemius positions, stretched (knee extended) and slack (knee flexed), ankle at 90°. Measuring ankle torque and soleus and medial gastrocnemius surface EMG, we calculated the co-contraction index (CCI) as the ratio of the EMG root mean square (RMS) from the muscle acting as antagonist over its RMS when acting as agonist in a maximal effort, in each knee position. Results: Co-contraction was abnormally high in hemiparetic subjects at all effort levels, e.g. for soleus in the knee extended position (CCI(SO) 0.37±0.08 in hemiparesis vs 0.18±0.02 in healthy subjects, p<0.05). In hemiparetic subjects knee extended, dorsiflexion torque, (i) was reversed or canceled in 26% trials; and (ii) correlated negatively with plantar flexor CCI. Significance: Major dynamometric impact of co-contraction with stretched position of the cocontracting muscle may justify muscle length modifications (e.g. through aggressive stretch programs) to improve function in spastic paresis.
    Clinical neurophysiology: official journal of the International Federation of Clinical Neurophysiology 10/2012; 124(3). DOI:10.1016/j.clinph.2012.08.010 · 3.10 Impact Factor
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    Emilie Hutin · Didier Pradon · Franck Barbier · Bernard Bussel · Jean-Michel Gracies · Nicolas Roche ·
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    ABSTRACT: Gait training at fast speed has been suggested as an efficient rehabilitation method in hemiparesis. We investigated whether maximal speed walking might positively impact inter-segmental coordination in hemiparetic subjects. We measured thigh-shank and shank-foot coordination in the sagittal plane during gait at preferred (P) and maximal (M) speed using the continuous relative phase (CRP), in 20 healthy and 27 hemiparetic subjects. We calculated the root-mean square (CRP(RMS)) and its variability (CRP(SD)) over each phase of the gait cycle. A small CRP(RMS) indicates in-phasing, i.e. high level of synchronization between two segments along the gait cycle. A small CRP(SD) indicates high stability of the inter-segmental coordination across gait cycles. Increase from preferred to maximal speed was 57% in healthy and 49% in hemiparetic subjects (difference NS). In healthy subjects, the main change was shank-foot in-phasing at stance (CRP(Shank-Foot/RMS), P, 98±10; M, 67±12, p<0.001). In hemiparetic subjects, we also found shank-foot in-phasing at late stance bilaterally (non-paretic CRP(Shank-Foot/RMS), P, 37±9; M, 29±8, p<0.001; paretic CRP(Shank-Foot/RMS), P, 38±13; M, 32±12, p<0.001), and thigh-shank in-phasing at mid-stance in the non-paretic limb (CRP(Thigh-Shank/RMS), P, 57±9; M, 49±9, p<0.001). CRP(Thigh-Shank) variability diminished in the paretic limb (CRP(Thigh-Shank/SD), P, 18.3±6.3; M, 16.1±5.2, p<0.001). During gait velocity increase in hemiparesis, there is improvement of thigh-shank coordination stability in the paretic limb and of shank-foot synchronization at late stance bilaterally, which optimizes the propulsive phase similarly to healthy subjects. These findings may add incentive for rehabilitation clinicians to explore maximal velocity gait training in hemiparesis.
    Gait & posture 04/2012; 36(2):205-11. DOI:10.1016/j.gaitpost.2012.02.016 · 2.75 Impact Factor
  • Marjolaine Baude · Svetlana Scripcaru · Diane Lafosse · Emilie Hutin · Jean-Michel Gracies ·

    Revue Neurologique 04/2012; 168:A100. DOI:10.1016/j.neurol.2012.01.255 · 0.66 Impact Factor
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    ABSTRACT: To examine the safety and efficacy of onabotulinumtoxinA (Botox) for plantarflexor overactivity following stroke. Double-blind randomized controlled trial, open-label extension phase. Neurology rehabilitation facilities. Eighty-five subjects with lower limb hypertonia received 200 U (n = 28) or 300 U (n = 28) of onabotulinumtoxinA or saline (n = 29) injection. Plantarflexor Ashworth scores at 12 weeks post injection and adverse events. Secondary measures: self-reported spasm frequency and pain, physician rating of hypertonia severity, gait quality and active dorsiflexion. Differences were not seen between onabotulinumtoxinA groups; hence data were pooled. Incidence of adverse events was not different between groups (P = 0.61). Reduction in hypertonia was not different between groups at 12 weeks (P = 0.53); however for subjects with Ashworth scores of >3 at baseline, 14/31 in the onabotulinumtoxinA group demonstrated a reduction of >1 grade versus 1/17 receiving placebo injection (P = 0.01). Overall, onabotulinumtoxinA-injected subjects demonstrated significantly greater improvement in spasm frequency (22/54 versus 4/29, P = 0.01), pain reduction (8/54 versus 1/29, P = 0.02), active dorsiflexion (8/54 versus 1/29 P = 0.03) and gait quality (17/54 versus 6/29, P = 0.02) than controls. In the open-label phase, a second onabotulinumtoxinA injection was associated with greater hypertonia reduction (P = 0.005) and gait quality (P = 0.002) compared with single injection. OnabotulinumtoxinA injection for ankle flexor overactivity after stroke was safe and well tolerated but did not alter local spasticity at 12 weeks; it did reduce spasms and improve gait quality. There were no detectable differences between higher and lower doses. A second injection may be associated with greater change.
    Clinical Rehabilitation 02/2012; 26(9):787-97. DOI:10.1177/0269215511432016 · 2.24 Impact Factor
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    ABSTRACT: Consistent with the hypothesis that dopamine is implicated in the processing of salient stimuli relevant to the modification of various behavioral responses, Parkinson's disease is associated with emotional blunting. To address the hypothesis that emotional attention and memory are modulated by dopaminergic neurotransmission in Parkinson's disease, we assessed 15 nondemented patients with Parkinson's disease while on and off dopaminergic medication and 15 age-matched healthy controls. Visual stimuli were presented, and recognition was used to assess emotional memory. Response latency was used as a measure of emotional attention modulation. Stimuli were varied based on valence (pleasant, neutral, and unpleasant) and arousal (high and low) dimensions. Controls had significantly better memory for positive than negative stimuli, whereas patients with Parkinson's disease tested off medication had significantly better memory for negative than positive items. This negativity bias was lost when they were tested while on dopaminergic medication. Reaction times in patients with Parkinson's disease off medication were longer than in healthy controls and, paradoxically, were even longer when on medication. Further, although both healthy controls and patients with Parkinson's disease in the "off" state had arousal-induced prolongation of reaction time, this effect was not seen in patients with Parkinson's disease on medication. These data indicate that dopaminergic neurotransmission is implicated in emotional memory and attention and suggest that dopamine mediates emotional memory via the valence dimension and emotional attention via arousal. Furthermore, our findings suggest that emotional changes in Parkinson's disease result from the effects of both the disease process and dopaminergic treatment.
    Movement Disorders 08/2011; 26(9):1677-83. DOI:10.1002/mds.23728 · 5.68 Impact Factor
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    ABSTRACT: Whereas aging affects cognitive and psychomotor processes negatively, the impact of aging on emotional processing is less clear. Using an "old-new" binary decision task, we ascertained the modulation of response latencies after presentation of neutral and emotional pictures in "young" (M = 27.1 years) and "young-old" adults with a mean age below 60 (M = 57.7 years). Stimuli varied on valence (pleasant, neutral, and unpleasant) and arousal (high and low) dimensions. Young-old adults had significantly longer reaction times. However, young and young-old adults showed the exact same pattern of response time modulation by emotional stimuli: Response latencies were longer for high-arousal than for low-arousal pictures and longer for negative than for positive or neutral stimuli. This result suggests that the specific effects of implicitly processed emotional valence and arousal information on behavioral response time are preserved in young-old adults despite significant age-related psychomotor decline.
    The International journal of neuroscience 05/2011; 121(8):430-6. DOI:10.3109/00207454.2011.568656 · 1.52 Impact Factor

Publication Stats

1k Citations
121.77 Total Impact Points


  • 2010-2015
    • Hôpital Henri Mondor (Hôpitaux Universitaires Henri Mondor)
      • Service de Réeducation Neurolocomoteur
      Créteil, Île-de-France, France
  • 2012
    • Université Paris-Est Créteil Val de Marne - Université Paris 12
      Créteil, Île-de-France, France
  • 2008-2012
    • L’Institut Régional de Médecine Physique et de Réadaptation
      Nancy, Lorraine, France
  • 2007-2011
    • Mount Sinai School of Medicine
      • Department of Neurology
      Manhattan, New York, United States
  • 2000-2009
    • Mount Sinai Medical Center
      New York City, New York, United States