Steven D Freedman

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

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Publications (111)863.56 Total impact

  • [Show abstract] [Hide abstract]
    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. · 3.01 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; · 3.74 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.
    Healthcare. 07/2014;
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    ABSTRACT: 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 A4 would prevent lung injury in a murine model of BPD.
    PLoS ONE 06/2014; 9(6):e98773. · 3.53 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; · 2.18 Impact Factor
  • Gastroenterology 05/2014; 146(5):S-4. · 12.82 Impact Factor
  • Bharath D Nath, Steven D Freedman, A James Moser
    JAMA surgery. 09/2013; 148(11).
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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%.Am J Gastroenterol advance online publication, 28 May 2013; doi:10.1038/ajg.2013.148.
    The American Journal of Gastroenterology 05/2013; · 9.21 Impact Factor
  • Gastroenterology 11/2012; · 12.82 Impact Factor
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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. · 3.65 Impact Factor
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    ABSTRACT: There is limited literature on acute pancreatitis (AP), acute recurrent pancreatitis (ARP), and chronic pancreatitis (CP) in children. The International Study Group of Pediatric Pancreatitis: In Search for a Cure (INSPPIRE) consortium was formed to standardize definitions, develop diagnostic algorithms, investigate disease pathophysiology, and design prospective multicenter studies in pediatric pancreatitis. Subcommittees were formed to delineate definitions of pancreatitis, and a survey was conducted to analyze present practice. AP was defined as requiring 2 of the following: abdominal pain compatible with AP, serum amylase and/or lipase values ≥3 times upper limits of normal, and imaging findings of AP. ARP was defined as ≥2 distinct episodes of AP with intervening return to baseline. CP was diagnosed in the presence of typical abdominal pain plus characteristic imaging findings, or exocrine insufficiency plus imaging findings, or endocrine insufficiency plus imaging findings. We found that children with pancreatitis were primarily managed by pediatric gastroenterologists. Unless the etiology was known, initial investigations included serum liver enzymes, triglycerides, calcium, and abdominal ultrasound. Further investigations (usually for ARP and CP) included magnetic resonance or other imaging, sweat chloride, and genetic testing. Respondents' future goals for INSPPIRE included determining natural history of pancreatitis, developing algorithms to evaluate and manage pancreatitis, and validating diagnostic criteria. INSPPIRE represents the first initiative to create a multicenter approach to systematically characterize pancreatitis in children. Future aims include creation of patient database and biologic sample repository.
    Journal of pediatric gastroenterology and nutrition 02/2012; 55(3):261-5. · 2.18 Impact Factor
  • Steven D Freedman, Camilia R Martin
    The virtual mentor : VM. 01/2012; 14(7):560-2.
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    ABSTRACT: QUALITY PROBLEM: Patients often do not fully understand medical information discussed during office visits. This can result in lack of adherence to recommended treatment plans and poorer health outcomes. We conducted a prospective quality improvement intervention at a large tertiary-care academic medical center utilizing the encounter form and studied the effect on patient satisfaction, understanding and confidence in communicating with physicians. The intervention included 108 patients seen by seven physicians in five sub-specialties. Ninety-eight percent of patients were extremely satisfied (77%) or somewhat satisfied (21%) with the program. Ninety-six percent of patients reported being involved in decisions about their care and treatments as well as high levels of understanding of medical information that was discussed during visit. Sixty-nine percent of patients reported that they shared the encounter form with their families and friends. Patients' self-confidence in communicating with their doctors increased from a score of 8.1 to 8.7 post-intervention (P-value = 0.0018). When comparing pre- and post-intervention experiences, only 38% of patients felt that their problems and questions were adequately addressed by other physicians' pre-intervention, compared with 94% post-intervention. We introduced a program to enhance physician-patient communication and found that patients were highly satisfied, more informed and more actively involved in their care. This approach may be an easily generalizable approach to improving physician-patient communication at outpatient visits.
    International Journal for Quality in Health Care 12/2011; 24(4):357-64. · 1.79 Impact Factor
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    ABSTRACT: Primary sclerosing cholangitis (PSC) is characterised by progressive inflammatory and fibrotic destruction of the biliary ducts. There are no effective medical therapies and presently high dose ursodeoxycholic acid is no longer recommended due to significant adverse events in a recent clinical trial. Cystic fibrosis transmembrane conductance regulator (CFTR) dysfunction is associated with PSC in both children and adults. Since CFTR dysfunction leads to altered fatty acid metabolism, specifically reduced docosahexaenoic acid (DHA), we hypothesised that DHA supplementation might be an effective therapy for patients with PSC. To determine the safety and efficacy of oral DHA supplementation for the treatment of PSC. We conducted a 12 month open-label pilot study to evaluate safety of oral DHA and its effects on serum alkaline phosphatase as a primary outcome measure in 23 patients with PSC. DHA was administered orally at 800 mg twice per day. Secondary outcomes included changes in other liver function tests and fibrosis biomarkers. A 1.7-fold increase in serum DHA levels was observed with supplementation. The mean alkaline phosphatase level (±S.E.) at baseline was 357.8 ± 37.1 IU compared to 297.1 ± 23.7 IU (P < 0.05) after 12 months of treatment. There were no changes in other liver function tests and fibrosis biomarkers. No adverse events were reported. Oral DHA supplementation is associated with an increase in serum DHA levels and a significant decline in alkaline phosphatase levels in patients with PSC. These data support the need for a rigorous trial of DHA therapy in PSC.
    Alimentary Pharmacology & Therapeutics 11/2011; 35(2):255-65. · 4.55 Impact Factor
  • Journal of cystic fibrosis: official journal of the European Cystic Fibrosis Society 08/2011; 11(1):72-3; author reply 74-75. · 3.19 Impact Factor
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    ABSTRACT: To measure the changes in whole blood fatty acid levels in premature infants and evaluate associations between these changes and neonatal morbidities. This was a retrospective cohort study of 88 infants born at <30 weeks' gestation. Serial fatty acid profiles during the first postnatal month and infant outcomes, including chronic lung disease (CLD), retinopathy of prematurity, and late-onset sepsis, were analyzed. Regression modeling was applied to determine the association between fatty acid levels and neonatal morbidities. Docosahexaenoic acid (DHA) and arachidonic acid levels declined rapidly in the first postnatal week, with a concomitant increase in linoleic acid levels. Decreased DHA level was associated with an increased risk of CLD (OR, 2.5; 95% CI, 1.3-5.0). Decreased arachidonic acid level was associated with an increased risk of late-onset sepsis (hazard ratio, 1.4; 95% CI, 1.1-1.7). The balance of fatty acids was also a predictor of CLD and late-onset sepsis. An increased linoleic acid:DHA ratio was associated with an increased risk of CLD (OR, 8.6; 95% CI, 1.4-53.1) and late-onset sepsis (hazard ratio, 4.6; 95% CI, 1.5-14.1). Altered postnatal fatty acid levels in premature infants are associated with an increased risk of CLD and late-onset sepsis.
    The Journal of pediatrics 06/2011; 159(5):743-749.e1-2. · 4.02 Impact Factor
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    ABSTRACT: Chronic visceral pain is frequent, extremely debilitating, and generally resistant to pharmacological treatment. It has been shown that chronic visceral inflammation, through altered afferent visceral sensory input, leads to plastic changes in the central nervous system that ultimately sustain pain. Therefore approaches aiming at modulation of brain activity are attractive candidates to control visceral pain. Here we report findings of a phase II, sham-controlled clinical trial assessing the clinical effects and brain metabolic correlates of a 10-day course of daily sessions of slow-frequency, repetitive transcranial magnetic stimulation (rTMS) targeting the right secondary somatosensory cortex (SII) in patients with chronic pancreatitis and severe visceral pain. Our results show a significant reduction in pain after real rTMS that lasted for at least 3 weeks following treatment. These clinical changes were correlated with increases in glutamate and N-acetyl aspartate (NAA) levels--neurometabolites associated with cortical activity and brain damage--as measured by in vivo single-voxel proton magnetic resonance spectroscopy (1H-MRS). Adverse effects in the real rTMS group were mild and short-lasting. Our results support preliminary findings showing that modulation of right SII with rTMS is associated with a significant analgesic effect and that this effect is correlated with an increase in excitatory neurotransmitter levels such as glutamate and NAA.
    European journal of pain (London, England) 01/2011; 15(1):53-60. · 3.37 Impact Factor
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    ABSTRACT: Hemolysis of serum or plasma can exclude very valuable samples from longitudinal studies, particular over time course, and risks the loss of valuable data. In human sera, the concentration of albumin is nearly ten billion times greater than that of cell-signaling proteins like the interleukins. The relative proportions of such rare, but extremely important biomarkers is further decreased in hemolyzed samples in which hemogloblin may nearly double the total protein concentration. Further, hemogloblin removal alone does not significantly decrease sample complexity. Sample prefractionation ideally partitions high abundance proteins like albumin, IgG, and hemoglobin into fractions separate from those containing the protein(s) of interest, potentially enabling enrichment and increasing the sensitivity of downstream microassays attempting to quantify these critical molecules. Samples from a neonatal depository are hoped to provide valuable information on pro-inflammatory response during the first days of life. However, such samples are extremely rare and frequently hemolyzed. To derive meaningful data from hemolyzed whole bloods and sera, fractionation schemes based of protein molecular mass, charge, or affinity were investigated as means of hemoglobin depletion with concomitant biomarker enrichment. Size separations were performed by sequential ultrafiltration with decreasing molecular weight cutoffs (MWCOs) to produce distinct size fractions, or by electrophoresis in the GELFREE System. Charge fractions were evaluated in the OFFGEL Fractionator or a Digital Protein Chip (dPC) capable of producing fractions of 0.05 pI unit intervals as well as pH specific column binding and elution. For affinity based separations, The ProteoMiner immobilized hexapeptide ligand library was used to isolate low abundance proteins without requiring prior hemoglobin depletion.
    2010 AIChE Annual Meeting; 11/2010
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    ABSTRACT: Cystic fibrosis (CF) patients display a fatty acid imbalance characterized by low linoleic acid levels and variable changes in arachidonic acid. This led to the recommendation that CF patients consume a high-fat diet containing >6% linoleic acid. We hypothesized that increased conversion of linoleic acid to arachidonic acid in CF leads to increased levels of arachidonate-derived proinflammatory metabolites and that this process is exacerbated by increasing linoleic acid levels in the diet. To test this hypothesis, we determined the effect of linoleic acid supplementation on downstream proinflammatory biomarkers in two CF models: 1) in vitro cell culture model using 16HBE14o(-) sense [wild-type (WT)] and antisense (CF) human airway epithelial cells; and 2) in an in vivo model using cftr(-/-) transgenic mice. Fatty acids were analyzed by gas chromatography-mass spectrometry (GC/MS), and IL-8 and eicosanoids were measured by ELISA. Neutrophils were quantified in bronchoalveolar lavage fluid from knockout mice following linoleic acid supplementation and exposure to aerosolized Pseudomonas LPS. Linoleic acid supplementation increased arachidonic acid levels in CF but not WT cells. IL-8, PGE(2), and PGF(2α) secretion were increased in CF compared with WT cells, with a further increase following linoleic acid supplementation. cftr(-/-) Mice supplemented with 100 mg of linoleic acid had increased arachidonic acid levels in lung tissue associated with increased neutrophil infiltration into the airway compared with control mice. These findings support the hypothesis that increasing linoleic acid levels in the setting of loss of cystic fibrosis transmembrane conductance regulator (CFTR) function leads to increased arachidonic acid levels and proinflammatory mediators.
    AJP Lung Cellular and Molecular Physiology 11/2010; 299(5):L599-606. · 3.52 Impact Factor
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    ABSTRACT: A new approach in the treatment of cystic fibrosis involves improving the function of mutant cystic fibrosis transmembrane conductance regulator (CFTR). VX-770, a CFTR potentiator, has been shown to increase the activity of wild-type and defective cell-surface CFTR in vitro. We randomly assigned 39 adults with cystic fibrosis and at least one G551D-CFTR allele to receive oral VX-770 every 12 hours at a dose of 25, 75, or 150 mg or placebo for 14 days (in part 1 of the study) or VX-770 every 12 hours at a dose of 150 or 250 mg or placebo for 28 days (in part 2 of the study). At day 28, in the group of subjects who received 150 mg of VX-770, the median change in the nasal potential difference (in response to the administration of a chloride-free isoproterenol solution) from baseline was -3.5 mV (range, -8.3 to 0.5; P=0.02 for the within-subject comparison, P=0.13 vs. placebo), and the median change in the level of sweat chloride was -59.5 mmol per liter (range, -66.0 to -19.0; P=0.008 within-subject, P=0.02 vs. placebo). The median change from baseline in the percent of predicted forced expiratory volume in 1 second was 8.7% (range, 2.3 to 31.3; P=0.008 for the within-subject comparison, P=0.56 vs. placebo). None of the subjects withdrew from the study. Six severe adverse events occurred in two subjects (diffuse macular rash in one subject and five incidents of elevated blood and urine glucose levels in one subject with diabetes). All severe adverse events resolved without the discontinuation of VX-770. This study to evaluate the safety and adverse-event profile of VX-770 showed that VX-770 was associated with within-subject improvements in CFTR and lung function. These findings provide support for further studies of pharmacologic potentiation of CFTR as a means to treat cystic fibrosis. (Funded by Vertex Pharmaceuticals and others; number, NCT00457821.).
    New England Journal of Medicine 11/2010; 363(21):1991-2003. · 54.42 Impact Factor

Publication Stats

4k Citations
863.56 Total Impact Points


  • 1995–2014
    • Beth Israel Deaconess Medical Center
      • • Division of Gastroenterology
      • • Department of Neonatology
      • • Pancreas Center
      • • Department of Medicine
      • • Department of Obstetrics and Gynecology
      • • Department of Surgery
      Boston, Massachusetts, United States
  • 1993–2014
    • Harvard Medical School
      Boston, Massachusetts, United States
  • 2011
    • University of California, San Francisco
      • Division of Hospital Medicine
      San Francisco, CA, United States
    • Sydney Children's Hospital
      Sydney, New South Wales, Australia
  • 2010
    • SickKids
      Toronto, Ontario, Canada
  • 2009
    • Universidade Presbiteriana Mackenzie
      • Centro de Ciências Biológicas e da Saúde (CCBS)
      São Paulo, Estado de Sao Paulo, Brazil
  • 2007
    • Massachusetts General Hospital
      • Department of Pathology
      Boston, MA, United States
    • University of Toronto
      • Hospital for Sick Children
      Toronto, Ontario, Canada
  • 2006–2007
    • Boston Children's Hospital
      Boston, Massachusetts, United States
  • 2005
    • University of Cincinnati
      • Division of Digestive Diseases
      Cincinnati, OH, United States
  • 1991
    • Dana-Farber Cancer Institute
      Boston, Massachusetts, United States