Steven D Freedman

Beth Israel Deaconess Medical Center, Boston, Massachusetts, United States

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Publications (126)995.79 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: To quantify absorption coefficients of specific fatty acids in preterm infants as a function of diet, formula (F) or breast milk (BM), and postnatal age; and, to identify the fatty acid structural characteristics that determine optimal fatty acid absorption. Fatty acids from dietary and fecal samples were extracted and quantified by gas chromatography-mass spectroscopy. Fatty acid absorption coefficients (FA-CFAs) were calculated by comparing the total amount of fatty acids supplied by the diet to the amount quantified in the total fecal output over a 3-day period. 18 infants (BM = 8; F = 10) were studied at 2 weeks of age and 20 infants (BM = 10; F = 10) were studied at 6 weeks of age. FA-CFAs decreased with increasing carbon length in formula-fed infants at 2 and 6 weeks. Results were similar, but less in magnitude in breast milk-fed infants at 2 weeks with no difference at 6 weeks. Preterm infants fed formula demonstrated lower FA-CFAs as a function of increasing carbon length. This is consistent with limited pancreatic lipase production and with lipase being present in breast milk but not in formula. The fact that this pattern was seen in BM-fed infants at 2 weeks but not 6 weeks of age suggests that intestinal immaturity may also play a role in impaired fatty acid absorption. These data highlight principles that need to be considered to optimize delivery and absorption of dietary LCPUFAs in preterm infants.
    Journal of pediatric gastroenterology and nutrition 08/2015; DOI:10.1097/MPG.0000000000000934 · 2.63 Impact Factor
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    ABSTRACT: Surgical intervention is uncommon in chronic pancreatitis. Literature largely describes single institution or international experiences. This study describes US-based chronic pancreatitis surgical management. Retrospective analysis of chronic pancreatitis patients in the Healthcare Cost and Utilization Project Florida State Inpatient Database 2007-2011. Patients with malignancy or congenital abnormalities were excluded. Univariate analysis using the chi-square test. The number of readmissions, inpatient length of stay and cost using Wilcoxon's signed-rank test. Multivariate analysis of surgery by logistic regression. Twenty-one thousand four hundred and forty-five patients with chronic pancreatitis. 10.8% (2 307) underwent surgery including 1652 cholecystectomies, 564 drainage procedures and 498 pancreatectomies. Procedures decreased from 12.1% to 8.3% over time (P < 0.001), but intervention within 3 months increased (7.2% to 8.4%; P = 0.017). 15.3% (3 278) had pancreatic cysts/pseudocysts and 43.4% (9 312) had diabetes. The median numbers of admissions were 2 [interquartile range (IQR) 1,5] and 3 (IQR 2,7) among non-surgical and surgical patients, respectively (P < 0.001). Predictors of surgery were fewer co-morbidities, private insurance, and either diabetes mellitus or pancreatic cyst/pseudocyst. Chronic pancreatitis leads to numerous inpatient readmissions, but surgical intervention only occurs in a minority of cases. Complicated patients are more likely to undergo surgery. The complexities of chronic pancreatitis management warrant early multidisciplinary evaluation and ongoing consideration of surgical and non-surgical options. © 2015 International Hepato-Pancreato-Biliary Association.
    HPB 07/2015; 17(9). DOI:10.1111/hpb.12459 · 2.68 Impact Factor
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    ABSTRACT: Morbidities of impaired immunity and dysregulated inflammation are common in preterm infants. Postnatal Intestinal development plays a critical role in the maturation of the immune system and is, in part, driven by exposure to an enteral diet. The aim of this study was to evaluate the influence of the timing of the first enteral feeding on intestinal inflammation and risk of disease. 130 infants <33 weeks' gestation were studied. Maternal and infant data were abstracted from the medical record. Single and multiplex ELISA assays quantified cytokines from fecal and serum samples at two weeks postnatal age. A delay in enteral feedings after the third postnatal day is associated with a 4.5 (95% CI 1.8-11.5, p=0.002) fold increase in chronic lung disease, 2.9 (1.1-7.8, p=0.03) fold increase in retinopathy of prematurity, and 3.4 (1.2-9.8, p=0.02) fold increase in multiple comorbidities compared to infants fed on or before the third day. Additionally, a delay in the initiation of feedings is associated with increased fecal IL-8 levels and a decreased IL-10:IL-8 ratio. A delay in enteral feeding is associated with intestinal inflammation and increased risks of morbidities. To improve neonatal outcomes, early nutritional practices need to be reevaluated.
    PLoS ONE 07/2015; 10(7):e0132924. DOI:10.1371/journal.pone.0132924 · 3.23 Impact Factor
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    ABSTRACT: Chronic obstructive pulmonary disease (COPD) is an inflammatory process characterized by airway mucus hypersecretion. Lipopolysaccharides (LPS) are known to stimulate the production of mucin 5AC (MUC5AC) via epidermal growth factor receptor (EGFR) in human airway cells. Noteworthy, we have previously demonstrated that EGFR/Rac1/reactive oxygen species (ROS)/matrix metalloproteinase 9 (MMP-9) is a key signaling cascade regulating MUC5AC production in airway cells challenged with LPS. Various reports have shown an inverse association between the intake of polyunsaturated fatty acids (PUFA) of the n-3 (omega-3) family or fish consumption and COPD. In the present study, we investigated the influence of docosahexaenoic acid (DHA), one of the most important omega-3 PUFA contained in fish oil, on the production of MUC5AC in LPS-challenged human airway cells NCI-H292. Our results indicate that DHA is capable of counteracting MUC5AC overproduction in LPS-stimulated cells by abrogating both EGFR phosphorylation and its downstream signaling pathway. This signaling pathway not only includes Rac1, ROS and MMP-9, but also NF-κB, since we have found that ROS require NF-κB activity to induce MMP-9 secretion and activation. Copyright © 2015. Published by Elsevier Inc.
    Biochemical and Biophysical Research Communications 06/2015; 463(4). DOI:10.1016/j.bbrc.2015.06.056 · 2.30 Impact Factor
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    ABSTRACT: To examine if surgery performed for pain of chronic pancreatitis (CP) within 3 years diagnosis has greater odds of achieving complete pain relief than later surgery and to find optimal surgical timing for attaining pain relief in CP. Retrospective review of records at a tertiary institution 2003 to 2011 for CP where the operative indication was pain. Outcomes were pain-free status, opioid use, and pancreatic insufficiency at 3-year follow-up. Univariate analysis by Fisher exact tests. Receiver operating curve to calculate cutoff threshold time for surgery. Outcomes for 66 patients were included. Median preoperative CP duration was 28 months (interquartile range, 12, 67). Twenty-six patients (39.4%) were free of pain at the 3-year follow-up. Thirty-four patients (51.5%) were opioid users at follow-up. Postoperatively, 34 patients (51.5%) demonstrated endocrine, and 32 patients (48.5%) demonstrated exocrine insufficiency. The optimal cutoff point for preoperative CP duration was 26.5 months (area under the curve, 0.66). Shorter duration of CP before surgery was a predictor of pain-free status and reduced postoperative opioid use at follow-up. Results from a single institution analysis suggest early surgical intervention of 26.5 months or less of diagnosis is associated with improved pain control, and optimal timing for surgery may be earlier than previously thought.
    Pancreas 04/2015; 44(5). DOI:10.1097/MPA.0000000000000333 · 2.96 Impact Factor
  • Gastroenterology 04/2015; 148(4):S-909. DOI:10.1016/S0016-5085(15)33084-5 · 16.72 Impact Factor
  • Gyanprakash A Ketwaroo · Steven D Freedman · Sunil G Sheth
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    ABSTRACT: Chronic pancreatitis (CP) represents a significant health care burden in the United States. Diagnosing it early and accurately is important for the efficient management of these patients. However, the early diagnosis of CP, when structural and functional pancreatic changes are subtle, remains difficult. Complicating this is the large cohort of patients with nonspecific abdominal pain who are often suspected of having early CP and who utilize significant health care resources in attempts at diagnosis and management. We present a review of the current diagnostic tests available for making an early diagnosis of CP. We further report our approach to patients suspected of having CP based on the available literature.
    Pancreas 03/2015; 44(2):173-180. DOI:10.1097/MPA.0000000000000239 · 2.96 Impact Factor
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    ABSTRACT: To determine the clinical presentation, diagnostic variables, risk factors, and disease burden in children with chronic pancreatitis. We performed a cross-sectional study of data from the International Study Group of Pediatric Pancreatitis: In Search for a Cure, a registry of children with acute recurrent pancreatitis and chronic pancreatitis. Between-group differences were compared using Wilcoxon rank-sum test. Among 170 subjects in the registry, 76 (45%) had chronic pancreatitis; 57% were female, 80% were white; median age at diagnosis was 9.9 years. Pancreatitis-predisposing genetic mutations were identified in 51 (67%) and obstructive risk factors in 25 (33%). Toxic/metabolic and autoimmune factors were uncommon. Imaging demonstrated ductal abnormalities and pancreatic atrophy more commonly than calcifications. Fifty-nine (77%) reported abdominal pain within the past year; pain was reported as constant and receiving narcotics in 28%. Children with chronic pancreatitis reported a median of 3 emergency department visits and 2 hospitalizations in the last year. Forty-seven subjects (70%) missed 1 day of school in the past month as the result of chronic pancreatitis; 26 (34%) missed 3 or more days. Children reporting constant pain were more likely to miss school (P = .002), visit the emergency department (P = .01), and experience hospitalizations (P = .03) compared with children with episodic pain. Thirty-three children (43%) underwent therapeutic endoscopic retrograde pancreatography; one or more pancreatic surgeries were performed in 30 (39%). Chronic pancreatitis occurs at a young age with distinct clinical features. Genetic and obstructive risk factors are common, and disease burden is substantial. Copyright © 2015 Elsevier Inc. All rights reserved.
    Journal of Pediatrics 12/2014; 166(4). DOI:10.1016/j.jpeds.2014.11.019 · 3.79 Impact Factor
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    Steven D. Freedman · Camilia R. Martin · Mara G. Aspinall
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    ABSTRACT: The patient׳s experiences and costs related to their care are largely dictated by each patient-physician interaction along the continuum of care. However, the amount of time that a physician spends with a patient creating a medical action plan is highly variable and often not related to the severity or complexity of the patient׳s condition. Adding a structured process to guide and inform patient-physician encounters, including outlining expectations and follow-up by both sides is needed. Addressing these barriers to the physician-patient relationship would reduce variation in care, minimize unnecessary trial and error tactics and instead focus on predicted cost effective actions. Copyright © 2014 Elsevier Inc. All rights reserved.
    Healthcare 07/2014; 2(2). DOI:10.1016/j.hjdsi.2014.02.002
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    ABSTRACT: Background: Surgical intervention has traditionally been reserved as the last management option for pain in chronic pancreatitis. Recently, there has been a call for surgery to be offered earlier in the disease process. The objectives of this review were to evaluate the effect of early surgery on postoperative pain, pancreatic function, and re-intervention rates in chronic pancreatitis. Methods: A systematic literature search through EMBASE, Cochrane Review, and PubMed from January 1950 to January 2014 was conducted. Citations found in relevant papers are hand-searched. Data which could be pooled were analyzed using Revman (v5.2). Risk of bias analysis was conducted. Results: Of the 2,886 potentially eligible studies identified, 11 studies met the inclusion criteria. There was large heterogeneity in the study designs, and studies were conducted over a lengthy time span. Seven studies examined pain, three studies examined pancreatic function, and three studies examined rates of re-intervention. Meta-analysis of the three studies with comparative raw data regarding complete pain relief showed that early surgery was associated with an increased likelihood of complete postoperative pain relief (RR = 1.67, 95% CI 1.09-2.56, p = 0.02). Early surgery was also associated with reduced risk of pancreatic insufficiency and low re-intervention rates. Conclusions: Data from this study supports considering early surgery for pain management in patients with chronic pancreatitis, with the potential of a reduced risk of pancreatic insufficiency and the need for further intervention. Further prospective randomized studies are warranted comparing early surgery against conservative step-up approaches.
    Journal of Gastrointestinal Surgery 06/2014; 18(10). DOI:10.1007/s11605-014-2571-8 · 2.80 Impact Factor
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    ABSTRACT: Background: The critical fatty acids Docosahexaenoic Acid (DHA) and Arachidonic Acid (AA) decline in preterm infants within the first postnatal week and are associated with neonatal morbidities, including bronchopulmonary dysplasia (BPD). DHA and AA are precursors to downstream metabolites that terminate the inflammatory response. We hypothesized that treatment with Resolvin D1 and/or Lipoxin A(4) would prevent lung injury in a murine model of BPD. Objective: To determine the effect of Resolvin D1 and/or Lipoxin A(4) on hyperoxia-induced lung injury. Methods: C57/BL6 pups were randomized at birth to Room Air, Hyperoxia (>90% oxygen), Hyperoxia + Resolvin D1, Hyperoxia + Lipoxin A(4), or Hyperoxia + Resolvin D1/Lipoxin A(4). Resolvin D1 and/or Lipoxin A(4) (2 ng/g) were given IP on days 0, 3, 6, and 9. On day 10, mice were sacrificed and lungs collected for morphometric analyses including Mean Linear Intercept (MLI), Radial Alveolar Count (RAC), and Septal Thickness (ST); RT-PCR analyses of biomarkers of lung development and inflammation; and ELISA for TGF beta(1) and TGF beta(2). Result: The increased ST observed with hyperoxia exposure was normalized by both Resolvin D1 and Lipoxin A(4); while, hyperoxia-induced alveolar simplification was attenuated by Lipoxin A(4). Relative to hyperoxia, Resolvin D1 reduced the gene expression of CXCL2 (2.9 fold), TIMP1 (6.7 fold), and PPAR gamma (4.8 fold). Treatment with Lipoxin A(4) also led to a reduction of CXCL2 (2.4 fold) while selectively increasing TGF beta(2) (2.1 fold) and Smad3 (1.58 fold). Conclusion: The histologic and biochemical changes seen in hyperoxia-induced lung injury in this murine model can be reversed by the addition of DHA and AA fatty acid downstream metabolites that terminate the inflammatory pathways and modulate growth factors. These fatty acids or their metabolites may be novel therapies to prevent or treat lung injury in preterm infants.
    PLoS ONE 06/2014; 9(6):e98773. DOI:10.1371/journal.pone.0098773 · 3.23 Impact Factor
  • Pancreatology 06/2014; 14(3):S40. DOI:10.1016/j.pan.2014.05.513 · 2.84 Impact Factor
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    ABSTRACT: Acute recurrent pancreatitis (ARP) and chronic pancreatitis (CP) are rare and poorly understood diseases in children. Better understanding of these disorders can only be accomplished via a multi-center, structured, data collection approach. The INSPPIRE Consortium (INternational Study Group of Pediatric Pancreatitis: In search for a cuRE) was created to investigate the epidemiology, etiologies, pathogenesis, natural history and outcomes of pediatric ARP and CP. Patient and physician questionnaires were developed to capture information on demographics, past medical history, family and social history, medications, hospitalizations, risk factors, diagnostic evaluation, treatments and outcome information. Information collected in paper questionnaires was then transferred into REDCap (Research Electronic Data Capture), tabulated and analyzed. The administrative structure of the INSPPIRE Consortium was established and National Institutes of Health funding was obtained. Fourteen sites (10 in United States, 2 in Canada, and 2 overseas) participated. Questionnaires were amended and updated as necessary, followed by changes made into the REDCap database. Between September 1, 2012 and August 31, 2013, 194 children were enrolled into the study; 54% were female; 82% were non-Hispanic, 72% were Caucasian. The INSPPIRE consortium demonstrates the feasibility of building a multi-center patient registry to study the rare pediatric diseases, ARP and CP. Analyses of collected data will provide a greater understanding of pediatric pancreatitis and create opportunities for therapeutic interventional studies that would not otherwise be possible without a multi-center approach.
    Journal of pediatric gastroenterology and nutrition 05/2014; DOI:10.1097/MPG.0000000000000417 · 2.63 Impact Factor
  • Gastroenterology 05/2014; 146(5):S-4. DOI:10.1016/S0016-5085(14)60011-1 · 16.72 Impact Factor
  • Pediatric Pulmonology 10/2013; 48:416-416. · 2.70 Impact Factor
  • Steven Freedman · Camilia R. Martin
    Pediatric Pulmonology 10/2013; 48:125-126. · 2.70 Impact Factor
  • Bharath D Nath · Steven D Freedman · A James Moser
    JAMA SURGERY 09/2013; 148(11). DOI:10.1001/jamasurg.2013.3753 · 3.94 Impact Factor
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    ABSTRACT: Objectives: The diagnosis of chronic pancreatitis in patients with characteristic symptoms but normal pancreatic imaging is challenging. Assessment of pancreatic function through secretin pancreatic function testing (SPFT) has been advocated in this setting, but its diagnostic accuracy is not fully known. Methods: This was a retrospective review of patients who received SPFT at our tertiary care institution between January 1995 and December 2008 for suspected chronic pancreatitis. For all patients, medical records were reviewed for evidence of subsequent development of chronic pancreatitis by imaging and/or pathology. Patients were then categorized as "true positive" or "true negative" for chronic pancreatitis based on follow-up imaging or histologic evidence. Results: In all, 116 patients underwent SPFT. Of the 27 patients who tested positive, 7 were lost to follow-up. Of the remaining 20 SPFT-positive patients, 9 (45%) developed radiologic or histologic evidence of chronic pancreatitis after a median of 4 years (1-11 years). Of the 89 patients who had negative SPFT testing, 19 were lost to follow-up. Of the remaining 70 patients, 2 were eventually diagnosed with chronic pancreatitis based on subsequent imaging/histology after a median follow-up period of 7 years (3-11 years). The sensitivity of the SPFT in diagnosing chronic pancreatitis was 82% with a specificity of 86%. The positive predictive value (PPV) of chronic pancreatitis was 45% with a negative predictive value (NPV) of 97%. Conclusions: In patients with suspected early chronic pancreatitis and normal pancreatic imaging, SPFT is highly accurate at ruling out early chronic pancreatitis with a NPV of 97%.
    The American Journal of Gastroenterology 05/2013; 108(8). DOI:10.1038/ajg.2013.148 · 10.76 Impact Factor
  • Pediatric Academic Societies Annual Meeting; 01/2013
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    ABSTRACT: Cystic fibrosis liver disease (CFLD) is a rapidly progressive biliary fibrosis, resembling primary sclerosing cholangitis that develops in 5-10% of patients with cystic fibrosis. Further research and evaluation of therapies are hampered by the lack of a mouse model for CFLD. Although primary sclerosing cholangitis is linked to both ulcerative colitis and loss of cystic fibrosis transmembrane conductance regulator (CFTR) ion channel function, induction of colitis with dextran sodium sulfate (DSS) in cftr(-/-) mice causes bile duct injury but no fibrosis. Since profibrogenic modifier genes are linked to CFLD, we examined whether subthreshhold doses of the profibrogenic xenobiotic 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC), along with DSS-induced colitis, lead to bile duct injury and liver fibrosis in mice that harbor loss of CFTR function. Exon 10 heterozygous (cftr(+/-)) and homozygous (cftr(-/-)) mice treated with DDC demonstrated extensive mononuclear cell inflammation, bile duct proliferation, and periductular fibrosis. In contrast, wild-type (cftr(+/+)) littermates did not develop bile duct injury or fibrosis. Histological changes corresponded to increased levels of alkaline phosphatase, hydroxyproline, and expression of profibrogenic transcripts for transforming growth factor-β(1), transforming growth factor-β(2), procollagen α(1)(I), and tissue inhibitor of matrix metaloproteinase-1. Immunohistochemistry demonstrated fibrosis and activation of periductal fibrogenic cells based on positive staining for lysyl oxidase-like-2, α-smooth muscle actin, and collagen I. These data demonstrate that subthreshold doses of DDC, in conjunction with DSS-induced colitis, results in bile duct injury and periductal fibrosis in mice with partial or complete loss of CFTR function and may represent a useful model to study the pathogenic mechanisms by which CFTR dysfunction predisposes to fibrotic liver disease and potential therapies.
    AJP Gastrointestinal and Liver Physiology 06/2012; 303(4):G474-81. DOI:10.1152/ajpgi.00055.2012 · 3.80 Impact Factor

Publication Stats

5k Citations
995.79 Total Impact Points

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  • 1998–2015
    • Beth Israel Deaconess Medical Center
      • • Division of Translational Research
      • • Division of Gastroenterology
      • • Pancreas Center
      • • Department of Medicine
      • • Department of Obstetrics and Gynecology
      Boston, Massachusetts, United States
    • Massachusetts General Hospital
      • Division of Gastroenterology
      Boston, Massachusetts, United States
  • 1991–2014
    • Harvard Medical School
      • Department of Medicine
      Boston, Massachusetts, United States
  • 1994–2013
    • Harvard University
      Cambridge, Massachusetts, United States
    • Beth Israel Medical Center
      New York, New York, United States
  • 2007–2009
    • Universidade Presbiteriana Mackenzie
      • Centro de Ciências Biológicas e da Saúde (CCBS)
      São Paulo, Estado de Sao Paulo, Brazil
    • Boston Children's Hospital
      Boston, Massachusetts, United States
    • University of Toronto
      • Department of Paediatrics
      Toronto, Ontario, Canada
  • 1996–2001
    • Philipps University of Marburg
      • Institut für Zytobiologie und Zytopathologie
      Marburg, Hesse, Germany
  • 2000
    • Beverly Hospital, Boston MA
      BVY, Massachusetts, United States