25 results on '"Jennifer R, DeFazio"'
Search Results
2. Esophageal Surveillance Practices in Esophageal Atresia Patients: A Survey by the Eastern Pediatric Surgery Network
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Malcolm N. Hamilton-Hall, Dana Jungbauer, Christine Finck, William Middlesworth, Benjamin Zendejas, Samuel M. Alaish, Cornelia L. Griggs, Robert T. Russell, Hester F. Shieh, Stefan Scholz, Shaun M. Kunisaki, Christina Feng, Melissa E. Danko, Jennifer R. DeFazio, Charles J. Smithers, Irving J. Zamora, and J. Leslie Knod
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Pediatrics, Perinatology and Child Health ,Surgery ,General Medicine - Published
- 2023
3. Outcomes and Resource Utilization Associated with Use of Routine Pre-Discharge White Blood Cell Count for Clinical Decision-Making in Children with Complicated Appendicitis: A Multicenter Hospital-Level Analysis
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Shannon L. Cramm, Dionne A. Graham, Martin L. Blakely, Nicole M. Chandler, Robert A. Cowles, Shaun M. Kunisaki, Robert T. Russell, Myron Allukian, Jennifer R. DeFazio, Cornelia L. Griggs, Matthew T. Santore, Stefan Scholz, Danielle I. Aronowitz, Brendan T. Campbell, Devon T. Collins, Sarah J. Commander, Abigail Engwall-Gill, Joseph R. Esparaz, Christina Feng, Claire Gerall, David N. Hanna, Olivia A. Keane, Abdulraouf Lamoshi, Aaron M. Lipskar, Claudia P. Orlas Bolanos, Elizabeth Pace, Maia D. Regan, Elisabeth T. Tracy, Sacha Williams, Lucy Zhang, and Shawn J. Rangel
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Pediatrics, Perinatology and Child Health ,Surgery ,General Medicine - Published
- 2023
4. Association of Gangrenous, Suppurative, and Exudative Findings With Outcomes and Resource Utilization in Children With Nonperforated Appendicitis
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Shannon L, Cramm, Aaron M, Lipskar, Dionne A, Graham, Shaun M, Kunisaki, Cornelia L, Griggs, Myron, Allukian, Robert T, Russell, Nicole M, Chandler, Matthew T, Santore, Danielle I, Aronowitz, Martin L, Blakely, Brendan, Campbell, Devon T, Collins, Sarah J, Commander, Robert A, Cowles, Jennifer R, DeFazio, Justice C, Echols, Joseph R, Esparaz, Christina, Feng, Richard A, Guyer, David N, Hanna, Katherine, He, Anastasia M, Kahan, Olivia A, Keane, Abdulraouf, Lamoshi, Carla M, Lopez, Sean E, McLean, Elizabeth, Pace, Maia D, Regan, Stefan, Scholz, Elisabeth T, Tracy, Sasha A, Williams, Lucy, Zhang, Shawn J, Rangel, and Goeto, Dantes
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Suppuration ,Appendix ,Length of Stay ,Infections ,Appendicitis ,Cohort Studies ,Gangrene ,Treatment Outcome ,Acute Disease ,Appendectomy ,Humans ,Surgical Wound Infection ,Surgery ,Child ,Original Investigation ,Retrospective Studies - Abstract
IMPORTANCE: The clinical significance of gangrenous, suppurative, or exudative (GSE) findings is poorly characterized in children with nonperforated appendicitis. OBJECTIVE: To evaluate whether GSE findings in children with nonperforated appendicitis are associated with increased risk of surgical site infections and resource utilization. DESIGN, SETTING, AND PARTICIPANTS: This multicenter cohort study used data from the Appendectomy Targeted Database of the American College of Surgeons Pediatric National Surgical Quality Improvement Program, which were augmented with operative report data obtained by supplemental medical record review. Data were obtained from 15 hospitals participating in the Eastern Pediatric Surgery Network (EPSN) research consortium. The study cohort comprised children (aged ≤18 years) with nonperforated appendicitis who underwent appendectomy from July 1, 2015, to June 30, 2020. EXPOSURES: The presence of GSE findings was established through standardized, keyword-based audits of operative reports by EPSN surgeons. Interrater agreement for the presence or absence of GSE findings was evaluated in a random sample of 900 operative reports. MAIN OUTCOMES AND MEASURES: The primary outcome was 30-day postoperative surgical site infections (incisional and organ space infections). Secondary outcomes included rates of hospital revisits, postoperative abdominal imaging, and postoperative length of stay. Multivariable mixed-effects regression was used to adjust measures of association for patient characteristics and clustering within hospitals. RESULTS: Among 6133 children with nonperforated appendicitis, 867 (14.1%) had GSE findings identified from operative report review (hospital range, 4.2%-30.2%; P
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- 2023
5. Association between Antibiotic Redosing Prior to Incision and Risk of Incisional Site Infection in Children with Appendicitis
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Shannon L. Cramm, Nicole M. Chandler, Dionne A. Graham, Shaun M. Kunisaki, Robert T. Russell, Martin L. Blakely, Aaron M. Lipskar, Myron Allukian, Danielle I. Aronowitz, Brendan T. Campbell, Devon T. Collins, Sarah J. Commander, Robert A. Cowles, Jennifer R. DeFazio, Joseph R. Esparaz, Christina Feng, Cornelia L. Griggs, Richard A. Guyer, David N. Hanna, Anastasia M. Kahan, Olivia A. Keane, Abdulraouf Lamoshi, Carla M. Lopez, Elizabeth Pace, Maia D. Regan, Matthew T. Santore, Stefan Scholz, Elisabeth T. Tracy, Sacha A. Williams, Lucy Zhang, and Shawn J. Rangel
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Surgery - Abstract
To evaluate whether redosing antibiotics within an hour of incision is associated with a reduction in incisional surgical site infection (iSSI) in children with appendicitis.Existing data remain conflicting as to whether children with appendicitis receiving antibiotics at diagnosis benefit from antibiotic redosing prior to incision.This was a multicenter retrospective cohort study using data from the Pediatric National Surgical Quality Improvement Program augmented with antibiotic utilization and operative report data obtained though supplemental chart review. Children undergoing appendectomy at 14 hospitals participating in the Eastern Pediatric Surgery Network from 7/2016-6/2020 who received antibiotics upon diagnosis of appendicitis between 1-6 hours prior to incision were included. Multivariable logistic regression was used to compare odds of iSSI in those who were and were not redosed with antibiotics within one hour of incision, adjusting for patient demographics, disease severity, antibiotic agents, and hospital-level clustering of events.3,533 children from 14 hospitals were included. Overall, 46.5% were redosed (hospital range: 1.8%-94.4%, P0.001) and iSSI rates were similar between groups (redosed: 1.2% vs. non-redosed: 1.3%; OR 0.84, [95%CI 0.39-1.83]). In subgroup analyses, redosing was associated with lower iSSI rates when cefoxitin was used as the initial antibiotic (redosed: 1.0% vs. non-redosed: 2.5%; OR 0.38, [95%CI 0.17-0.84]), but no benefit was found with other antibiotic regimens, longer periods between initial antibiotic administration and incision, or with increased disease severity.Redosing of antibiotics within one hour of incision in children who received their initial dose within 6 hours of incision was not associated with reduction in risk of incisional site infection unless cefoxitin was used as the initial antibiotic.
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- 2022
6. The use of fecal microbiota transplant in sepsis
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Robert Keskey, Jennifer Cone, John C. Alverdy, and Jennifer R. DeFazio
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0301 basic medicine ,Butyrate ,Article ,Immunophenotyping ,Sepsis ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,Physiology (medical) ,medicine ,Humans ,Innate immune system ,Mechanism (biology) ,business.industry ,Biochemistry (medical) ,Gastrointestinal Microbiome ,Public Health, Environmental and Occupational Health ,Brain ,General Medicine ,Fecal Microbiota Transplantation ,medicine.disease ,030104 developmental biology ,Butyrate-Producing Bacteria ,030220 oncology & carcinogenesis ,Immunology ,Animal studies ,business - Abstract
Sepsis is defined as a dysregulated inflammatory response, which ultimately results from a perturbed interaction of both an altered immune system and the biomass and virulence of involved pathogens. This response has been tied to the intestinal microbiota, as the microbiota and its associated metabolites play an essential role in regulating the host immune response to infection. In turn, critical illness as well as necessary health care treatments result in a collapse of the intestinal microbiota diversity and a subsequent loss of health-promoting short chain fatty acids, such as butyrate, leading to the development of a maladaptive pathobiome. These perturbations of the microbiota contribute to the dysregulated immune response and organ failure associated with sepsis. Several case series have reported the ability of fecal microbiota transplant (FMT) to restore the host immune response and aid in recovery of septic patients. Additionally, animal studies have revealed the mechanism of FMT rescue in sepsis is likely related to the ability of FMT to restore butyrate producing bacteria and alter the innate immune response aiding in pathogen clearance. However, several studies have reported lethal complications associated with FMT, including bacteremia. Therefore, FMT in the treatment of sepsis is and should remain investigational until a more detailed mechanism of how FMT restores the host immune response in sepsis is determined, allowing for the development of more fine-tuned microbiota therapies.
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- 2020
7. Neonates With Complex Cardiac Malformation and Congenital Diaphragmatic Hernia Born to SARS-CoV-2 Positive Women—A Single Center Experience
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Russell Miller, Emile A. Bacha, Lisa Saiman, Diana Vargas, Stéphanie Levasseur, Vincent Duron, Ganga Krishnamurthy, Jennifer R. DeFazio, Angelica Vasquez, Kinjal Desai, Alejandro Torres, David Kalfa, Nimrod Goldshtrom, Oliver M. Barry, Faith Kim, Damien J. LaPar, Dena Goffman, Svetlana Strletsova, William Middlesworth, Mariel E. Turner, and Palka R Gupta
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Heart Defects, Congenital ,Male ,2019-20 coronavirus outbreak ,Pediatrics ,medicine.medical_specialty ,Trisomy 13 Syndrome ,Coronavirus disease 2019 (COVID-19) ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,Complex cardiac malformation ,Single Center ,03 medical and health sciences ,0302 clinical medicine ,Pregnancy ,Prenatal Diagnosis ,Humans ,Medicine ,030212 general & internal medicine ,Pregnancy Complications, Infectious ,Pandemics ,030219 obstetrics & reproductive medicine ,SARS-CoV-2 ,business.industry ,Infant, Newborn ,Clinical course ,COVID-19 ,Congenital diaphragmatic hernia ,Original Articles ,General Medicine ,medicine.disease ,congenital heart disease ,Infectious Disease Transmission, Vertical ,Pediatrics, Perinatology and Child Health ,Female ,vertical transmission ,Surgery ,neonate ,Hernias, Diaphragmatic, Congenital ,Cardiology and Cardiovascular Medicine ,business - Abstract
Background: Our understanding of the impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on pregnancies and perinatal outcomes is limited. The clinical course of neonates born to women who acquired coronavirus disease 2019 (COVID-19) during their pregnancy has been previously described. However, the course of neonates born with complex congenital malformations during the COVID-19 pandemic is not known. Methods: We report a case series of seven neonates with congenital heart and lung malformations born to women who tested positive for SARS-CoV-2 during their pregnancy at a single academic medical center in New York City. Results: Six infants had congenital heart disease and one was diagnosed with congenital diaphragmatic hernia. In all seven infants, the clinical course was as expected for the congenital lesion. None of the seven exhibited symptoms generally associated with COVID-19. None of the infants in our case series tested positive by nasopharyngeal test for SARS-CoV-2 at 24 hours of life and at multiple points during their hospital course. Conclusions: In this case series, maternal infection with SARS-CoV-2 during pregnancy did not result in adverse outcomes in neonates with complex heart or lung malformations. Neither vertical nor horizontal transmission of SARS-CoV-2 was noted.
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- 2020
8. Multisystem Inflammatory Syndrome in Children Mimicking Surgical Pathologies: What Surgeons Need to Know about MIS-C
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Jennifer R. DeFazio, Claire D. Gerall, Sandra Kabagambe, Vincent Duron, Alexis B. Maddocks, and Cornelia L. Griggs
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medicine.medical_specialty ,2019-20 coronavirus outbreak ,Coronavirus disease 2019 (COVID-19) ,business.industry ,SARS-CoV-2 ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,MEDLINE ,COVID-19 ,Comorbidity ,Surgical procedures ,medicine.disease ,Appendicitis ,Magnetic Resonance Imaging ,Systemic Inflammatory Response Syndrome ,Need to know ,Surgical Procedures, Operative ,medicine ,Humans ,Surgery ,Female ,Intensive care medicine ,business ,Child - Published
- 2020
9. Delayed presentation and sub-optimal outcomes of pediatric patients with acute appendicitis during the COVID-19 pandemic
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Gabriel Apfel, Cornelia L. Griggs, Angela Kadenhe-Chiweshe, Claire D. Gerall, Weijia Fan, Anastasia M. Kahan, William Middlesworth, Vincent Duron, Daniel B. Fenster, Steven Stylianos, Jeffrey L. Zitsman, Nitsana Spigland, Jennifer R. DeFazio, Erica M. Fallon, and Sandra Kabagambe
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Pediatrics ,medicine.medical_specialty ,Multivariate analysis ,Perforation (oil well) ,Intra-abdominal abscess ,Article ,03 medical and health sciences ,0302 clinical medicine ,030225 pediatrics ,Severity of illness ,Medicine ,Appendectomy ,Humans ,Pediatrics, Perinatology, and Child Health ,Child ,Pandemics ,Retrospective Studies ,Appendiceal perforation ,Univariate analysis ,Acute appendicitis ,business.industry ,Proportional hazards model ,SARS-CoV-2 ,Hazard ratio ,COVID-19 ,General Medicine ,Length of Stay ,medicine.disease ,Appendicitis ,Exact test ,030220 oncology & carcinogenesis ,Pediatrics, Perinatology and Child Health ,New York City ,Surgery ,business - Abstract
Objective Early presentation and prompt diagnosis of acute appendicitis are necessary to prevent progression of disease leading to complicated appendicitis. We hypothesize that patients had a delayed presentation of acute appendicitis during the COVID-19 pandemic, which affected severity of disease on presentation and outcomes. Patients and methods We conducted a retrospective review of all patients who were treated for acute appendicitis at Morgan Stanley Children's Hospital (MSCH) between March 1, 2020 and May 31, 2020 when the COVID-19 pandemic was at its peak in New York City (NYC). For comparison, we reviewed patients treated from March 1, 2019 to May 31, 2019, prior to the pandemic. Demographics and baseline patient characteristics were analyzed for potential confounding variables. Outcomes were collected and grouped into those quantifying severity of illness on presentation to our ED, type of treatment, and associated post-treatment outcomes. Fisher's Exact Test and Kruskal-Wallis Test were used for univariate analysis while cox regression with calculation of hazard ratios was used for multivariate analysis. Results A total of 89 patients were included in this study, 41 patients were treated for appendicitis from March 1 to May 31 of 2019 (non-pandemic) and 48 were treated during the same time period in 2020 (pandemic). Duration of symptoms prior to presentation to the ED was significantly longer in patients treated in 2020, with a median of 2 days compared to 1 day (p = 0.003). Additionally, these patients were more likely to present with reported fever (52.1% vs 24.4%, p = 0.009) and had a higher heart rate on presentation with a median of 101 beats per minute (bpm) compared to 91 bpm (p = 0.040). Findings of complicated appendicitis on radiographic imaging including suspicion of perforation (41.7% vs 9.8%, p
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- 2020
10. Development of Pediatric Surgical Decision-Making Guidelines for COVID-19 in a New York City Children's Hospital☆
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William Middlesworth, Jennifer R. DeFazio, Erica M. Fallon, Sandra Kabagambe, Anastasia M. Kahan, Cornelia L. Griggs, Steven Stylianos, Vincent Duron, and Jeffrey L. Zitsman
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medicine.medical_specialty ,medicine.medical_treatment ,Decision Making ,Pneumonia, Viral ,Population ,Guidelines as Topic ,Article ,Betacoronavirus ,03 medical and health sciences ,0302 clinical medicine ,030225 pediatrics ,Health care ,Pediatric surgery ,Pandemic ,Extracorporeal membrane oxygenation ,Humans ,Medicine ,Pediatrics, Perinatology, and Child Health ,Child ,education ,Pandemics ,education.field_of_study ,SARS-CoV-2 ,business.industry ,COVID-19 ,General Medicine ,Evidence-based medicine ,Hospitals, Pediatric ,medicine.disease ,Coronavirus ,Oncology ,Surgical Procedures, Operative ,030220 oncology & carcinogenesis ,Pediatrics, Perinatology and Child Health ,Workforce ,New York City ,Surgery ,Laparoscopy ,Catchment area ,Medical emergency ,ECMO ,Coronavirus Infections ,business - Abstract
Objective During the COVID-19 pandemic, experience-based guidelines are needed in the pediatric population in order to deliver high quality care in a new way that keeps patients and healthcare workers safe and maximizes hospital resource utilization. Background The COVID-19 pandemic has created an unprecedented strain on national health care resources, particularly in New York City, the epicenter of the outbreak in the United States. Prudent allocation of surgical resources during the pandemic quickly became essential, and there is an unprecedented need to weigh the risks of operating versus delaying intervention in our pediatric patients. Methods Here we describe our experience in surgical decision-making during the COVID-19 pandemic in the pediatric surgical population at Morgan Stanley Children’s Hospital of New York-Presbyterian (MSCHONY), which has served as a major urban catchment area for COVID-19 positive pediatric patients. We describe how we have adjusted our current treatment of multiple facets of pediatric surgery including oncology, trauma, minimally invasive procedures, and extracorporeal membrane oxygenation (ECMO). Conclusions Our pediatric surgery department had to creatively and expeditiously adjust our protocols, guidelines, and workforce to not only serve our pediatric population but merge ourselves with our adult hospital system during the COVID pandemic. Type of Study Clinical Research Paper Level of Evidence Level V
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- 2020
11. Primary gastrojejunostomy tube placement using laparoscopy with endoscopic assistance: A novel technique
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Jennifer R. DeFazio, Sandra Kabagambe, Cornelia L. Griggs, Claire Gerall, Vincent Duron, and Ali-Andre Mencin
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Novel technique ,medicine.medical_specialty ,Gastric Bypass ,Risk profile ,03 medical and health sciences ,0302 clinical medicine ,Enteral Nutrition ,030225 pediatrics ,Gastrojejunostomy tube ,medicine ,Hollow viscus ,Fluoroscopy ,Humans ,Laparoscopy ,Child ,Intubation, Gastrointestinal ,Gastrostomy ,medicine.diagnostic_test ,business.industry ,General Medicine ,Endoscopy ,Surgery ,Gastrostomy tube ,030220 oncology & carcinogenesis ,Pediatrics, Perinatology and Child Health ,business - Abstract
Background Gastrojejunostomy (GJ) tubes are commonly used to provide postpyloric enteral nutrition in pediatric patients who cannot tolerate gastric feeds. Most techniques depend on a preexisting gastrostomy tube (GT) site to convert to a gastrojejunostomy. Several minimally invasive techniques have been described; however, their risk profile varies widely. Description of the operative technique We present a technique for primary laparoscopic GJ tube placement that minimizes the risk of hollow viscus injury and the use of fluoroscopy through endoscopic assistance. Results Eleven GJ tubes were placed using this technique in patients ranging from 5 months to 17 years of age and weighing 6.3 to 46.0 kg. Endoscopy through the gastrostomy site allowed direct visualization of wire and tube placement. There were no intraoperative or postoperative complications within 30 days of operation. Use of fluoroscopy was limited with minimal total radiation exposure. Conclusion The described technique of laparoscopic primary gastrojejunostomy tube placement with endoscopic assistance was associated with a low complication rate and minimal use of fluoroscopy. Level of evidence IV
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- 2020
12. Asymptomatic Congenital Lung Malformations: Timing of Resection Does Not Affect Adverse Surgical Outcomes
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Weijia Fan, Cornelia L. Griggs, Steven S. Rothenberg, Juliana Castrillon, Matthew P. Vivero, Vincent Duron, Emaad Iqbal, Jessica Price, Maggie J. Schmaedick, Ariela Zenilman, and Jennifer R. DeFazio
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medicine.medical_specialty ,medicine.medical_treatment ,Pediatrics ,Asymptomatic ,thoracoscopic surgery ,bronchopulmonary sequestration ,Intervention (counseling) ,Pediatric surgery ,pediatric surgery ,medicine ,congenital pulmonary adenomatous malformations ,Original Research ,surgical timing ,business.industry ,Incidence (epidemiology) ,lcsh:RJ1-570 ,lcsh:Pediatrics ,congenital lung and airway malformation ,medicine.disease ,Surgery ,Chest tube ,Exact test ,Pneumothorax ,lung resection surgery ,Pediatrics, Perinatology and Child Health ,Analysis of variance ,medicine.symptom ,business - Abstract
Background: Optimal timing for resection of asymptomatic congenital lung malformations (CLMs) remains controversial. The aim of this study is to define optimal timing for surgical intervention of patients with CLMs and define clinical variables that affect surgical outcomes. Methods: An IRB-approved retrospective analysis was conducted for patients undergoing surgery for CLMs between 2012 and 2017. Subjects were divided into cohorts based on timing of operative intervention. “Early intervention” was defined as surgery within 4 months of birth; “intermediate intervention”—between 4 and 6 months; and “late intervention”−6–12 months. Surgical outcomes including intraoperative estimated blood loss (EBL), surgical time, post-operative pneumothorax, length of time chest tube stayed in, and hospital length of stay were compared among the three groups using Fisher's exact test or Chi-squared test for categorical variables and one-way analysis of variance test for continuous variables. Results: We analyzed 63 patients who underwent surgery for CLM. There were no significant differences in baseline characteristics. Timing of surgery did not significantly correlate with post-operative outcomes. Specifically, there was no difference in operative time, EBL, post-operative pneumothorax, or length of hospital stay among the early, intermediate, and late intervention groups. Even after controlling for cyst-volume ratio (CVR), timing of surgery still did not affect post-operative outcomes. Conclusions: Surgical outcomes for resection of CLMs are not significantly affected by timing of surgery. We advocate for early intervention to decrease the incidence of associated complications that can occur with later intervention.
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- 2020
13. Surgical Interventions for Infant and Childhood Gastroesophageal Reflux Disease
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Claire Gerall and Jennifer R. DeFazio
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Pediatrics ,medicine.medical_specialty ,business.industry ,medicine.medical_treatment ,Reflux ,Disease ,medicine.disease ,digestive system diseases ,Review article ,Jejunostomy ,medicine ,GERD ,Early childhood ,business ,Surgical interventions ,Esophagitis - Abstract
Gastroesophageal reflux (GER) is a common condition in infants, thought to be the result of transient lower esophageal sphincter relaxations which occur independent of swallowing. Most cases of GER are physiologic and generally resolve by early childhood. Gastroesophageal reflux disease (GERD) is diagnosed when symptoms persist or complications such as aspiration or esophagitis develop. Currently there is wide practice variation in the surgical treatment of severe infant and childhood reflux with multiple acceptable surgical approaches chosen based on individual disease characteristics as well as surgeon preference. In this review article we discuss the use of laparoscopic fundoplication, gastrojejunostomy and jejunostomy tube placement to mitigate the symptoms of GERD. Although these minimally invasive techniques have greatly advanced treatment in infants and children, a paucity of data exists comparing outcomes of each technique, resulting in a lack of consensus on best technique. Surgical approach to GERD treatment is an important area of research that needs further investigation.
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- 2020
14. Modeling Acinetobacter baumannii wound infections
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Luis A. Actis, Alexander Zaborin, Irma D. Fleming, Jennifer R. DeFazio, Olga Zaborina, Laxmipradha Chandrasekar, John C. Alverdy, Natalia Belogortseva, and Monika A. Krezalek
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Acinetobacter baumannii ,0301 basic medicine ,Siderophore ,Virulence Factors ,Iron ,Blotting, Western ,030106 microbiology ,Rectus Abdominis ,Ischemia ,Virulence ,Abdominal Injuries ,Moths ,Critical Care and Intensive Care Medicine ,Article ,Microbiology ,Mice ,03 medical and health sciences ,medicine ,Animals ,biology ,Inoculation ,business.industry ,Wild type ,biochemical phenomena, metabolism, and nutrition ,medicine.disease ,biology.organism_classification ,Mice, Inbred C57BL ,Galleria mellonella ,Disease Models, Animal ,030104 developmental biology ,Wound Infection ,Crush injury ,Surgery ,business ,Acinetobacter Infections - Abstract
BACKGROUND Acinetobacter baumannii has emerged as an increasingly important and successful opportunistic human pathogen due to its ability to withstand harsh environmental conditions, its characteristic virulence factors, and quick adaptability to stress. METHODS We developed a clinically relevant murine model of A. baumannii traumatic wound infection to determine the effect of local wound environment on A. baumannii virulence. Mice underwent rectus muscle crush injury combined with ischemia created by epigastric vessel ligation, followed by A. baumannii inoculation. Reiterative experiments were performed using (1) a mutant deficient in the production of the siderophore acinetobactin, or (2) iron supplementation of the wound milieu. Mice were euthanized 7 days later, and rectus muscle analyzed for signs of clinical infection, HIF1α accumulation, bacterial abundance, and colony morphotype. To determine the effect of wound milieu on bacterial virulence, Galleria mellonella infection model was used. RESULTS The combination of rectus muscle injury with ischemia and A. baumannii inoculation resulted in 100% incidence of clinical wound infection that was significantly higher compared with other groups (n = 15/group, p < 0.0001). The highest level of wound infection was accompanied by the highest level of A. baumannii colonization (p < 0.0001) and the highest degree of HIF1α accumulation (p < 0.05). A. baumannii strains isolated from injured/ischemic muscle with clinical infection displayed a rough morphotype and a higher degree of virulence as judged by G. mellonella killing assay as compared with smooth morphotype colonies isolated from injured muscle without clinical infection (100% vs. 60%, n = 30 Log-Rank test, p = 0.0422). Iron supplementation prevented wound infection (n = 30, p < 0.0001) and decreased HIF1α (p = 0.039643). Similar results of decrease in wound infection and HIF1α were obtained when A. baumannii wild type was replaced with its derivative mutant [INCREMENT]BasD deficient in acinetobactin production. CONCLUSION The ability of A. baumannii to cause infections in traumatized wound relies on its ability to scavenge iron and can be prevented by iron supplementation to the wound milieu.
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- 2017
15. Critical role of microbiota within cecal crypts on the regenerative capacity of the intestinal epithelium following surgical stress
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Namrata Setia, Olga Zaborina, Qiti Guo, Natalia Belogortseva, Vytautas P. Bindokas, Monika A. Krezalek, John C. Alverdy, Jennifer R. DeFazio, Sanjiv Hyoju, and Alexander Zaborin
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0301 basic medicine ,Male ,Surgical stress ,Physiology ,Biology ,digestive system ,Receptors, G-Protein-Coupled ,03 medical and health sciences ,Cecum ,Lgr5 ,Mice ,0302 clinical medicine ,fluids and secretions ,Intestinal mucosa ,Physiology (medical) ,epithelial regeneration ,medicine ,Animals ,Homeostasis ,proliferative zone ,Intestinal Mucosa ,surgical stress ,Hepatology ,Microbiota ,digestive, oral, and skin physiology ,Gastroenterology ,LGR5 ,apoptosis ,fecal microbial transplant ,Surgical Injury ,Intestinal epithelium ,digestive system diseases ,Mice, Inbred C57BL ,030104 developmental biology ,medicine.anatomical_structure ,Gene Expression Regulation ,030220 oncology & carcinogenesis ,Immunology ,cecal crypt microbiota ,Research Article - Abstract
This study provides novel insight into the process by which surgical injury places the intestinal epithelium at risk for colonization by pathogenic microbes and impairment of its regenerative capacity via loss of its microbiota. We show that fecal transplant restores crypt homeostasis in association with repopulation of the microbiota within cecal crypts., Cecal crypts represent a unique niche that are normally occupied by the commensal microbiota. Due to their density and close proximity to stem cells, microbiota within cecal crypts may modulate epithelial regeneration. Here we demonstrate that surgical stress, a process that invariably involves a short period of starvation, antibiotic exposure, and tissue injury, results in cecal crypt evacuation of their microbiota. Crypts devoid of their microbiota display pathophysiological features characterized by abnormal stem cell activation as judged by leucine-rich repeat-containing G protein-coupled receptor 5 (Lgr5) staining, expansion of the proliferative zone toward the tips of the crypts, and an increase in apoptosis. In addition, crypts devoid of their microbiota display loss of their regenerative capacity as assessed by their ability to form organoids ex vivo. When a four-member human pathogen community isolated from the stool of a critically ill patient is introduced into the cecum of mice with empty crypts, crypts become occupied by the pathogens and further disruption of crypt homeostasis is observed. Fecal microbiota transplantation restores the cecal crypts’ microbiota, normalizes homeostasis within crypts, and reestablishes crypt regenerative capacity. Taken together, these findings define an emerging role for the microbiota within cecal crypts to maintain epithelial cell homeostasis in a manner that may enhance recovery in response to the physiological stress imposed by the process of surgery. NEW & NOTEWORTHY This study provides novel insight into the process by which surgical injury places the intestinal epithelium at risk for colonization by pathogenic microbes and impairment of its regenerative capacity via loss of its microbiota. We show that fecal transplant restores crypt homeostasis in association with repopulation of the microbiota within cecal crypts.
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- 2016
16. Splenic rupture in an extremely low birthweight infant
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Vincent Duron, Jennifer Hammond, Aaron Wallman-Stokes, and Jennifer R. DeFazio
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medicine.medical_specialty ,Abdominal compartment syndrome ,Hyperkalemia ,Exploratory laparotomy ,medicine.medical_treatment ,Day of life ,lcsh:Surgery ,Exchange transfusion ,03 medical and health sciences ,0302 clinical medicine ,030225 pediatrics ,medicine ,business.industry ,lcsh:RJ1-570 ,lcsh:Pediatrics ,lcsh:RD1-811 ,medicine.disease ,Surgery ,030220 oncology & carcinogenesis ,Pediatrics, Perinatology and Child Health ,Gestation ,Pulmonary hemorrhage ,medicine.symptom ,business ,Premature rupture of membranes - Abstract
Splenic rupture is a rare event in preterm and term infants. Symptoms of splenic rupture include acute blood loss, abdominal distention, and hypotension. We present the case of a 24 4/7 weeks gestation male infant born in the setting of preterm premature rupture of membranes who developed splenic rupture at 24 hours of life. Initially, the infant was managed medically. As the symptoms of abdominal compartment syndrome worsened, a bedside exploratory laparotomy was performed. The infant died on day of life 16 after developing hyperkalemia and pulmonary hemorrhage during an exchange transfusion for profound hyperbilirubinemia. This is the first report describing the management of splenic rupture in an extremely premature infant.
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- 2020
17. Morphine Promotes Colonization of Anastomotic Tissues with Collagenase - Producing Enterococcus faecalis and Causes Leak
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Joseph F. Petrosino, Jennifer R. DeFazio, Nadim J. Ajami, Daniel P. Smith, Luke A. Versten, John C. Alverdy, Monika A. Krezalek, Irma D. Fleming, Scott Christley, Olga Zaborina, Robin Klabbers, James N. Luo, Alexander Zaborin, Kristina Guyton, Baddr A. Shakhsheer, and Natalia Belogortseva
- Subjects
Male ,0301 basic medicine ,medicine.drug_class ,Exploratory laparotomy ,medicine.medical_treatment ,Antibiotics ,Analgesic ,Anastomotic Leak ,Anastomosis ,Article ,Enterococcus faecalis ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Animals ,Collagenases ,Rats, Wistar ,Digestive System Surgical Procedures ,Wound Healing ,Morphine ,biology ,business.industry ,Gastroenterology ,biology.organism_classification ,In vitro ,Analgesics, Opioid ,030104 developmental biology ,030220 oncology & carcinogenesis ,Anesthesia ,Collagenase ,Surgery ,business ,medicine.drug - Abstract
BACKGROUND: Despite ever more powerful antibiotics, newer surgical techniques, and enhanced recovery programs, anastomotic leaks remain a clear and present danger to patients. Previous work from our laboratory suggests that anastomotic leakage may be caused by Enterococcus faecalis strains that express a high collagenase phenotype (i.e., collagenolytic). Yet the mechanisms by which the practice of surgery shifts or selects for collagenolytic phenotypes to colonize anastomotic tissues remain unknown. METHODS: Here, we hypothesized that morphine, an analgesic agent universally used in gastrointestinal surgery, promotes tissue colonization with collagenolytic E. faecalis and causes anastomotic leak. To test this, rats were administered morphine in a chronic release form as would occur during routine surgery or vehicle. Rats were observed for 6 days and then underwent exploratory laparotomy for anastomotic inspection and tissue harvest for microbial analysis. These results provide further rationale to enhanced recovery after surgery (i.e., ERAS) programs that suggest limiting or avoiding the use of opioids in gastrointestinal surgery. RESULTS: Results demonstrated that compared to placebo-treated rats, morphine-treated rats demonstrated markedly impaired anastomotic healing and gross leaks that correlated with the presence of high collagenase-producing E. faecalis adherent to anastomotic tissues. To determine the direct role of morphine on this response, various isolates of E. faecalis from the rats were exposed to morphine and their collagenase activity and adherence capacity determined in vitro. Morphine increased both the adhesiveness and collagenase production of four strains of E. faecalis harvested from anastomotic tissues, two that were low collagenase producers at baseline, and two that were high collagenase producers at baseline. CONCLUSION: These results provide further rationale to enhanced recovery after surgery (i.e., ERAS) programs that suggest limiting or avoiding the use of opioids in gastrointestinal surgery.
- Published
- 2016
18. Retained gastrostomy bumper resulting in esophageal fistula and spinal osteomyelitis
- Author
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Jennifer R. DeFazio, Erica M. Fallon, William Middlesworth, Cornelia L. Griggs, Joseph A Picoraro, and Ariela Zenilman
- Subjects
medicine.medical_specialty ,Radiographic imaging ,medicine.medical_treatment ,lcsh:Surgery ,Fistulous tract ,03 medical and health sciences ,Esophagus ,0302 clinical medicine ,medicine ,Esophageal Fistula ,business.industry ,Osteomyelitis ,lcsh:RJ1-570 ,Soft tissue ,lcsh:Pediatrics ,lcsh:RD1-811 ,List: gastrostomy ,medicine.disease ,Gastrostomy ,Surgery ,Foreign body ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Pediatrics, Perinatology and Child Health ,Esophageal fistula ,030211 gastroenterology & hepatology ,business ,Torticollis - Abstract
Background We report a case of spinal osteomyelitis and fistulous tract between the esophagus and prevertebral soft tissues secondary to an esophageal foreign body. This resulted from a retained gastrostomy bumper that broke on removal of the tube seven years earlier. Case presentation A 9-year-old male with Troyer Syndrome and developmental delay presented to his pediatrician with the refusal to bear weight and new onset torticollis, and was referred to our institution for further evaluation. He was admitted for further workup due to concern for a neurological process. Imaging revealed osteomyelitis of T3/T4 and inflammatory changes in the posterior mediastinum with possible communication with the esophagus. His gastrostomy tube (GT) was converted to a gastrojejunal tube (GJT) for post-pyloric feeding. He acutely worsened after this procedure, and further radiographic imaging revealed a retained foreign body in the esophagus. An upper endoscopy was subsequently performed with snare removal of the object, identified as the bumper of a previous gastrostomy tube. This esophageal foreign body caused esophageal erosion leading to creation of a fistulous tract with nidus for infection spread posteriorly. The patient underwent prolonged treatment for the infection, with improvement in his presenting symptoms, and eventually resumed gastrostomy feeding. Conclusion Retained foreign body following gastrostomy removal, while typically does not warrant further investigation, may present with significant sequelae if retained especially in children with developmental delay and feeding difficulties.
- Published
- 2020
19. Bacterial colonization and succession in a newly opened hospital
- Author
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Irma Flemming, Emily Landon, Naseer Sangwan, Peter E. Larsen, Daniel P. Smith, Kim M. Handley, Miles Richardson, John C. Alverdy, Simon Lax, Rob Knight, Baddr A. Shakhsheer, Kristina Guyton, Brent Stephens, Jeffrey A. Siegel, Benjamin D. Shogan, Monika A. Krezalek, Jennifer R. DeFazio, Sylvia Garcia-Houchins, Stephen G. Weber, and Jack A. Gilbert
- Subjects
0301 basic medicine ,medicine.medical_specialty ,Isolation (health care) ,business.industry ,medicine.drug_class ,Transmission (medicine) ,030106 microbiology ,Antibiotics ,General Medicine ,Ecological succession ,medicine.disease_cause ,03 medical and health sciences ,030104 developmental biology ,Bacterial colonization ,Antibiotic resistance ,Metagenomics ,Internal medicine ,Medicine ,business ,Intensive care medicine ,Staphylococcus - Abstract
The microorganisms that inhabit hospitals may influence patient recovery and outcome, although the complexity and diversity of these bacterial communities can confound our ability to focus on potential pathogens in isolation. To develop a community-level understanding of how microorganisms colonize and move through the hospital environment, we characterized the bacterial dynamics among hospital surfaces, patients, and staff over the course of 1 year as a new hospital became operational. The bacteria in patient rooms, particularly on bedrails, consistently resembled the skin microbiota of the patient occupying the room. Bacterial communities on patients and room surfaces became increasingly similar over the course of a patient's stay. Temporal correlations in community structure demonstrated that patients initially acquired room-associated taxa that predated their stay but that their own microbial signatures began to influence the room community structure over time. The α- and β-diversity of patient skin samples were only weakly or nonsignificantly associated with clinical factors such as chemotherapy, antibiotic usage, and surgical recovery, and no factor except for ambulatory status affected microbial similarity between the microbiotas of a patient and their room. Metagenomic analyses revealed that genes conferring antimicrobial resistance were consistently more abundant on room surfaces than on the skin of the patients inhabiting those rooms. In addition, persistent unique genotypes of Staphylococcus and Propionibacterium were identified. Dynamic Bayesian network analysis suggested that hospital staff were more likely to be a source of bacteria on the skin of patients than the reverse but that there were no universal patterns of transmission across patient rooms.
- Published
- 2017
20. Phosphate-Containing Polyethylene Glycol Polymers Prevent Lethal Sepsis by Multidrug-Resistant Pathogens
- Author
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David J. Goldfeld, David G. Camp, Joel H. Collier, Jennifer R. DeFazio, John C. Alverdy, Alexandria Alverdy, Joshua N. Adkins, Bana Jabri, Matthew J. Kade, Olga Zaborina, Alexander Zaborin, Matthew Tirrell, Sangman M. Kim, Brooke L. Deatherage Kaiser, Millicent A. Firestone, Richard D. Smith, and Natalia Belogortseva
- Subjects
Acinetobacter baumannii ,Virulence ,Biology ,medicine.disease_cause ,Phosphates ,Polyethylene Glycols ,Microbiology ,Mice ,Antibiotic resistance ,Intestinal mucosa ,Drug Resistance, Multiple, Bacterial ,Sepsis ,Candida albicans ,Enterococcus faecalis ,medicine ,Animals ,Humans ,Pharmacology (medical) ,Microbiome ,Intestinal Mucosa ,Mechanisms of Action: Physiological Effects ,Pharmacology ,Pseudomonas aeruginosa ,Candidiasis ,Bacterial Infections ,Cytostatic Agents ,biology.organism_classification ,Survival Analysis ,Mice, Inbred C57BL ,Multiple drug resistance ,Infectious Diseases ,Bacteria - Abstract
Antibiotic resistance among highly pathogenic strains of bacteria and fungi is a growing concern in the face of the ability to sustain life during critical illness with advancing medical interventions. The longer patients remain critically ill, the more likely they are to become colonized by multidrug-resistant (MDR) pathogens. The human gastrointestinal tract is the primary site of colonization of many MDR pathogens and is a major source of life-threatening infections due to these microorganisms. Eradication measures to sterilize the gut are difficult if not impossible and carry the risk of further antibiotic resistance. Here, we present a strategy to contain rather than eliminate MDR pathogens by using an agent that interferes with the ability of colonizing pathogens to express virulence in response to host-derived and local environmental factors. The antivirulence agent is a phosphorylated triblock high-molecular-weight polymer (here termed Pi-PEG 15–20) that exploits the known properties of phosphate (P i ) and polyethylene glycol 15-20 (PEG 15-20) to suppress microbial virulence and protect the integrity of the intestinal epithelium. The compound is nonmicrobiocidal and appears to be highly effective when tested both in vitro and in vivo . Structure functional analyses suggest that the hydrophobic bis-aromatic moiety at the polymer center is of particular importance to the biological function of Pi-PEG 15-20, beyond its phosphate content. Animal studies demonstrate that Pi-PEG prevents mortality in mice inoculated with multiple highly virulent pathogenic organisms from hospitalized patients in association with preservation of the core microbiome.
- Published
- 2014
21. Proceedings of the 2014 A.S.P.E.N. Research Workshop
- Author
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Michael J. Morowitz, Daniel H. Teitelbaum, Michael J. Sadowsky, Jack A. Gilbert, Jennifer R. DeFazio, Eugene B. Chang, and John C. Alverdy
- Subjects
Nutrition and Dietetics ,Interface (Java) ,media_common.quotation_subject ,Human microbiome ,Medicine (miscellaneous) ,Biology ,Bioinformatics ,Nutrition science ,Data science ,Gut microbiome ,Human health ,Cyberinfrastructure ,Microbiome ,Function (engineering) ,media_common - Abstract
The human and earth microbiomes are among the most important biological agents in understanding and preventing disease. Technology is advancing at a fast pace and allowing for high-resolution analysis of the composition and function of our microbial partners across regions, space, and time. Bioinformaticists and biostatisticians are developing ever more elegant displays to understand the generated megadatasets. A virtual cyberinfrastructure of search engines to cross-reference the rapidly developing data is emerging in line with technologic advances. Nutrition science will reap the benefits of this new field, and its role in preserving the earth and the humans who inhabit it will become evidently clear. In this report we highlight some of the topics of an A.S.P.E.N.-sponsored symposium held during Clinical Nutrition Week in 2013 that address the importance of the human microbiome to human health and disease.
- Published
- 2013
22. The shift of an intestinal 'microbiome' to a 'pathobiome' governs the course and outcome of sepsis following surgical injury
- Author
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Alexander Zaborin, Olga Zaborina, John C. Alverdy, Jennifer R. DeFazio, and Monika A. Krezalek
- Subjects
0301 basic medicine ,medicine.medical_specialty ,Resuscitation ,Critical Care and Intensive Care Medicine ,Article ,Sepsis ,03 medical and health sciences ,0302 clinical medicine ,Postoperative Complications ,Intensive care ,Antibiotic therapy ,Medicine ,Humans ,Elective surgery ,Intensive care medicine ,Intraoperative Complications ,business.industry ,Microbiota ,030208 emergency & critical care medicine ,medicine.disease ,Surgical Injury ,Prolonged exposure ,Gastrointestinal Tract ,Intensive Care Units ,030104 developmental biology ,Intestinal Microbiome ,Emergency Medicine ,business - Abstract
Sepsis following surgical injury remains a growing and worrisome problem following both emergent and elective surgery. Although early resuscitation efforts and prompt antibiotic therapy have improved outcomes in the first 24 to 48 h, late onset sepsis is now the most common cause of death in modern intensive care units. This time shift may be, in part, a result of prolonged exposure of the host to the stressors of critical illness which, over time, erode the health promoting intestinal microbiota and allow for virulent pathogens to predominate. Colonizing pathogens can then subvert the immune system and contribute to the deterioration of the host response. Here, we posit that novel approaches integrating the molecular, ecological, and evolutionary dynamics of the evolving gut microbiome/pathobiome during critical illness are needed to understand and prevent the late onset sepsis that develops following prolonged critical illness.
- Published
- 2016
23. Toxic Epidermal Necrolysis with Gastrointestinal Involvement: A Case Report and Review of the Literature
- Author
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Jennifer R. DeFazio, Craig S. Brown, John Hart, Gary An, Emma Whitcomb, Annemarie O'Connor, and Lawrence J. Gottlieb
- Subjects
medicine.medical_specialty ,Gout ,Gastrointestinal Diseases ,Allopurinol ,Rectum ,Gout Suppressants ,030207 dermatology & venereal diseases ,03 medical and health sciences ,0302 clinical medicine ,Medicine ,Humans ,Esophagus ,Aged ,Gastrointestinal tract ,business.industry ,Rehabilitation ,Clinical course ,Sigmoid colon ,medicine.disease ,Dermatology ,Intestinal epithelium ,Toxic epidermal necrolysis ,medicine.anatomical_structure ,Stevens-Johnson Syndrome ,Emergency Medicine ,030211 gastroenterology & hepatology ,Surgery ,Female ,Complication ,business - Abstract
Gastrointestinal involvement is a rare complication of toxic epidermal necrolysis syndrome (TENS) that results in sloughing of the intestinal epithelium. Prior case reports have noted the potential susceptibility of the entire gastrointestinal tract, from oropharynx and esophagus to sigmoid colon and rectum. Given its infrequency, the effect of gastrointestinal involvement on the treatment and prognosis of TENS is poorly understood. Here, the authors report a case of gastrointestinal symptoms in a patient diagnosed with toxic epidermal necrolysis, likely representing gastrointestinal involvement. In addition, the authors describe the histopathologic and endoscopic characteristics of the involved mucosa, clinical course, and present a review of the literature of this rare but potentially impactful complication of TENS.
- Published
- 2016
24. The opposing forces of the intestinal Microbiome and the emerging pathobiome
- Author
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Olga Zaborina, Jennifer R. DeFazio, Baddr A. Shakhsheer, John C. Alverdy, and Irma D. Fleming
- Subjects
Proteomics ,Pathology ,medicine.medical_specialty ,Anastomotic Leak ,Disease ,Article ,Postoperative Complications ,Sepsis ,Drug Resistance, Bacterial ,Preoperative Care ,Medicine ,Humans ,Surgical Wound Infection ,Microbiome ,business.industry ,Cathartics ,Microbiota ,Human microbiome ,Antibiotic Prophylaxis ,Intestines ,Intestinal Microbiome ,Surgery ,Engineering ethics ,Metagenomics ,business ,Surgical patients - Abstract
This article summarizes emerging concepts on the role of the intestinal microbiome in surgical patients. Revolutionary research over the past decade has shown that human beings live in close and constant contact with boundless communities of microbes. Recent innovations in the study of the human microbiome are reviewed. To demonstrate the applicability of these studies to surgical disease, the authors discuss what is known about the role of microbes in the pathogenesis of perioperative complications. Enhanced awareness of the human microbiome will empower clinicians to adopt novel practices in the prevention and treatment of a variety of surgical conditions.
- Published
- 2014
25. Intestinal Application of Pi-PEG Maintains the Health-promoting Microbiota, Suppresses the Effect of Gut Pathobiota on Immune Signaling, and Prevents Mortality in Mice
- Author
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D. Camp, Jennifer R. DeFazio, Irma D. Fleming, Olga Zaborina, Alexander Zaborin, Sinil Kim, Bana Jabri, B. Kaiser, and John C. Alverdy
- Subjects
Immune signaling ,PEG ratio ,Pi ,Surgery ,Biology ,Cell biology - Published
- 2014
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