Mount Sinai Medical Center Research Articles

Creating a Center for Nursing Research and Education in a Major Academic Medical Center

Mount Sinai Medical Center (MSMC) in New York City has long recognized the value of nurses and nursing. The hospital established one of the first nurse training schools in the United States in 1881. The nursing staff has continued its distinguished reputation in the healthcare community. In 2004, Mount Sinai earned designation as a Magnet® hospital by the American Nurses Credentialing Center (ANCC). And in 2009, Mount Sinai became the first full-service hospital in New York City to earn redesignation of the prestigious ANCC Magnet Award for an additional 4 years, from 2009 to 2013. Magnet designation is considered the gold standard for nursing excellence—only 8% of hospitals in the United States have earned this designation.

Prognostic Significance Of TP53mutations and Single Nucleotide Polymorphisms In Acute Myeloid Leukemia

BackgroundThe response to treatment and overall survival (OS) of patients with acute myeloid leukemia (AML) is variable, with a median OS ranging from several months to more than 10 years. Age at diagnosis, performance status (PS), and karyotype expression have long been established in prognostication. Loss of TP53, a tumor suppressor gene located on the short arm of chromosome 17, is one of the most frequent genetic abnormalities in human cancer and is one of the more promising prognostic markers for AML. Studies have shown that TP53 mutations are present in 5-25% of all AML patients, in 70% of those with complex karyotypes, and are associated with old age, chemotherapy resistance, and worse OS. Single nucleotide polymorphisms (SNPs), changes in DNA seen in an appreciable amount of the population, have been examined in AML and studies have suggested a possible correlation with worse outcomes. Using genetic sequencing, we set out to look at our own experience with AML, and hypothesized TP53mutations and SNPs would mimic the literature, occurring in a minority of patients, and conferring a worse OS. MethodsWe performed a pilot study of randomly selected, newly diagnosed AML patients at Mount Sinai Medical Center, diagnosed from 2005-2008 (n =10). Immunohistochemical (IHC) analysis of bone marrows and peripheral blood smears was assessed via DO-1 antibody on paraffin embedded tissue. Conventional cytogenetic analyses were performed on short-term cultured bone marrow and peripheral blood cells with the use of the GTG-banding technique. TP53PCR sequencing was performed using DNA from bone marrow smears using the Sanger sequencing platform and resolved by capillary electrophoresis. Analysis was performed using Mutation Surveyor software with confirmation of the variants using the COSMIC and dbSNP databases. Descriptive frequencies and median survivals were calculated for demographic information, prognostic factors, and treatment variables. A univariate analysis was performed. ResultsThe majority of patients in our pilot study were older than age 60 (80%), male (60%), Hispanic (60%), and had a poor PS (ECOG 2-3: 60%). Most patients had de-novo AML (50%) with an intermediate (50%) non-complex (70%) karyotype and a TP53 P72R SNP (50%). Fewer than half of these patients harbored TP53 mutations (40%). There was no significant difference in OS based on sex, AML history, risk-stratified karyotype, or TP53 mutation. There was a trend toward improved survival among patients younger than age 60 (11, 4 mo, p = 0.09), of Hispanic ethnicity (8, 1 mo, p = 0.11), and those not harboring P72R (8, 2, p = 0.10). There was a significant improvement in survival among patients with a better PS (28, 4 mo, p = 0.01) and those who did not have a complex karyotype (8, 1 mo, p = 0.03). Among patients with a TP53-mutation, there were a larger number of individuals who were younger than age 60 (25.0, 16.7%), who were male (75.0, 50.0%), had a good performance status (ECOG 0-1: 50.0, 16.7%), had de-novo AML (50.0, 66.7%), and who had an adverse karyotype (50.0, 33%). Patients with a P72R SNP were more often male (80, 40%) and had a worse PS (ECOG 2-3: 80, 40%) with AML secondary to MDS (60, 20%) and a complex karyotype (40, 0%). The most commonly observed TP53 mutation was a missense N310K (40%) and the most commonly observed SNP was P72R (100.0%). Patients with more than one TP53mutation had a worse clinical course than those with only a single mutation. ConclusionOur study demonstrated that poor PS and the presence of a complex karyotype were associated with a decreased OS. TP53 mutations were relatively uncommon, occurring more frequently in male patients with an adverse karyotype. Although there was no significant difference in survival between TP53 mutated and un-mutated patients, there was a trend toward worse OS among patients with a specific SNP. These results suggest that different TP53mutations and SNPs should not be treated the same, and that some may confer a worse prognosis than others. Larger studies are needed to validate these findings.Table 1PatientMutationSNPKaryotype and Gene AbnormalitiesOS (mo.)1-P72RTrisomy 8, deletion chromosome 16, trisomy 22, trisomy 9, CBFB gene rearrangement12P89SP72RUnknown43-P72RDeletion chromosome 20, trisomy 6, trisomy 22, isochromosome 21q, trisomy 11, MLL gene rearrangement14-P72RNormal115V272G-Normal48-P72R6C238G-inv(3), deletion chromosome 52N310K-7N310K-t(1,2), deletion chromosome 528 Disclosures:No relevant conflicts of interest to declare.

Economic and Safety Implications of Introducing Fast Tracking in Congenital Heart Surgery

Lawrence, Emily J.*; Nguyen, Khanh†; Morris, Shaine A.*; Hollinger, Ingrid‡; Graham, Dionne A.§∥; Jenkins, Kathy J.§∥; Bodian, Carol‡; Lin, Hung-Mo¶; Gelb, Bruce D.#; Mittnacht, Alexander J. C.‡ Author Information

Introduction: 2012 Daniel H. Wagner Prize for Excellence in Operations Research Practice

Competition for the 2012 Daniel H. Wagner Prize for Excellence in Operations Research Practice provided the six finalist papers featured in this special issue of Interfaces. The prestigious Wagner Prize—awarded for achievement in implemented operations research and advanced analytics—emphasizes quality and originality of mathematical models along with clarity of written and oral exposition. A team of OR researchers from the University of Southern California collaborated with U.S. Coast Guard personnel to win the competition with their novel approach to scheduling security patrols at U.S. ports. Of the remaining five finalists, three were from the field of health applications, having performed their work at the Duke Cancer Institute (nurse scheduling), the Mount Sinai Medical Center (hospital-bed assignment), and the Rush University Medical Center (cancer treatment); one focused on safety stock optimization; and the last dealt with the redesign of Philadelphia’s voting districts.

Automated Bed Assignments in a Complex and Dynamic Hospital Environment

Bed management, an important function of any hospital, has a major impact on patient care, patient flow, patient and staff satisfaction, and ultimately on the hospital’s operating margin. A key challenge in bed management is optimizing the bed-assignment process in a complex and dynamic operating environment. Efficient bed assignment requires the merging of clinical information, hospital operations information, interdependencies between units, and real-time information on patients, resources, and workflows. We have developed analytical decision support tools with embedded mathematical models to periodically recommend bed-patient assignments. Using an innovative mixed-integer goal-programming modeling approach, we are able to accommodate the multiple goals and complex operating rules of different hospitals. We implemented and hosted our prototype bed-assignment solution as a cloud-based application for Mount Sinai Medical Center in New York.

Follow-up Study of Atypical Diagnosis in Endoscopic Ultrasound-guided Fine Needle Aspiration of the Pancreas – A Decade of Experience from The Mount Sinai Medical Center

Follow-up Study of Atypical Diagnosis in Endoscopic Ultrasound-guided Fine Needle Aspiration of the Pancreas – A Decade of Experience from The Mount Sinai Medical Center

Annual NESPS Edition of Annals of Plastic Surgery

From the Mount Sinai Medical Center, New York, NY. Received June 11, 2013, and accepted for publication, after revision, June 11, 2013. Conflicts of interest and sources of funding: none declared. Reprints: Peter J. Taub, MD, FACS, FAAP, Mount Sinai Medical Center, New York, NY. E-mail: [email protected].

Elderly-Inpatient Care Model Delivered Mixed Results

Elderly-Inpatient Care Model Delivered Mixed Results

Neurological Complications of Intrathecal Methotrexate: A Case Report

PM&RVolume 5, Issue 9S p. S182-S182 General Rehabilitation Neurological Complications of Intrathecal Methotrexate: A Case Report Geet Paul MD, Geet Paul MD Mount Sinai Medical Center, New York, NY, United StatesSearch for more papers by this authorLauren M. Terranova DO, Lauren M. Terranova DO Mount Sinai Medical Center, New York, NY, United StatesSearch for more papers by this authorKathy Aligene MD, Kathy Aligene MD Mount Sinai Medical Center, New York, NY, United StatesSearch for more papers by this authorJeffrey S. Fine MD, Jeffrey S. Fine MD Mount Sinai Medical Center, New York, NY, United StatesSearch for more papers by this author Geet Paul MD, Geet Paul MD Mount Sinai Medical Center, New York, NY, United StatesSearch for more papers by this authorLauren M. Terranova DO, Lauren M. Terranova DO Mount Sinai Medical Center, New York, NY, United StatesSearch for more papers by this authorKathy Aligene MD, Kathy Aligene MD Mount Sinai Medical Center, New York, NY, United StatesSearch for more papers by this authorJeffrey S. Fine MD, Jeffrey S. Fine MD Mount Sinai Medical Center, New York, NY, United StatesSearch for more papers by this author First published: 17 September 2013 https://doi.org/10.1016/j.pmrj.2013.08.144Citations: 1Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article.Citing Literature Volume5, Issue9SSeptember 2013Pages S182-S182 RelatedInformation

EPILEPSY, DEPRESSION AND ANXIETY DISORDERS: A COMPLEX RELATION WITH SIGNIFICANT THERAPEUTIC IMPLICATIONS FOR THE THREE CONDITIONS

Andres M. Kanner is a senior attending physician at the department of Neurology and Director of the Comprehensive Epilepsy Center at the University of Miami, Miller School of Medicine, which...

Impact of vascular closure with the pre-closure technique on adverse events in patients undergoing transfemoral balloon aortic valvuloplasty: results from a single-center registry

Absrac Caegor 20. CI - Valvular Hear seasereseao umber 2533-319Auhors Brian P. ONeill, Vikas Singh, Jennifer Yu, David Knopf, Usman Baber, Claudia Martinez, Carlos Alfonso, Jason Kovacic, George Dangas, Evan Jacobs, Annapoorna Kini, Roxana Mehran, Samin Sharma, Pedro Martinez-Clark, Samantha Sartori, Alan Heldman, William ONeill, Mauricio Cohen, University of Miami Miller School of Medicine, Miami, FL, USA, Mount Sinai Medical Center, New York, NY, USABackground: Ischemc ad bleedg comlcaos, or e adverse clcal eves (ACE), are commo followg rasfemoral balloo aorc valvulolas (BAV). The mac of suure-medaed vascular closure o ACE hs seg s o ow.Methods: We coduced a rerosecve revew of 428 cosecuve aes who uderwe BAV wh large sheahs (10-13 Frech) over a 6-ear erod a wo hgh-volume academc ceers. Vascular closure was erformed usg he roGlde (Abbo Vascular) devce. ACE was deied as he comose of major bleedg ad major adverse clcal eves (MACE). All eves were adjudcaed b a deede CEC who were blded o ahromb use.Results: re-closure was erformed 269 (62.8%) of aes. Whle bvalrud was used more frequel hose wh re-closure (60.6% vs. 37.7%, <0.001), a hsor of ror BAV (11.1% vs. 3.6%, =0.04) ad erheral vascular dsease (30.7% vs. 19.7%, =0.01) was more commo hose o udergog re-closure (=159, 37%). Oher clcal ad demograhc feaures were well balaced bewee grous. Vascular closure was assocaed wh a sgica reduco ACE (Fgure). Resuls remaed sgica afer adjusg for basele dffereces ad bvalrud use (OR 0.38, 95% CI 0.21 - 0.68; =0.001).Conclusions: Our sud suggess ha suure-medaed vascular closure resuls a subsaal reduco ACE afer rasfemoral BAV. Large radomed clcal rals should be coduced o coirm our resuls.

Interview: Novel insights into renal denervation

Stephen Worthley speaks to Caroline Telfer, Assistant Commissioning Editor Professor Stephen Worthley graduated in Medicine at the University of Adelaide (Australia). His training included his cardiology fellowship at the Royal Adelaide Hospital, his PhD at the Mount Sinai Medical Center in New York (USA), and postdoctoral research and interventional fellowship at Monash Medical Centre (Australia). He established the first dedicated Cardiac Computed Tomography and Magnetic Resonance units in the Asia Pacific region, as well as leading the Cardiovascular Research Centre (University of Adelaide) as the Helpman Professor of Cardiovascular Medicine, a position he has held since 2004. He has published over 150 manuscripts and five book chapters, and coedited a cardiovascular textbook. He leads a number of novel international multicenter cardiovascular therapy trials, and his clinical and research expertise spans natriuretic peptide and stem cell therapies though to transcatheter valve implantation and renal ar...

Clinical Presentation and Outcomes of Inflammatory Bowel Disease Patients Admitted to the Intensive Care Unit

Disease severity, immunosuppression, and malnutrition may impact morbidity and mortality of the critically ill patient with inflammatory bowel disease (IBD). The aim of this study was to identify potential predictive factors for mortality among IBD patients requiring admission to an intensive care unit (ICU). All patients with an admitting diagnosis of ulcerative colitis or Crohn's disease presenting to the ICU at the Mount Sinai Medical Center from 2003 to 2008 were retrospectively analyzed. Data regarding IBD-specific features, medications, and surgical outcomes were collected as well as ICU-related morbidity and 30-day mortality. Ninety-five patients were admitted to the ICU out of a total of 6663 IBD-related hospital admissions with an overall 30-day mortality rate of 18.9%. The annual number of ICU admissions of all hospitalized IBD patients increased from 0.1% in 2003 to 2.6% of admissions in 2008. ICU-related variables associated with increased mortality included mechanical ventilation (P=0.0002), vasopressor requirement (P=0.0002), severe sepsis (P=0.0005), acute kidney injury (P=0.001), Acute Physiology and Chronic Health Evaluation II scores (P ≤ 0.0001), hypoalbuminemia (P=0.036), and thromboembolism (P=0.046). On multivariate analysis, elevated Acute Physiology and Chronic Health Evaluation II scores were the only independent predictor of mortality. Although the overall number of ICU admissions among IBD patients was low, the annual incidence rates of admissions are increasing. This patient subgroup had significant in-hospital morbidity and 30-day mortality. Earlier identification of potential risk factors leading to poorer outcome, particularly within the first 24 hours of ICU admission, may impact the triage and subsequent management of these critically ill patients.

Donor and Recipient Factors Predicting Time to Graft Failure Following Orthotopic Liver Transplantation: A Transplant Risk Index

IntroductionMuch of the success of a transplant depends on appropriate matching of donor to recipient. MethodsWe validated the Donor Risk Index formula (DRI) using Mount Sinai Medical Center's 10-year cohort of over 1000 transplants. ResultsThe DRI was significantly associated to graft failure with a relative risk (RR) of 1.32. Our cohort had an average DRI of 2.6 with survival of 83% at 3 months, 79% at 1 year, and 70% at 3 years. The low rate of graft failure at a high DRI implies that there are other factors important in transplant pairing that are not considered in the DRI model. To determine these variables and quantify their importance, we constructed a Transplant Risk Index by identifying recipient and donor variables not captured in United Network for Organ Sharing (UNOS) that significantly correlated to graft failure. The most significant independent predictors of time to graft failure were donor age, weight, and peak serum sodium; ischemia time; and recipient creatinine, international normalized ratio, and hepatitis C infection. The coefficients for each of these factors were compiled into a Transplant Risk Index formula. A cutoff of 5 resulted in a graft survival rate of 86% at 3 months, 76% at 1 year, and 62% at 3 years using Kaplan-Meier analysis. The predictive ability of the Transplant Risk Index was greater than the DRI or DMELD (the product of donor age and preoperative MELD) as assessed by the area under the receiver operating curve and the positive and negative predictive values. ConclusionThe Transplant Risk Index captures recipient factors and donor factors not captured in UNOS. Including these factors may improve the ability to predict good donor–recipient pairing.

Serum pancreastatin: The next predictive neuroendocrine tumor marker

Pancreastatin is a derived peptide of chromogranin A (CgA). Pancreastatin has the potential to be a diagnostic and predictive tumor marker in detecting NETs. Radioimmunoassay tests of pancreastatin and CgA were performed on 103 patient specimens collected at Mount Sinai Medical Center between 1/2010 and 7/2012. Patient demographics, diagnostic tests, surgical procedures, pathologic findings, adjuvant treatments, and survival were retrospectively reviewed. Statistical analysis utilized SPSS v20 software. Mean pancreastatin levels were significantly higher in the 92 NETs patients than in the 11 non-NETs patients (227.261 vs. 59.727, P < 0.05). Twenty-seven of the 92 patients with elevated pancreastatin levels (mean = 240.67), had normal CgA levels (mean = 4.65). Pancreastatin had sensitivity and specificity of 64% (59/92), and 100% (11/11). CgA had lower sensitivity and specificity of 43% (40/92), and 64% (7/11). In all 27 instances the pancreastatin concentration was found to be sole indicator of NET disease. When controlling for the level of CgA for the entire sample, a statistically significant difference was not found in the mean pancreastatin levels between both patient groups (P = 0.139, R = 0.484). Pancreastatin has greater sensitivity and specificity in diagnosing NETs than CgA. Further investigation of pancreastatin's diagnostic and predictive value is warranted.

Treatment outcomes and morbidity following definitive brachytherapy with or without external beam radiation for the treatment of localized prostate cancer: 20-Year experience at Mount Sinai Medical Center

ObjectivesTo present our treatment algorithm and 20-year experience in treating prostate cancer with brachytherapy since 1990, with focus on cancer-control outcomes and treatment-related morbidity. Methods and materialsWe selected patients treated for localized prostate cancer with brachytherapy, combination therapy with external beam radiotherapy, and adjuvant androgen deprivation therapy as prescribed by our Mount Sinai risk stratification and treatment algorithm. Outcomes were analyzed with respect to biochemical failure, distant metastases, prostate cancer-specific survival, and overall survival. Morbidity was assessed with respect to urinary, sexual, and rectal outcomes. ResultsIn total, 2,495 patients met inclusion criteria. The 12-year actuarial freedom from biochemical failure was 83% (low risk: 90%, intermediate risk: 84%, and high risk: 64%); freedom from distant metastasis was 95%; prostate cancer-specific survival was 95%; and overall survival was 70%. On multivariate analysis, significant associations were found between cancer control and risk group, total biologically effective dose, and androgen deprivation therapy. With regard to morbidity, potency was preserved in 61%, and urinary symptoms improved in 35%. The 12-year actuarial freedom from urinary retention events was 90% and from severe rectal bleed was 93%. ConclusionsBrachytherapy, as administered via the Mount Sinai algorithm, remains an efficacious and benign treatment option for patients with localized prostate cancer of all risk groups.

Low-Dose Right Unilateral Electroconvulsive Therapy (ECT)

Electroconvulsive therapy (ECT) is a widely used, highly effective antidepressant treatment. Except for the most severely ill patients, right unilateral (RUL) electrode placement is the most frequent initial treatment choice. In current practice, RUL ECT is administered at several multiples of seizure threshold (ST) based on reports that lower stimulus intensity results in lower response/remission rates. Many patients, as part of an initial dose titration to determine ST, will receive a single treatment with low-dose RUL ECT and subsequent treatments with a stimulus at a multiple of ST. To assess response to the first ECT. A retrospective analysis of charts from clinical practice at Mount Sinai Medical Center was performed. A single treatment with low-dose (presumably near ST) RUL ECT had a significant and immediate antidepressant effect in our sample of patients with major depression. We determined that this response is similar to that of patients receiving a single initial treatment with high-dose RUL ECT (at a multiple of ST). These data suggest, contrary to commonly held belief, that RUL ECT may be effective at a low stimulus dose. This argues against restimulating at 6 times ST in the initial session, based on the belief that the near-threshold seizure has no antidepressant efficacy. Our findings suggest a need for further investigation of cases in which low-dose RUL ECT may be an effective antidepressant treatment. Further prospective studies, including larger numbers of patients who receive randomized treatment with low- or high-dose RUL with longer follow-up, are indicated.

Interview: Interventional cardiology: a passion resulting in excellent outcomes

Samin K Sharma speaks to Caroline Telfer, Assistant Commissioning Editor Dr Samin K Sharma, MD, is the Professor of Medicine (Cardiology) at the Mount Sinai Medical Center (NY, USA), known for performing over 1600 complex coronary and valvular intervetions a year (the highest in the USA) with extremely low complication rates (<0.2%). He has had the highest success rate of angioplasty (New York State Department of Health Report) among interventional cardiologists in New York State from 1994–2003 and 2007–2008 receiving the prestigious double star status for statistically lower 30-day risk adjusted mortality. Samin Sharma has received many awards including ‘Best Teacher’, ‘Physician of the Year’ and the ‘Governor’s Excellence Award’. In 2012, he was named as a top doctor in US News and World Report.

Reply:

We very much appreciate the kind comments of Drs. Fuks, Durand, and Belghiti regarding our article.1 We agree that the microenvironment around the tumor provides valuable information regarding the potential for recurrence and death. However, we feel that this approach is still not ready for conventional clinical practice. Our 186-gene signature is able to define ∼20%-30% of resected patients who will be at high risk of late recurrence, hence de novo tumors, and death.1 Nonetheless, according to recent guidelines this biomarker needs further validation before being adopted into clinical practice or having a role in decision-making.2 Certainly, we endorse testing this signature in prospective studies to confirm its usefulness. Likewise, our current study finds that the presence of stage 4 fibrosis, or cirrhosis, in the surrounding liver correlates with recurrences more than 1 year after resection. These de novo cancers can potentially be considered for repeated hepatic resection, which can achieve excellent results in this setting rather than being referred for preemptive liver transplantation.3 Second, even in a setting where a gene profile obtained by biopsy from the adjacent tissue has been accepted by the scientific community, the main clinical utility will not be derived from deciding between resection or transplantation in patients with a poor prognostic signature, but rather in defining patients suitable for adjuvant therapies after resection. This is clearly an unmet medical need. Such therapies are not available at this point and whether interferon or even sorafenib (STORM) are going to show efficacy as adjuvant treatments remain unclear, and we are eager to know the results of ongoing trials.4 Thus, the results of our study support selecting patients with small hepatocellular carcinomas for resection as first choice and supports performing anatomic resection even in patients with stage 4 fibrosis. Once our gene-signature is mature enough for clinical practice, it may be considered in tailoring adjuvant therapies in a more personalized and cost-effective manner when such therapies are available. Sasan Roayaie M.D.*, Josep Llovet M.D.*, Myron Schwartz M.D.*, Vincenzo Mazzaferro M.D.*, * Department of Surgery, Mount Sinai Medical Center, New York, NY.

In Response

Department of Surgery Division of Colon and Rectal Surgery Mount Sinai Medical Center New York, NY The authors declare that they have nothing to disclose.