Publications by authors named "Michael J Rosen"

203 Publications

IL-33 is produced by colon fibroblasts and differentially regulated in acute and chronic murine colitis.

Sci Rep 2021 May 5;11(1):9575. Epub 2021 May 5.

Division of Gastroenterology, Hepatology and Nutrition, Cincinnati Children's Hospital Medical Center, 3333 Burnet Ave, MLC 2010, Cincinnati, OH, 45229, USA.

IL-33 is upregulated in ulcerative colitis and has a protective role in chemically-induced acute murine colitis. We aimed to determine whether IL-33 influences Il10 chronic colitis and its cellular source in health and during colitis. Il10Il33 and Il10Il33 littermates developed colitis of similar severity. Colon Il33 was induced in WT and Il10 mice exposed to DSS, but not in unchallenged Il10 mice with colitis. Il33-citrine reporter mice showed that Il33-citrine colocalized with α-smooth muscle actin myofibroblasts and vimentin fibroblasts in WT mice. CitrineCD74CD90 inflammatory fibroblasts were increased with DSS treatment. IL-1β induced Il33 expression in colon myofibroblasts, but colon Il33 expression did not differ between DSS-treated WT and Il1r1 mice. In conclusion, deficiency of IL-33 does not alter the severity of chronic colitis in Il10 mice. Induction of Il33 upon DSS exposure in WT and Il10 mice, but not in unchallenged Il10 mice, suggests epithelial injury induces colon IL-33. Fibroblasts are the primary colonic source of IL-33 and IL-33-expressing CD90CD74 fibroblasts are increased during DSS-induced colitis. IL-1β induces Il33 in colon myofibroblasts in vitro, but signaling through the IL-1R1 is not necessary for induction of IL-33 in DSS-induced colitis.
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http://dx.doi.org/10.1038/s41598-021-89119-1DOI Listing
May 2021

Does PROVE-IT Really Prove Anything of Value?-Reply.

JAMA Surg 2021 Apr 28. Epub 2021 Apr 28.

Cleveland Clinic Center for Abdominal Core Health, Digestive Diseases and Surgery Institute, The Cleveland Clinic Foundation, Cleveland Clinic, Cleveland, Ohio.

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http://dx.doi.org/10.1001/jamasurg.2021.0957DOI Listing
April 2021

Can Hernia Sac to Abdominal Cavity Volume Ratio Predict Fascial Closure Rate for Large Ventral Hernia? Reliability of the Tanaka Score.

J Am Coll Surg 2021 Apr 5. Epub 2021 Apr 5.

Center for Abdominal Core Health, Digestive Disease and Surgery Institute, Cleveland Clinic Foundation, Cleveland, OH.

Background: The hernia sac to abdominal cavity volume ratio (VR) on abdominal CT was described previously as a way to predict which hernias would be less likely to achieve fascial closure. The aim of this study was to test the reliability of the previously described cutoff ratio in predicting fascial closure in a cohort of patients with large ventral hernias.

Methods: Patients who underwent elective, open incisional hernia repair of 18 cm or larger width at a single center were identified. The primary end point of interest was fascial closure for all patients. Secondary outcomes included operative details and abdominal wall-specific quality-of-life metrics. We used VR as a comparison variable and calculated the test characteristics (ie, sensitivity, specificity, and positive and negative predictive values).

Results: A total of 438 patients were included, of which 337 (77%) had complete fascial closure and 101 (23%) had incomplete fascial closure. The VR cutoff of 25% had a sensitivity of 76% (95% CI, 71% to 80%), specificity of 64% (95% CI, 54% to 74%), positive predictive value of 88% (95% CI, 83% to 91%), and negative predictive value of 45% (95% CI, 36% to 53%). The incomplete fascial closure group had significantly lower quality of life scores at 1 year (83.3 vs 52.5; p = 0.001), 2 years (85 vs 33.3; p = 0.003), and 3 years (86.7 vs 63.3; p = 0.049).

Conclusions: In our study, the VR cutoff of 25% was sensitive for predicting complete fascial closure for patients with ratios below this threshold. Although there is a higher likelihood of incomplete fascial closure when VR is ≥ 25%, this end point cannot be predicted reliably. Additional studies should be done to study this ratio in conjunction with other hernia-related variables to better predict this important surgical end point.
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http://dx.doi.org/10.1016/j.jamcollsurg.2021.03.009DOI Listing
April 2021

Predicting Therapeutic Response in Pediatric Ulcerative Colitis-A Journey Towards Precision Medicine.

Front Pediatr 2021 17;9:634739. Epub 2021 Feb 17.

Division of Gastroenterology, Hepatology and Nutrition, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States.

Ulcerative colitis (UC) is a disabling disease, characterized by chronic inflammation of the colon, with a rising prevalence worldwide in the pediatric age group. Although UC presents in children with varying severity, disease extent, and comorbidities, initial treatment is essentially uniform, consisting of 5-aminosalicylate drugs with corticosteroid induction for those with moderately to severely active disease. With the advent of anti-tumor necrosis factor (TNF) biologic therapy and several new biologics and small-molecule drugs for UC, precision medicine approaches to treatment are needed to more rapidly achieve sustained remission, restore quality of life, normalize development, and limit exposure to toxic corticosteroids in children with UC. Here, we review available data on clinical, biochemical, histopathologic, and molecular predictors of treatment response in UC. We also address known predictors and special treatment considerations in specific relevant scenarios such as very-early-onset UC, acute severe UC, ileal pouch anal anastomosis, and UC with concomitant primary sclerosing cholangitis. The review concludes with a prediction of how machine learning will integrate multimodal patient data to bring precision medicine to the bedside of children with UC in the future.
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http://dx.doi.org/10.3389/fped.2021.634739DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7925616PMC
February 2021

Sprouty2 limits intestinal tuft and goblet cell numbers through GSK3β-mediated restriction of epithelial IL-33.

Nat Commun 2021 02 5;12(1):836. Epub 2021 Feb 5.

The Saban Research Institute, Children's Hospital Los Angeles, Los Angeles, CA, USA.

Dynamic regulation of intestinal cell differentiation is crucial for both homeostasis and the response to injury or inflammation. Sprouty2, an intracellular signaling regulator, controls pathways including PI3K and MAPKs that are implicated in differentiation and are dysregulated in inflammatory bowel disease. Here, we ask whether Sprouty2 controls secretory cell differentiation and the response to colitis. We report that colonic epithelial Sprouty2 deletion leads to expanded tuft and goblet cell populations. Sprouty2 loss induces PI3K/Akt signaling, leading to GSK3β inhibition and epithelial interleukin (IL)-33 expression. In vivo, this results in increased stromal IL-13+ cells. IL-13 in turn induces tuft and goblet cell expansion in vitro and in vivo. Sprouty2 is downregulated by acute inflammation; this appears to be a protective response, as VillinCre;Sprouty2 mice are resistant to DSS colitis. In contrast, Sprouty2 is elevated in chronic colitis and in colons of inflammatory bowel disease patients, suggesting that this protective epithelial-stromal signaling mechanism is lost in disease.
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http://dx.doi.org/10.1038/s41467-021-21113-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7864916PMC
February 2021

Colonic Epithelial-Derived Selenoprotein P Is the Source for Antioxidant-Mediated Protection in Colitis-Associated Cancer.

Gastroenterology 2021 Apr 1;160(5):1694-1708.e3. Epub 2021 Jan 1.

Department of Medicine, Division of Gastroenterology, Vanderbilt University Medical Center, Nashville, Tennessee; Program in Cancer Biology, Vanderbilt University, Nashville, Tennessee; Center for Mucosal Inflammation and Cancer, Vanderbilt University Medical Center, Nashville, Tennessee; Veterans Affairs Tennessee Valley Health Care System, Nashville, Tennessee; Vanderbilt Ingram Cancer Center, Nashville, Tennessee. Electronic address:

Background & Aims: Patients with inflammatory bowel disease (IBD) demonstrate nutritional selenium deficiencies and are at greater risk of developing colon cancer. Previously, we determined that global reduction of the secreted antioxidant selenium-containing protein, selenoprotein P (SELENOP), substantially increased tumor development in an experimental colitis-associated cancer (CAC) model. We next sought to delineate tissue-specific contributions of SELENOP to intestinal inflammatory carcinogenesis and define clinical context.

Methods: Selenop floxed mice crossed with Cre driver lines to delete Selenop from the liver, myeloid lineages, or intestinal epithelium were placed on an azoxymethane/dextran sodium sulfate experimental CAC protocol. SELENOP loss was assessed in human ulcerative colitis (UC) organoids, and expression was queried in human and adult UC samples.

Results: Although large sources of SELENOP, both liver- and myeloid-specific Selenop deletion failed to modify azoxymethane/dextran sodium sulfate-mediated tumorigenesis. Instead, epithelial-specific deletion increased CAC tumorigenesis, likely due to elevated oxidative stress with a resulting increase in genomic instability and augmented tumor initiation. SELENOP was down-regulated in UC colon biopsies and levels were inversely correlated with endoscopic disease severity and tissue S100A8 (calprotectin) gene expression.

Conclusions: Although global selenium status is typically assessed by measuring liver-derived plasma SELENOP levels, our results indicate that the peripheral SELENOP pool is dispensable for CAC. Colonic epithelial SELENOP is the main contributor to local antioxidant capabilities. Thus, colonic SELENOP is the most informative means to assess selenium levels and activity in IBD patients and may serve as a novel biomarker for UC disease severity and identify patients most predisposed to CAC development.
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http://dx.doi.org/10.1053/j.gastro.2020.12.059DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8035252PMC
April 2021

Robo FOMO (Fear of Missing Out), But at What Cost? The Unintended Consequences of Robotics for General Surgery Operations at Rural Hospitals.

Surg Innov 2020 Dec 31;27(6):561-563. Epub 2020 Dec 31.

2569Cleveland Clinic Center for Abdominal Core Health, Cleveland Clinic, OH, USA.

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http://dx.doi.org/10.1177/1553350620984341DOI Listing
December 2020

Real-World Infliximab Pharmacokinetic Study Informs an Electronic Health Record-Embedded Dashboard to Guide Precision Dosing in Children with Crohn's Disease.

Clin Pharmacol Ther 2020 Dec 22. Epub 2020 Dec 22.

Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.

Standard-of-care infliximab dosing regimens were developed prior to the routine use of therapeutic drug monitoring and identification of target concentrations. Not surprisingly, subtherapeutic infliximab concentrations in pediatric Crohn's disease (CD) are common. The primary aim was to conduct a real-world pharmacokinetic (PK) evaluation to discover blood biomarkers of rapid clearance, identify exposure targets, and a secondary aim to translate PK modeling to the clinic. In a multicenter observational study, 671 peak and trough infliximab concentrations from 78 patients with CD were analyzed with a drug-tolerant assay (Esoterix; LabCorp, Calabasas, CA). Individual area under the curve (AUC) estimates were generated as a measure of drug exposure over time. Population PK modeling (nonlinear mixed-effect modeling) identified serum albumin, antibody to infliximab, erythrocyte sedimentation rate (ESR), and neutrophil CD64 as biomarkers for drug clearance. Week 14 and week 52 biochemical remitters (fecal calprotectin < 250 µg/g) had higher infliximab exposure (AUC) throughout induction. The optimal infliximab AUC target during induction for week 14 biochemical remission was 79,348 µg*h/mL (area under the receiver operating characteristic curve (AUROC) 0.77, [0.63-0.90], 85.7% sensitive, and 64.3% specific) with those exceeding the AUC target more likely to achieve a surgery-free week 52 biochemical remission (OR 4.3, [1.2-14.6]). Pretreatment predictors for subtherapeutic week 14 AUC included neutrophil CD64 > 6 (OR 4.5, [1.4-17.8]), ESR > 30 mm/h (OR 3.8, [1.4-11]), age < 10 years old (OR 4.2, [1.2-20]), and weight < 30 kg (OR 6.6, [2.1-25]). We created a decision-support PK dashboard with an iterative process and embedded the modeling program within the electronic health record. Model-informed precision dosing guided by real-world PKs is now available at the bedside in real-time.
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http://dx.doi.org/10.1002/cpt.2148DOI Listing
December 2020

Utilization of a quality reporting system to increase faculty participation in resident operative assessment.

Surgery 2021 03 14;169(3):483-487. Epub 2020 Dec 14.

Department of General Surgery, Cleveland Clinic, Cleveland, OH.

Background: A quality collaborative across our hospital system was initiated to track surgical outcomes. We sought to determine whether incorporating a resident operative performance assessment into this quality collaborative would increase the quantity and quality of these assessments and impact relevant milestones.

Methods: A resident operative assessment was added to a quality reporting system required to be completed by faculty at the completion of 2 operations. Three milestones directly related to operative performance were analyzed-Patient Care 3, Medical Knowledge 2, and Interpersonal and Communication Skills 3. Residents were divided in 2 groups: quality collaborative (≥10 operative assessments) and no quality collaborative (<10 operative assessments). Milestones from Spring 2019 and Fall 2019 were analyzed.

Results: Faculty participation was 86% with 407 assessments completed from February to October 2019. A difference in the rate of change in resident performance for Patient Care 3 (+0.95 vs +0.55; P = .04) and Interpersonal and Communication Skills 3 (+1.05 vs +0.52; P = .02) was observed for those residents in the quality collaborative group (n = 20) compared with baseline data.

Conclusion: Addition of an operative assessment to a mandatory quality collaborative increases faculty participation and impacts resident milestone determination. These findings highlight opportunities to find innovative and efficient methods to improve faculty engagement.
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http://dx.doi.org/10.1016/j.surg.2020.11.014DOI Listing
March 2021

The Efficacy of Liposomal Bupivacaine On Postoperative Pain Following Abdominal Wall Reconstruction: A Randomized, Double-Blind, Placebo-Controlled Trial.

Ann Surg 2020 Dec 2. Epub 2020 Dec 2.

Cleveland Clinic Center for Abdominal Core Health, Department of General Surgery, Digestive Disease and Surgery Institute, The Cleveland Clinic Foundation, 9500 Euclid Avenue, A-100, Cleveland, OH 44195.

Objective: To study the efficacy of liposomal bupivacaine on postoperative opioid requirement and pain following abdominal wall reconstruction.

Summary Background Data: Despite the widespread use of liposomal bupivacaine in transversus abdominis plane block, there is inadequate evidence demonstrating its efficacy in open abdominal wall reconstruction. We hypothesized that liposomal bupivacaine plane block would result in decreased opioid requirements compared to placebo in the first 72 hours after surgery.

Methods: This was a single-center double-blind, placebo-controlled prospective study conducted between July 2018 and November 2019. Adult patients (at least 18 years of age) undergoing open, elective, ventral hernia repairs with mesh placed in the retromuscular position were enrolled. Patients were randomized to surgeon-performed transversus abdominis plane block with liposomal bupivacaine, simple bupivacaine, or normal saline (placebo). The main outcome was opioid requirements in the first 72 hours after surgery. Secondary outcomes included total inpatient opioid use, pain scores determined using a 100 mm visual analog scale, length of hospital stay, and patient-reported quality of life.

Results: Of the 164 patients that were included in the analysis, 57 patients received liposomal bupivacaine, 55 patients received simple bupivacaine and 52 received placebo. There were no differences in the total opioid used in the first 72 hours after surgery as measured by morphine milligram equivalents when liposomal bupivacaine was compared to simple bupivacaine and placebo (325 ± 225 vs. 350 ± 284 vs. 310 ± 272, respectively, p = 0.725). Similarly, there were no differences in total inpatient opioid use, pain scores, length of stay, and patient-reported quality of life.

Conclusions: There are no apparent clinical benefits to using liposomal bupivacaine transversus abdominis plane block when compared to simple bupivacaine and placebo for open abdominal wall reconstruction.
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http://dx.doi.org/10.1097/SLA.0000000000004424DOI Listing
December 2020

Patient-Reported Outcomes of Robotic vs Laparoscopic Ventral Hernia Repair With Intraperitoneal Mesh: The PROVE-IT Randomized Clinical Trial.

JAMA Surg 2021 Jan;156(1):22-29

Cleveland Clinic Center for Abdominal Core Health, Digestive Diseases and Surgery Institute, The Cleveland Clinic Foundation, Cleveland Clinic, Cleveland, Ohio.

Importance: Despite rapid adoption of the robotic platform for ventral hernia repair with intraperitoneal mesh in the United States, there is no level I evidence comparing it with the traditional laparoscopic approach. This randomized clinical trial sought to demonstrate a clinical benefit to the robotic approach.

Objective: To determine whether robotic approach to ventral hernia repair with intraperitoneal mesh would result in less postoperative pain.

Design, Setting, And Participants: A registry-based, single-blinded, prospective randomized clinical trial at the Cleveland Clinic Center for Abdominal Core Health, Cleveland, Ohio, completed between September 2017 and January 2020, with a minimum follow-up duration of 30 days. Two surgeons at 1 academic tertiary care hospital. Patients with primary or incisional midline ventral hernias of an anticipated width of 7 cm or less presenting in the elective setting and able to tolerate a minimally invasive repair.

Interventions: Patients were randomized to a standardized laparoscopic or robotic ventral hernia repair with fascial closure and intraperitoneal mesh.

Main Outcomes And Measures: The trial was powered to detect a 30% difference in the Numerical Rating Scale (NRS-11) on the first postoperative day. Secondary end points included the Patient-Reported Outcomes Measurement Information System Pain Intensity short form (3a), hernia-specific quality of life, operative time, wound morbidity, recurrence, length of stay, and cost.

Results: Seventy-five patients completed their minimally invasive hernia repair: 36 laparoscopic and 39 robotic. Baseline demographics and hernia characteristics were comparable. Robotic operations had a longer median operative time (146 vs 94 minutes; P < .001). There were 2 visceral injuries in each cohort but no full-thickness enterotomies or unplanned reoperations. There were no significant differences in NRS-11 scores preoperatively or on postoperative days 0, 1, 7, or 30. Specifically, median NRS-11 scores on the first postoperative day were the same (5 vs 5; P = .61). Likewise, postoperative Patient-Reported Outcomes Measurement Information System 3a and hernia-specific quality-of-life scores, as well as length of stay and complication rates, were similar. The robotic platform adds cost (total cost ratio, 1.13 vs 0.97; P = .03), driven by the cost of additional operating room time (1.25 vs 0.85; P < .001).

Conclusions And Relevance: Laparoscopic and robotic ventral hernia repair with intraperitoneal mesh have comparable outcomes. The increased operative time and proportional cost of the robotic approach are not offset by a measurable clinical benefit.

Trial Registration: ClinicalTrials.gov Identifier: NCT03283982.
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http://dx.doi.org/10.1001/jamasurg.2020.4569DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7578919PMC
January 2021

Could a Small Population of Epithelial Cells Get "Tuft" With Crohn's Disease?

Authors:
Michael J Rosen

Gastroenterology 2020 12 1;159(6):2025-2027. Epub 2020 Oct 1.

Division of Gastroenterology, Hepatology and Nutrition, Cincinnati Children's Hospital Medical Center and, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio. Electronic address:

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http://dx.doi.org/10.1053/j.gastro.2020.09.037DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8015681PMC
December 2020

Achieving Target Infliximab Drug Concentrations Improves Blood and Fecal Neutrophil Biomarkers in Crohn's Disease.

Inflamm Bowel Dis 2020 Sep 18. Epub 2020 Sep 18.

Division of Gastroenterology, Hepatology and Nutrition, Cincinnati Children's Hospital Medical Center, Cincinnati, OH.

Background: The neutrophil fecal biomarkers, calprotectin (FCP) and lactoferrin (LCT), and peripheral blood neutrophil CD64 surface receptor (nCD64) are biomarkers for mucosal inflammation in inflammatory bowel disease (IBD). Although FCP has been evaluated as a biomarker for mucosal healing, cut points for LCT and nCD64 are less known. We aimed to identify the cut points for LCT and nCD64 that were associated with FCP remission, with a secondary aim to evaluate the relationship between biochemical outcomes and infliximab (IFX) trough concentrations.

Methods: We analyzed FCP, LCT, and nCD64 before and after IFX induction in a pediatric Crohn's disease (CD) cohort study. Week-14 FCP biomarker remission was defined as FCP <250 µg/g, with clinical response defined as a weighted Pediatric Crohn's Disease Activity Index <12.5 or Δ>17.5 improvement. Predictive outcomes were calculated by receiver operating characteristics (ROCs).

Results: Among 56 CD patients, ROC analysis identified an infusion 4 LCT <8.06 (area under the receiver operator characteristics [AUROC], 0.934, P < 0.001) and nCD64 <6.12 (AUROC, 0.76, P = 0.02) as the ideal cut points for week-14 FCP biomarker remission. End of induction IFX-trough of >9.4 µg/mL (AUROC, 0.799, P = 0.002) and >11.5 µg/mL (AUROC, 0.835, P = 0.003) were associated with a FCP <250 and FCP <100, respectively. We found patients achieving end of induction trough >5 µg/mL had a median FCP improvement (dose 1 to dose 4) of 90% compared with a median of 35% with levels <5 µg/mL (P = 0.024) with a similar median reduction in nCD64 (48% vs 20%, P = 0.031).

Conclusions: This study establishes cut points in neutrophil stool and blood biomarkers for both biochemical remission and therapeutic trough levels following induction therapy. Further studies that evaluate pharmacodynamic biomarker targets for endoscopic and histologic healing are warranted.
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http://dx.doi.org/10.1093/ibd/izaa241DOI Listing
September 2020

Effect modification of resident autonomy and seniority on perioperative outcomes in laparoscopic cholecystectomy.

Surg Endosc 2020 Jul 8. Epub 2020 Jul 8.

Digestive Disease and Surgery Institute, Cleveland Clinic, Cleveland, OH, USA.

Background: Resident operative involvement is an integral aspect of general surgery residency training. However, current data examining the effect of resident autonomy on perioperative outcomes remain limited.

Methods: Patient and operator-specific data were collected from 344 adult laparoscopic cholecystectomies at a tertiary academic institution and its regional affiliates between 2018 and 2019. Multivariate modeling compared postoperative outcomes between cases completed with or without resident involvement and its effect modification by resident seniority and autonomy per Zwisch scale. Outcomes include 30-day postoperative complications, hospital readmission rate, and operative time.

Results: Multivariate analysis revealed resident involvement in laparoscopic cholecystectomy did not significantly change odds of 30-day postoperative complications (OR 2.52, p = 0.185, 95% CI 0.64-9.92) or hospital readmission (OR 1.61, p = 0.538, 95% CI 0.36-7.23). Operative time is significantly increased compared to faculty-only cases (IRR 1.37, p < 0.001, 95% CI 1.26-1.48). While accounting for case difficulty and resident performance evaluated by SIMPL criteria, stratification by resident autonomy measured by Zwisch scale or seniority reveal no effect modification on 30-day postoperative complications, readmissions, or operative time. The effect of resident involvement on longer relative rates of operative time loses its significance in supervision-only cases (IRR 1.18, p = 0.069, 95% CI 0.99-1.41).

Conclusion: While resident involvement and autonomy are associated with significantly longer operative times in laparoscopic cholecystectomy, their lack of significant effect on postoperative outcomes argues strongly for continued resident involvement and supervised operative independence.
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http://dx.doi.org/10.1007/s00464-020-07780-5DOI Listing
July 2020

Registry-Based Randomized Controlled Trials: A New Paradigm for Surgical Research.

J Surg Res 2020 11 30;255:428-435. Epub 2020 Jun 30.

Department of General Surgery, Digestive Disease and Surgery Institute, Cleveland Clinic Foundation, Cleveland, Ohio.

Background: Randomized controlled trials (RCTs) are the gold standard to establish evidence for surgical practice but can be hindered by high costs, complexity, and time requirements. Recently, observational registries have been leveraged as platforms for clinical trials to address these limitations, though few registry-based surgical RCTs have been conducted. Here, we present our group's approach to surgical registry-based RCTs and early results.

Materials And Methods: To facilitate these trials, we focused on registry integration into surgeons' workflows, routine collection of patient-reported outcomes at clinic visits, and pragmatic trial design featuring broad inclusion criteria and standard of care follow-up. These features maximize generalizability and facilitate follow-up by minimizing visits and tests outside of normal practice.

Results: Since 2017, our group has completed enrollment in 4 registry-based RCTs with another 5 trials ongoing. Of these, 4 trials have been multicenter. Over 1000 patients have been enrolled in these studies, with follow-up rates of 90% or greater. Most of these trials are on track to complete enrollment in approximately 2 y from their start date. Beyond salary support, resource utilization is low. None of our trials has been terminated due to lack of resources or futility.

Conclusions: Registry-based RCTs allow for efficient conduct of pragmatic surgical trials. Thoughtful study design, registry integration into surgeons' routines, and a team culture embracing research are paramount. We believe registry-based trials are the future of affordable, high-level, prospective surgical research.
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http://dx.doi.org/10.1016/j.jss.2020.05.069DOI Listing
November 2020

Pediatric Patient With Ulcerative Colitis-Associated Bronchiectasis.

ACG Case Rep J 2020 Apr 7;7(4):e00365. Epub 2020 Apr 7.

Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH.

We report a unique case of ulcerative colitis-associated bronchiectasis in a pediatric patient 6 years after colectomy. The patient presented with a chronic cough and had a computed tomography demonstrating bronchiectasis. She was treated with sputum expectoration (airway clearance) via chest physiotherapy and pulse-dose steroids with a prolonged oral taper. Her initial response was excellent; however, she experienced a recurrence of symptoms with de-escalation of airway clearance. Pulmonary extraintestinal manifestations of inflammatory bowel disease are most often diagnosed later in life. Both the severity of this patient's presentation and her age are unique to this case.
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http://dx.doi.org/10.14309/crj.0000000000000365DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7224709PMC
April 2020

Patient-reported opioid use after open abdominal wall reconstruction: How low can we go?

Surgery 2020 07 2;168(1):141-146. Epub 2020 Jun 2.

Center for Abdominal Core Health, Digestive Disease and Surgery Institute, Cleveland Clinic Foundation, Cleveland, OH.

Background: Little data exist to inform discharge opioid prescribing for patients undergoing abdominal wall reconstruction. The aim of this study was to evaluate postoperative, patient-reported opioid use after abdominal wall reconstruction. We hypothesized that the majority of patients undergoing open abdominal wall reconstruction would require between 16 and 30 opioid tablets after discharge.

Methods: Postoperative, patient-reported opioid use was collected prospectively for all patients undergoing elective, open abdominal wall reconstruction at a single high-volume center. All opioid medications were converted to an equivalent number of 5 mg oxycodone tablets. The primary outcome was the total number of opioid tablets taken within 30 days of hospital discharge after abdominal wall reconstruction.

Results: Ninety-eight patients were included. Median hernia width was 15 cm (interquartile range 12-19), 42% were recurrences, and all underwent transversus abdominis release. At the 30-day follow-up visit, 24% reported no postdischarge opioid use, and 76% reported taking 15 tablets or fewer. Of the 23 patients who used no opioids on the day before discharge, 16 (70%) reported taking no opioids after discharge.

Conclusion: Most patients reported taking fewer opioid tablets than prescribed and fewer than our hypothesis within 30 days of abdominal wall reconstruction. Opioid use on the day before discharge may allow for prognostication of outpatient opioid requirements to prevent overprescribing.
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http://dx.doi.org/10.1016/j.surg.2020.04.008DOI Listing
July 2020

Effect of a Practice-wide Anti-TNF Proactive Therapeutic Drug Monitoring Program on Outcomes in Pediatric Patients with Inflammatory Bowel Disease.

Inflamm Bowel Dis 2021 Mar;27(4):482-492

Division of Gastroenterology, Hepatology, and Nutrition, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.

Background: Reports on the feasibility and effectiveness of translating proactive, antitumor necrosis factor (TNF) therapeutic drug monitoring (TDM) for inflammatory bowel disease into practice-wide quality improvement (QI) are lacking. We aimed to determine whether a TDM QI program improved outcomes at a large academic pediatric gastroenterology practice.

Methods: We instituted local anti-TNF TDM practice guidelines to proactively monitor and optimize drug levels (goal >5 μg/mL). We conducted a retrospective single-center cohort analysis of patient outcomes before (pre-TDM) and after (post-TDM) guideline institution and assessed the independent effect by multivariable regression. Primary outcome was sustained clinical remission (SCR22-52), defined as physician global assessment (PGA) of inactive from 22 to 52 weeks and off corticosteroids at 52 weeks.

Results: We identified 108 pre-TDM and 206 post-TDM patients. The SCR22-52 was achieved in 42% of pre-TDM and 59% of post-TDM patients (risk difference, 17.6%; 95% CI, 5.4-29%; P = 0.004). The post-TDM group had an increased adjusted odds of achieving SCR22-52 (odds ratio, 2.03; 95% CI, 1.27-3.26; P = 0.003). The adjusted risk of developing high titer antidrug antibodies (ADAs) was lower in the post-TDM group (hazard ratio, 0.18; 95% CI, 0.09-0.35; P < 0.001). Although the risk of anti-TNF cessation for any reason was not significantly different, there was a lower adjusted risk of cessation related to any detectable ADA in the post-TDM group (hazard ratio, 0.45; 95% CI, 0.26-0.77; P = 0.003).

Conclusions: A practice-wide proactive anti-TNF TDM QI program improved key clinical outcomes at our institution, including sustained clinical remission, incidence of high titer ADA, and anti-TNF cessation related to ADA.
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http://dx.doi.org/10.1093/ibd/izaa102DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7957222PMC
March 2021

Favorable Outcomes and Anti-TNF Durability After Addition of an Immunomodulator for Anti-Drug Antibodies in Pediatric IBD Patients.

Inflamm Bowel Dis 2021 Mar;27(4):507-515

Division of Gastroenterology, Hepatology and Nutrition, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, United States.

Background: Anti-drug antibodies (ADAs) to anti-tumor necrosis factor alpha (anti-TNF) drugs are associated with increased drug clearance and loss of response. We aimed to assess the effectiveness of starting an immunomodulator (IM) drug in patients with newly detected ADAs on anti-TNF monotherapy.

Methods: We reviewed the medical records of pediatric patients with inflammatory bowel disease on infliximab or adalimumab monotherapy with first-time detection of significant ADAs between 2014 and 2018. Patients who started an IM within 3 months of ADA detection were compared with those who did not (No-IM). Outcomes included steroid-free clinical and biochemical remission on the same anti-TNF , anti-TNF durability, and ADA reversal.

Results: We identified 89 patients with ADAs: 30 IM patients and 59 No-IM patients. The initial anti-TNF was stopped shortly after ADA detection in 36% of the No-IM patients vs none of the IM patients, driving longer survival on the initial anti-TNF in the IM group (P = 0.005). At 12 months, steroid-free clinical and biochemical remission on the same anti-TNF occurred in 53.9% of the IM group vs 26.8% in the No-IM group (P = 0.025). Drug levels rose higher (P = 0.003) and ADA levels fell farther (P = 0.037) in the IM group than in the No-IM group. Baseline ADA level predicted ADA reversal in the No-IM patients with an area under the receiver operating characteristic of 0.79 (P = 0.006). An ADA level <329 ng/mL had a 76.2% sensitivity and an 83.3% specificity for ADA reversal without IM.

Conclusions: Pediatric patients with inflammatory bowel disease on anti-TNF monotherapy who started an IM for significant ADA levels exhibited longer anti-TNF durability and a higher likelihood of steroid-free clinical and biochemical remission on the same anti-TNF. Patients not treated with an IM were unlikely to reverse ADAs >329 ng/mL.
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http://dx.doi.org/10.1093/ibd/izaa108DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7957223PMC
March 2021

A Micro-longitudinal Approach to Measuring Medication Adherence in Pediatric Inflammatory Bowel Diseases.

J Pediatr Gastroenterol Nutr 2020 09;71(3):366-370

Center for Adherence and Self-Management, Behavioral Medicine and Clinical Psychology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH.

Measuring medication adherence in pediatric inflammatory bowel diseases (IBD) is challenging because of complexities in personalized treatment regimens and increased use of biologic mono- and combination therapy. Objective measurement of adherence via electronic monitoring is the gold standard; however, it is not useful for daily monitoring when multiple medication formulations (eg, pills, injections, infusions) as well as vitamins/supplements are prescribed. Although validated subjective measures are available, they are not designed for daily use and do not capture day-to-day variation in adherence. In the following article, a new approach to measuring adherence regardless of a patient's specific medication regimen is presented. Utilizing a micro-longitudinal design, 30 days of daily self-reported medication adherence data was collected from youth with IBD via text message. Results reflect mean adherence rates from studies utilizing pill counts and electronic monitoring, suggesting promise for the use of self-reported daily diaries to assess medication adherence in pediatric IBD.
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http://dx.doi.org/10.1097/MPG.0000000000002778DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8025293PMC
September 2020

The Diagnostic Utility of Splenectomy in Idiopathic Splenomegaly.

World J Surg 2020 09;44(9):2959-2964

Department of General Surgery, Digestive Disease and Surgery Institute, Cleveland Clinic, 9500 Euclid Avenue, Desk A100, Cleveland, OH, 44195, USA.

Introduction: With increasing frequency, patients with idiopathic splenomegaly are referred to surgeons for splenectomy. We evaluated the diagnostic utility of splenectomy and feasibility of a minimally invasive approach in the face of idiopathic splenomegaly.

Methods: We retrospectively reviewed 68 patients who underwent splenectomy for idiopathic splenomegaly. The primary endpoint was the rate of definitive diagnosis based on final surgical pathology of the removed spleen.

Results: Preoperative workup included a bone marrow biopsy and peripheral blood smear in 93% and 100% of patients, respectively, with none having lymphadenopathy warranting biopsy. Splenectomy provided a definitive diagnosis for 44 (64.7%) patients. Of these, 34 (50%) patients had an underlying malignancy, of which more than half were splenic marginal zone lymphoma. There were 33 (48.5%) laparoscopic, 23 (33.8%) open, 10 (14.7%) laparoscopic converted to open, and two (2.9%) laparoscopic hand-assist cases. Conversion to open was due to splenic size [median craniocaudal length 21.8 cm (cm)] in eight and staple line bleeding at the splenic hilum in two patients. Overall, the laparoscopic approach was completed in patients with a smaller splenic size compared to open (median craniocaudal length 15.2 vs. 26.0 cm, p < 0.0001). The open group had one (1.5%) intra-operative mortality due to uncontrollable hemorrhage. Thirty-day complication rates were similar for laparoscopic and open approaches (p = 0.10).

Conclusion: Splenectomy is an effective diagnostic modality in determining a pathologic cause for splenomegaly in this patient population. Laparoscopic splenectomy can be performed safely in appropriate cases with craniocaudal splenic size having the largest influence on surgical approach.
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http://dx.doi.org/10.1007/s00268-020-05566-3DOI Listing
September 2020

Detection of microbial cell-free DNA in maternal and umbilical cord plasma in patients with chorioamnionitis using next generation sequencing.

PLoS One 2020 15;15(4):e0231239. Epub 2020 Apr 15.

Eli and Edythe Broad Center of Regeneration Medicine, University of California, San Francisco, California, United States of America.

Background: Chorioamnionitis has been linked to spontaneous preterm labor and complications such as neonatal sepsis. We hypothesized that microbial cell-free (cf) DNA would be detectable in maternal plasma in patients with chorioamnionitis and could be the basis for a non-invasive method to detect fetal exposure to microorganisms.

Objective: The purpose of this study was to determine whether next generation sequencing could detect microbial cfDNA in maternal plasma in patients with chorioamnionitis.

Study Design: Maternal plasma (n = 94) and umbilical cord plasma (n = 120) were collected during delivery at gestational age 28-41 weeks. cfDNA was extracted and sequenced. Umbilical cord plasma samples with evidence of contamination were excluded. The prevalence of microorganisms previously implicated in choriomanionitis, neonatal sepsis and intra-amniotic infections, as described in the literature, were examined to determine if there was enrichment of these microorganisms in this cohort. Specific microbial cfDNA associated with chorioamnionitis was first detected in umbilical cord plasma and confirmed in the matched maternal plasma samples (n = 77 matched pairs) among 14 cases of histologically confirmed chorioamnionitis and one case of clinical chorioamnionitis; 63 paired samples were used as controls. A correlation of rank of a given microorganism across maternal plasma and matched umbilical cord plasma was used to assess whether signals found in umbilical cord plasma were also present in maternal plasma.

Results: Microbial DNA sequences associated with clinical and/or histological chorioamnionitis were enriched in maternal plasma in cases with suspected chorioamnionitis when compared to controls (12/14 microorganisms, p = 0.02). Analysis of the microbial cfDNA in umbilical cord plasma among the 1,251 microorganisms detectable with this assay identified Streptococcus mitis, Ureaplasma spp., and Mycoplasma spp. in cases of suspected chorioamnionitis. This assay also detected cfDNA from Lactobacillus spp. in controls. Comparison between maternal plasma and umbilical cord plasma confirmed these signatures were also present in maternal plasma. Unbiased analysis of microorganisms with significantly correlated signal between matched maternal plasma and umbilical cord plasma identified the above listed 3 microorganisms, all of which have previously been implicated in patients with chorioamnionitis (Mycoplasma hominis p = 0.0001; Ureaplasma parvum p = 0.002; Streptococcus mitis p = 0.007). These data show that the pathogen signal relevant for chorioamnionitis can be identified in both maternal and umbilical cord plasma.

Conclusion: This is the first report showing the detection of relevant microbial cell-free cfDNA in maternal plasma and umbilical cord plasma in patients with clinical and/or histological chorioamnionitis. These results may lead to the development of a specific assay to detect perinatal infections for targeted therapy to reduce early neonatal sepsis complications.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0231239PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7159194PMC
July 2020

Robotic Inguinal vs Transabdominal Laparoscopic Inguinal Hernia Repair: The RIVAL Randomized Clinical Trial.

JAMA Surg 2020 05;155(5):380-387

Cleveland Clinic Center for Abdominal Core Health, Digestive Diseases and Surgery Institute, Cleveland Clinic, The Cleveland Clinic Foundation, Cleveland, Ohio.

Importance: Despite rapid adoption of the robotic platform for inguinal hernia repair in the US, to date, no level I trials have ever compared robotic inguinal hernia repair to laparoscopic repair. This multicenter randomized clinical trial is the first to compare the robotic platform to laparoscopic approach for minimally invasive inguinal hernia repair.

Objective: To determine whether the robotic approach to inguinal hernia repair results in improved postoperative outcomes compared with traditional laparoscopic inguinal hernia repairs.

Design, Setting, And Participants: This multicenter, single-blinded, prospective randomized clinical pilot study was conducted from April 2016 to April 2019, with a follow-up duration of 30 days in 6 academic and academic-affiliated sites. Enrolled in this study were 113 patients with a unilateral primary or recurrent inguinal hernia. After exclusions 102 remained for analysis.

Interventions: Standard laparoscopic transabdominal preperitoneal repair or robotic transabdominal preperitoneal repair.

Main Outcomes And Measures: Main outcomes included postoperative pain, health-related quality of life, mobility, wound morbidity, and cosmesis. Secondary outcomes included cost, surgeon ergonomics, and surgeon mental workload. A primary outcome was not selected because this study was designed as a pilot study. The hypothesis was formulated prior to data collection.

Results: A total of 102 patients were included in the study (54 in the laparoscopic group, mean [SD] age, 57.2 [13.3] years and 48 [88.9%] male; 48 in the robotic group, mean [SD] age, 56.1 [14.1] years and 44 [91.6%] male). There were no differences at the preoperative, 1-week, or 30-day points between the groups in terms of wound events, readmissions, pain as measured by the Visual Analog Scale, or quality of life as measured by the 36-Item Short Form Health Survey. Compared with traditional laparoscopic inguinal hernia repair, robotic transabdominal preperitoneal repair was associated with longer median (interquartile range) operative times (75.5 [59.0-93.8] minutes vs 40.5 [29.2-63.8] minutes, respectively; P < .001), higher median (interquartile range) cost ($3258 [$2568-$4118] vs $1421 [$1196-$1930], respectively; P < .001), and higher mean (SD) frustration levels on the NASA Task Load Index Scale (range, 1-100, with lower scores indicating lower cognitive workload) (32.7 [23.5] vs 20.1 [19.2], respectively; P = .004). There were no differences in ergonomics of the surgeons between the groups as measured by the Rapid Upper Limb Assessment instrument.

Conclusions And Relevance: Results of this study showed no clinical benefit to the robotic approach to straightforward inguinal hernia repair compared with the laparoscopic approach. The robotic approach incurred higher costs and more operative time compared with the laparoscopic approach, with added surgeon frustration and no ergonomic benefit to surgeons.

Trial Registration: ClinicalTrials.gov Identifier: NCT02816658.
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http://dx.doi.org/10.1001/jamasurg.2020.0034DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7081145PMC
May 2020

Obstructive sleep apnea and CPAP therapy alter distinct transcriptional programs in subcutaneous fat tissue.

Sleep 2020 06;43(6)

Center for Sleep and Cardiovascular Outcomes Research, University of Pittsburgh, Pittsburgh, PA.

Obstructive sleep apnea (OSA) has been linked to dysregulated metabolic states, and treatment of sleep apnea may improve these conditions. Subcutaneous adipose tissue is a readily samplable fat depot that plays an important role in regulating metabolism. However, neither the pathophysiologic consequences of OSA nor the effects of continuous positive airway pressure (CPAP) in altering this compartment's molecular pathways are understood. This study aimed to systematically identify subcutaneous adipose tissue transcriptional programs modulated in OSA and in response to its effective treatment with CPAP. Two subject groups were investigated: Study Group 1 was comprised of 10 OSA and 8 controls; Study Group 2 included 24 individuals with OSA studied at baseline and following CPAP. For each subject, genome-wide gene expression measurement of subcutaneous fat was performed. Differentially activated pathways elicited by OSA (Group 1) and in response to its treatment (Group 2) were determined using network and Gene Set Enrichment Analysis (GSEA). In Group 2, treatment of OSA with CPAP improved apnea-hypopnea index, daytime sleepiness, and blood pressure, but not anthropometric measures. In Group 1, GSEA revealed many up-regulated gene sets in OSA subjects, most of which were involved in immuno-inflammatory (e.g. interferon-γ signaling), transcription, and metabolic processes such as adipogenesis. Unexpectedly, CPAP therapy in Group 2 subjects was also associated with up-regulation of several immune pathways as well as cholesterol biosynthesis. Collectively, our findings demonstrate that OSA alters distinct inflammatory and metabolic programs in subcutaneous fat, but these transcriptional signatures are not reversed with short-term effective therapy.
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http://dx.doi.org/10.1093/sleep/zsz314DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7294406PMC
June 2020

Response to letter to the editor: Emergency groin hernia repair: A single center 10-year experience.

Surgery 2020 04 22;167(4):772-773. Epub 2019 Nov 22.

Center for Abdominal Core Health, Digestive Disease and Surgery Institute, Cleveland Clinic Foundation, OH.

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http://dx.doi.org/10.1016/j.surg.2019.10.005DOI Listing
April 2020

Surgical treatment for chronic postoperative inguinal pain-short term outcomes of a specialized center.

Am J Surg 2020 03 15;219(3):425-428. Epub 2019 Oct 15.

Center for Abdominal Core Health, Digestive Disease and Surgery Institute, Cleveland Clinic Foundation, Cleveland, OH, USA.

Background: Chronic postoperative inguinodynia is a challenging long-term complication after inguinal hernia repair. Surgery may be an option for patients who are refractory to non-operative measures. We aim to evaluate the short-term outcomes of surgical treatment for chronic inguinodynia at our institution.

Methods: Consecutive patients undergoing surgical treatment for chronic groin pain were identified in a prospectively maintained database. Outcomes included operative details, intra- and postoperative complications, pain scores, and patient satisfaction.

Results: 29 patients were included in the study. All patients were refractory to multimodal pain management. The median pain score on presentation was 8 (IQR 7-10), and after a median follow-up of 6 months (IQR 4-11), there was a statistically significant reduction in pain scores (median 2, IQR 2-6, p < 0.001). Fifty-five percent of patient were pain free or almost pain free and 93 percent reported they would undergo the same operation again.

Conclusions: Chronic groin pain is a complex problem with no universal solution. In our experience, surgical treatment significantly decreased short-term pain scores.
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http://dx.doi.org/10.1016/j.amjsurg.2019.10.020DOI Listing
March 2020

Elevated Pretreatment Plasma Oncostatin M Is Associated With Poor Biochemical Response to Infliximab.

Crohns Colitis 360 2019 Oct 19;1(3):otz026. Epub 2019 Aug 19.

Division of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati Children's Hospital Medical Center, Cincinnati, OH.

Background: We hypothesized that elevations of plasma Oncostatin M (OSM) would be associated with infliximab nonresponse.

Methods: Plasma OSM was measured in Crohn disease patients pre-infliximab with biochemical response (>50% reduction in fecal calprotectin) as the primary outcome.

Results: The median OSM in biochemical responders was 86 (69-148) pg/mL compared with 166 (74-1766) pg/mL in nonresponders ( = 0.03). Plasma OSM > 143.5 pg/mL was 71% sensitive and 78% specific for biochemical nonresponse (area under the curve 0.71). Early biochemical nonremission was also associated with an elevated neutrophil CD64 expression (odds ratio 8.9, = 0.011).

Conclusions: Elevated preinfliximab plasma OSM and nCD64 surface expression were both associated with poor biochemical outcomes.
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http://dx.doi.org/10.1093/crocol/otz026DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6798793PMC
October 2019

What Surgeons Need to Know About the Bouffant Scandal.

JAMA Surg 2019 11;154(11):989-990

Cleveland Clinic Center for Abdominal Core Health, Department of General Surgery, Cleveland Clinic, Cleveland, Ohio.

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http://dx.doi.org/10.1001/jamasurg.2019.2107DOI Listing
November 2019

Harnessing the Power of Collaboration for Postmarket Surveillance of Hernia Mesh Devices.

Ann Surg 2020 02;271(2):221-222

Cleveland Clinic Center for Abdominal Core Health, Department of General Surgery, The Cleveland Clinic Foundation, Cleveland, OH.

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http://dx.doi.org/10.1097/SLA.0000000000003437DOI Listing
February 2020

Improved Population Pharmacokinetic Model for Predicting Optimized Infliximab Exposure in Pediatric Inflammatory Bowel Disease.

Inflamm Bowel Dis 2020 02;26(3):429-439

Division of Gastroenterology, Hepatology, and Nutrition, Cincinnati, Ohio, USA.

Background: Many pediatric patients with inflammatory bowel disease (IBD) lose response to infliximab (IFX) within the first year, and achieving a minimal target IFX trough concentration is associated with higher remission rates and longer durability. Population pharmacokinetic (PK) modeling can predict trough concentrations for individualized dosing. The object of this study was to refine a population PK model that accurately predicts individual IFX exposure during maintenance therapy using longitudinal real-practice data.

Methods: We exported data from the electronic health records of pediatric patients with IBD treated with originator IFX at a single center between January 2011 and March 2017. Subjects were divided into discovery and validation cohorts. A population PK model was built and then validated.

Results: We identified 228 pediatric patients with IBD who received IFX and had at least 1 drug concentration measured, including 135 and 93 patients in the discovery and validation cohorts, respectively. Weight, albumin, antibodies to IFX (ATI) detected by a drug-tolerant assay, and erythrocyte sedimentation rate (ESR) were identified as covariates significantly associated with IFX clearance and incorporated into the model. The model exhibited high accuracy for predicting target IFX trough concentrations with an area under the receiver operating characteristic curve (AUROC) of 0.86 (95% confidence interval [CI], 0.81-0.91) for population-based predictions without prior drug-level input. Accuracy increased further for individual-based predictions when prior drug levels were known, with an AUROC of 0.93 (95% CI, 0.90-0.97).

Conclusions: A population PK model utilizing weight, albumin, ordinal drug-tolerant ATI, and ESR accurately predicts IFX trough concentrations during maintenance therapy in real-practice pediatric patients with IBD. This model, which incorporates dynamic clinical information, could be used for individualized dosing decisions to increase response durability.
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http://dx.doi.org/10.1093/ibd/izz143DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7171445PMC
February 2020