Publications by authors named "John McMichael"

53 Publications

Is Intestinal Diversion an Effective Treatment for Distal Crohn's Disease?

Inflamm Bowel Dis 2021 Jun 2. Epub 2021 Jun 2.

Division of Colon and Rectal Surgery, Cedars-Sinai Medical Center, Los Angeles, California, USA.

Background: Fecal diversion with an ileostomy is selectively used in cases of medically refractory Crohn's proctocolitis or advanced perianal disease. The aim of this study was to evaluate clinical improvement after fecal diversion in Crohn's disease (CD) and factors associated with clinical improvement.

Methods: A retrospective chart review of adult CD patients undergoing ileostomy formation for distal disease between 2000 and 2019 at 2 CD referral centers was conducted. The primary outcome was the rate of clinical improvement with diversion that allowed for successful restoration of intestinal continuity. Secondary outcomes included the rate of clinical and endoscopic improvement after fecal diversion, ileostomy morbidity, need for subsequent total proctocolectomy and end ileostomy, and factors associated with a clinical response to fecal diversion.

Results: A total of 132 patients with a median age of 36 years (interquartile range, 25-49) were included. Mean duration of disease was 16.2 years (10.4) years. Indication for surgery was medically refractory proctocolitis with perianal disease (n = 59; 45%), perianal disease alone (n = 24; 18%), colitis (n = 37; 28%), proctitis (n = 4; 3%), proctocolitis alone (n = 4; 3%), and ileitis with perianal disease (n = 4; 3%). Medications used before surgery included corticosteroids (n = 59; 45%), immunomodulators (n = 55; 42%) and biologics (n = 82; 62%). The clinical and endoscopic response to diversion was 43.2% (n = 57) and 23.9% (n = 16). At a median follow-up of 35.3 months (interquartile range, 10.6-74.5), 25 patients (19%) had improved and had ileostomy reversal, but 86 (65%) did not improve, with 50 (38%) undergoing total proctocolectomy for persistent symptoms. There were no significant predictors of clinical improvement.

Conclusions: The use of a "temporary" ileostomy is largely ineffective in achieving clinical response.
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http://dx.doi.org/10.1093/ibd/izab126DOI Listing
June 2021

Anal Squamous Cell Carcinoma in Ulcerative Colitis: Can Pouches Withstand Traditional Treatment Protocols?

Dis Colon Rectum 2021 Apr 26. Epub 2021 Apr 26.

Department of Colorectal Surgery, Digestive Disease Surgical Institute, Cleveland Clinic, Cleveland, Ohio General Surgery, Digestive Disease Surgical Institute, Cleveland Clinic, Cleveland, Ohio Department of Gastroenterology, Digestive Disease Surgical Institute, Cleveland Clinic, Cleveland, Ohio.

Background: Anal squamous cell carcinoma has rarely reported in ulcerative colitis.

Objective: Understand the prognosis of anal squamous cell carcinoma in the setting of ulcerative colitis.

Design: Retrospective review.

Setting: Referral center.

Patients: Adult patients with both ulcerative colitis (556.9/K51.9) and anal squamous cell carcinoma (154.3/C44.520) between January 1, 2000 to August 1, 2019.

Main Outcomes Measures: Treatment and survival of anal squamous cell carcinoma.

Results: Seventeen adult patients with ulcerative colitis and anal dysplasia and/or anal squamous cell carcinoma were included out of 13,499 ulcerative colitis patients treated; 6 had a diagnosis of anal squamous cell carcinoma, 8 had high grade squamous intraepithelial lesions, and 3 had low grade squamous intraepithelial lesions. There were 4 males (23%) and median age of 55 years (range, 32-69) years. At diagnosis, 6 had an ileal pouch anal anastomosis of which 5 had active pouchitis, 1 had an ileorectal anastomosis with active proctitis, 1 had a Hartman's stump with disuse proctitis, 5 had pancolitis, and 4 had left sided colitis. Of the 6 with anal squamous cell carcinoma, all received 5-FU and mitomycin C with external beam radiation therapy. Four patients had an ileal pouch anal anastomosis, all of whom required intestinal diversion or pouch excision due to treatment intolerance. At a median follow-up of 60 months, three patients experienced mortality: one at 0 months (treatment related myocardial infarction), one at 60 months (metastatic anal squamous cell carcinoma), and one at 129 months (malignant peripheral nerve sheath tumor); the remaining had no residual disease.

Limitations: Retrospective, small number of patients.

Conclusion: Anal squamous cell carcinoma in the setting of ulcerative colitis is extremely rare. In the setting of IPAA, diversion may be necessary to prevent radiation intolerance. Careful examination of the perianal region should be performed at the time of surveillance endoscopy. See Video Abstract at http://links.lww.com/DCR/B582.
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http://dx.doi.org/10.1097/DCR.0000000000002011DOI Listing
April 2021

Factors that Minimize Curative Resection for Gallbladder Adenocarcinoma: an Analysis of Clinical Decision-Making and Survival.

J Gastrointest Surg 2021 Feb 9. Epub 2021 Feb 9.

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

Background: Gallbladder adenocarcinoma has a poor prognosis as it is often diagnosed incidentally, and patients have a high risk for residual and occult metastatic disease. Expert guidelines recommend definitive surgery for ≥T1b tumors; however, surgical management is inconsistent. This study evaluates the factors that affect the completion of radical resection with portal lymphadenectomy and its impact on survival.

Methods: A retrospective review of patients who underwent surgery for gallbladder cancer from 2008 to 2017 at an academic institution was performed. Patients were analyzed based on whether they underwent definitive surgical resection. Patient factors and clinical decision-making were analyzed; overall survival was compared using Kaplan-Meier analysis.

Results: Seventy-five patients with ≥T1b tumors were identified, of who 32 (42.7%) underwent definitive resection. Fifty-four (72%) patients had gallbladder cancer identified as an incidental diagnosis following laparoscopic cholecystectomy. Among patients who did not undergo definitive resection, the underlying factors were varied. Only 24 (55.8%) patients in the non-definitive resection group were seen by surgical oncology. Among patients who underwent re-operation for definitive resection, 12 (38.7%) were upstaged on final pathology. Of the 43 patients who did not undergo definitive resection, 4 (9.3%) had metastatic disease identified during attempted re-resection. Patients who underwent definitive resection had a significantly longer median overall survival compared to those who did not (4.3 v. 1.9 years, p = 0.02).

Conclusions: Patients undergoing definitive resection have a significantly improved survival, including as part of a re-operative strategy. Universal referral to a surgical specialist is a modifiable factor resulting in increased definitive resection rates.
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http://dx.doi.org/10.1007/s11605-021-04942-1DOI Listing
February 2021

Effects of cannabis oil extract on immune response gene expression in human small airway epithelial cells (HSAEpC): implications for chronic obstructive pulmonary disease (COPD).

J Cannabis Res 2020 Jan 31;2(1). Epub 2020 Jan 31.

Beech Tree Labs Inc., 1 Virginia Ave, Suite 103, Providence, RI, 02905, USA.

Background: Chronic obstructive pulmonary disease (COPD) is commonly associated with both a pro-inflammatory and a T-helper 1 (Th1) immune response. It was hypothesized that cannabis oil extract can alleviate COPD symptoms by eliciting an anti-inflammatory Th2 immune response. Accordingly, the effects of cannabis oil extract on the expression of 84 Th2 and related immune response genes in human small airways epithelial cells (HSAEpC) were investigated.

Methods: HSAEpC from a single donor were treated with three dilutions of a standardized cannabis oil extract (1:400, 1:800 and 1:1600) along with a solvent control (0.25% [2.5 ul/ml] ethanol) for 24 h. There were four replicates per treatment dilution, and six for the control. RNA isolated from cells were employed in pathway-focused quantitative polymerase chain reaction (qPCR) microarray assays.

Results: The extract induced significant (P < 0.05) changes in expression of 37 tested genes. Six genes (CSF2, IL1RL1, IL4, IL13RA2, IL17A and PPARG) were up-regulated at all three dilutions. Another two (CCL22 and TSLP) were up-regulated while six (CLCA1, CMA1, EPX, LTB4R, MAF and PMCH) were down-regulated at the 1:400 and 1:800 dilutions. The relationship of differentially-expressed genes of interest to biologic pathways was explored using the Database for Annotation, Visualization and Integrated Discovery (DAVID).

Conclusions: This exploratory investigation indicates that cannabis oil extract may affect expression of specific airway epithelial cell genes that could modulate pro-inflammatory or Th1 processes in COPD. These results provide a basis for further investigations and have prompted in vivo studies of the effects of cannabis oil extract on pulmonary function.

Trial Registration: NONE (all in vitro experiments).
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http://dx.doi.org/10.1186/s42238-019-0014-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7819312PMC
January 2020

Clinical Risk Prediction Model for Neoadjuvant Therapy in Resectable Esophageal Adenocarcinoma.

J Clin Gastroenterol 2021 Jan 5;Publish Ahead of Print. Epub 2021 Jan 5.

Department of Gastroenterology and Hepatology, Center of Excellence for Barrett's Esophagus, Cleveland Clinic Departments of Internal Medicine Quantitative Health Sciences General Surgery Thoracic and Cardiovascular Surgery, Cleveland Clinic, Cleveland Department of Hematology and Oncology, University of Cincinnati, Cincinnati, OH Department of Gastroenterology and Hepatology, Baylor College of Medicine, Houston, TX Section of General Internal Medicine, Tulane Medical Center, New Orleans, LA.

Goals And Background: Clinical staging with endoscopic ultrasound (EUS) and positron emission tomography (PET) is used to identify esophageal adenocarcinoma (EAC) patients with locally advanced disease and therefore, benefit from neoadjuvant therapy. However, EUS is operator dependent and subject to interobserver variability. Therefore, we aimed to identify clinical predictors of locally advanced EAC and build a predictive model that can be used as an adjunct to current staging methods.

Study: This was a cross-sectional study of patients with EAC who underwent preoperative staging with EUS and PET scan followed by definitive therapy at our institution from January 2011 to December 2017. Demographic data, symptoms, endoscopic findings, EUS, and PET scan findings were obtained.

Results: Four hundred and twenty-six patients met the study criteria, of which 86 (20.2%) patients had limited stage EAC and 340 (79.8%) had locally advanced disease. The mean age was 65.4±10.3 years of which 356 (83.6%) were men and 393 (92.3%) were White. On multivariable analysis, age (above 75 or below 65 y), dysphagia [odds ratio (OR): 2.84], weight loss (OR: 2.06), protruding tumor (OR: 2.99), and tumor size >2 cm (OR: 3.3) were predictive of locally advanced disease, while gastrointestinal bleeding (OR: 0.36) and presence of visible Barrett's esophagus (OR: 0.4) were more likely to be associated with limited stage. A nomogram for predicting the risk of locally advanced EAC was constructed and internally validated.

Conclusions: We constructed a nomogram to facilitate an individualized prediction of the risk of locally advanced EAC. This model can aid in decision making for neoadjuvant therapy in EAC.
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http://dx.doi.org/10.1097/MCG.0000000000001489DOI Listing
January 2021

Short- and long-term surgical outcomes of total pancreatectomy with islet autotransplantation: A comparative analysis of surgical technique and intraoperative heparin dosing to optimize outcomes.

Pancreatology 2021 Jan 28;21(1):291-298. Epub 2020 Nov 28.

Department of General Surgery, Digestive Disease and Surgery Institute, Cleveland Clinic, Cleveland, OH, USA. Electronic address:

Background: Total pancreatectomy with islet autotransplantation (TP-IAT) is an uncommon surgical procedure with unique perioperative management. We evaluated the short- and long-term morbidity and mortality of TP-IAT to optimize surgical technique and heparin dosing during islet autotransplantation.

Methods: Eighty patients with chronic pancreatitis undergoing TP-IAT were reviewed. Primary outcome was to evaluate morbidity and mortality based on operative technique: classic (resection of antrum) vs pylorus-preserving. Secondary outcome was to evaluate the effect of heparin dosing (<60 vs ≥ 60 units/kg) during islet autotransplantation on postoperative hemorrhage and portal vein thrombosis (PVT) rates.

Results: There was no 90-day mortality, and median length of stay was 9 days. All patients underwent an open operation with 53 (66%) pylorus-preserving resections. The 30-day morbidity rate was 39%, with no difference between operative technique (p = 0.82). The median dose was different for each heparin group (<60: 52 units/kg vs ≥ 60: 66 units/kg, p < 0.0001). No difference was observed in postoperative hemorrhage rates between heparin groups (<60: 9% vs ≥ 60: 9%, p = 0.97), with no known incidence of PVT. Median follow-up was 36 months (IQR, 14-71). Morbidity >30 days after TP-IAT was 43% with a higher rate in the pylorus-preserving group (55% vs 15%, p < 0.0001), mainly attributed to marginal ulcer formation (15% vs 0%, p = 0.03).

Conclusions: A classic TP-IAT technique should be universally adopted to achieve optimal outcomes, particularly to prevent the formation of marginal ulcers. When considering PVT versus postoperative hemorrhage risk, a lower heparin dose nearing 50 units/kg is optimal. These findings highlight potential areas for future improvement.
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http://dx.doi.org/10.1016/j.pan.2020.11.013DOI Listing
January 2021

Survival impact based on hepatic artery lymph node status in pancreatic adenocarcinoma: A study of patients receiving modern chemotherapy.

J Surg Oncol 2021 Feb 6;123(2):399-406. Epub 2020 Nov 6.

Department of General Surgery, Cleveland Clinic Foundation, Cleveland, Ohio, USA.

Background: Chemotherapy for pancreatic adenocarcinoma (PDAC) has significantly improved in recent years. While the involvement of the hepatic artery lymph node (HALN; station 8a lymph node) likely represents advanced disease, a comparison to patients with metastases on modern chemotherapy is lacking.

Methods: Patients who underwent pancreatoduodenectomy with HALN sent for pathologic review at a single institution from 2003 to 2018 were reviewed. Patients who presented with liver-only metastases at the time of PDAC diagnosis (Stage IV) and received chemotherapy were identified. Multivariate Cox proportional hazards regression modeling was utilized and overall survival (OS) was estimated using Kaplan-Meier analysis.

Results: Of the 112 patients with a HALN sent for analysis, 17 (15%) were positive and 13 (76%) received chemotherapy. Ninety-four stage IV patients were identified and were significantly more likely to have received a multiagent rather than single-agent chemotherapy regimen compared to HALN positive patients (79.8% vs. 38.5%, p < .001). Median OS was significantly longer in all patients who underwent surgical resection, regardless of HALN status, compared to stage IV patients.

Conclusions: Patients undergoing pancreatoduodenectomy with HALN positivity have significantly improved OS compared to patients with stage IV disease. HALN involvement does not significantly alter survival among resected patients and does not warrant preoperative endoscopic ultrasound-guided biopsy.
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http://dx.doi.org/10.1002/jso.26281DOI Listing
February 2021

Application of optical character recognition with natural language processing for large-scale quality metric data extraction in colonoscopy reports.

Gastrointest Endosc 2021 03 3;93(3):750-757. Epub 2020 Sep 3.

Digestive Disease Institute, Cleveland Clinic, Cleveland, Ohio, USA.

Background And Aims: Colonoscopy is commonly performed for colorectal cancer screening in the United States. Reports are often generated in a non-standardized format and are not always integrated into electronic health records. Thus, this information is not readily available for streamlining quality management, participating in endoscopy registries, or reporting of patient- and center-specific risk factors predictive of outcomes. We aim to demonstrate the use of a new hybrid approach using natural language processing of charts that have been elucidated with optical character recognition processing (OCR/NLP hybrid) to obtain relevant clinical information from scanned colonoscopy and pathology reports, a technology co-developed by Cleveland Clinic and eHealth Technologies (West Henrietta, NY, USA).

Methods: This was a retrospective study conducted at Cleveland Clinic, Cleveland, Ohio, and the University of Minnesota, Minneapolis, Minnesota. A randomly sampled list of outpatient screening colonoscopy procedures and pathology reports was selected. Desired variables were then collected. Two researchers first manually reviewed the reports for the desired variables. Then, the OCR/NLP algorithm was used to obtain the same variables from 3 electronic health records in use at our institution: Epic (Verona, Wisc, USA), ProVation (Minneapolis, Minn, USA) used for endoscopy reporting, and Sunquest PowerPath (Tucson, Ariz, USA) used for pathology reporting.

Results: Compared with manual data extraction, the accuracy of the hybrid OCR/NLP approach to detect polyps was 95.8%, adenomas 98.5%, sessile serrated polyps 99.3%, advanced adenomas 98%, inadequate bowel preparation 98.4%, and failed cecal intubation 99%. Comparison of the dataset collected via NLP alone with that collected using the hybrid OCR/NLP approach showed that the accuracy for almost all variables was >99%.

Conclusions: Our study is the first to validate the use of a unique hybrid OCR/NLP technology to extract desired variables from scanned procedure and pathology reports contained in image format with an accuracy >95%.
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http://dx.doi.org/10.1016/j.gie.2020.08.038DOI Listing
March 2021

Comparative Effectiveness of Commercial Bowel Preparations in Ambulatory Patients Presenting for Screening or Surveillance Colonoscopy.

Dig Dis Sci 2021 Jun 20;66(6):2059-2068. Epub 2020 Jul 20.

Department of Internal Medicine, Medicine Institute, Cleveland Clinic, Cleveland, OH, USA.

Background: Inadequate bowel preparation (IBP) is associated with reduced adenoma detection. However, limited research has examined the impact of different commercial bowel preparations (CBPs) on IBP and adenoma detection. We aim to determine whether type of CBP used is associated with IBP or adenoma detection.

Methods: We retrospectively evaluated outpatient, screening or surveillance colonoscopies performed in the Cleveland Clinic health system between January 2011 and June 2017. IBP was defined by the Aronchick scale. Multilevel mixed-effects logistic regression was performed to assess the association between CBP type and IBP and adenoma detection. Fixed effects were defined as demographics, comorbidities, medication use, and colonoscopy factors. Random effect of individual endoscopist was considered.

Results: Of 153,639 colonoscopies, 75,874 records met inclusion criteria. Median age was 54; 50% were female; 17.7% had IBP, and adenoma detection rate was 32.6%. In adjusted analyses, compared to GoLYTELY, only NuLYTELY [OR 0.66 (95% CI 0.60, 0.72)] and SuPREP [OR 0.53 (95% CI 0.40, 0.69)] were associated with reduced IBP. Adenoma detection did not vary based on the type of bowel preparation used.

Conclusions: Among patients referred for screening or surveillance colonoscopy, choice of CBP was not associated with adenoma detection. Decisions about CBP should be based on other factors, such as tolerability, cost, or safety.
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http://dx.doi.org/10.1007/s10620-020-06492-zDOI Listing
June 2021

Dysplastic Progression to Adenocarcinoma is Equivalent in Ulcerative Colitis and Crohn's Disease.

J Crohns Colitis 2021 Jan;15(1):24-34

Department of Colorectal Surgery, Digestive Disease Surgical Institute, Cleveland Clinic, Cleveland, OH, USA.

Background: We sought to determine the rate of progression from dysplasia to adenocarcinoma in ulcerative colitis [UC] vs Crohn's diseases [CD] and describe the risk factors unique to each.

Methods: All adult patients [≥18 years] with a known diagnosis of either UC or CD who underwent a surveillance colonoscopy between January 1, 2010 and January 1, 2020 were included.

Results: A total of 23 751 surveillance colonoscopies were performed among 12 289 patients between January 1, 2010 and January 1, 2020; 6909 [56.2%] had a diagnosis of CD and 5380 [43.8%] had a diagnosis of UC. There were a total of 668 patients [5.4%] with low-grade dysplasia [LGD], 76 patients [0.62%] with high-grade dysplasia [HGD], and 68 patients [0.55%] with adenocarcinoma in the series; the majority of the dysplastic events were located in the right colon. Significantly more UC patients had a dysplastic event, but the rate of LGD and HGD dysplasia progression to adenocarcinoma was not significantly different in CD or UC [p = 0.682 and p = 1.0, respectively]. There was no significant difference in the rate of progression from LGD/HGD to adenocarcinoma based on random biopsies vs targeted biopsies of visible lesions [p = 0.37]. However, the rate of progression from LGD vs HGD to adenocarcinoma was significantly greater for HGD [p < 0.001].

Conclusion: While more UC patients were found to have neoplasia on colonoscopy, the rate of progression from LGD and HGD to adenocarcinoma was equivalent in UC and CD, suggesting that endoscopic surveillance strategies can remain consistent for all IBD patients.
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http://dx.doi.org/10.1093/ecco-jcc/jjaa133DOI Listing
January 2021

Pyloroplasty and the risk of Barrett's esophagus in patients with gastroparesis.

Dis Esophagus 2020 Nov;33(11)

Center of Excellence for Barrett's Esophagus, Department of Gastroenterology and Hepatology, Cleveland Clinic, Cleveland, OH, USA.

Barrett's esophagus (BE), a consequence of gastroesophageal reflux disease (GERD), is a premalignant condition for esophageal adenocarcinoma. Impaired gastric emptying leads to increased gastric volume and therefore more severe reflux. We seek to investigate the association between gastroparesis and BE and the predictors of BE among patients with gastroparesis. This is a retrospective review of patients seen at Cleveland Clinic between 2011 and 2016 who had an upper endoscopy and a gastric emptying study. Demographics, symptoms, medications, endoscopic and histological findings, and therapeutic interventions were abstracted. Risk of BE among gastroparesis group and control group was assessed, and logistic regression analysis was performed to identify predictors of BE among gastroparesis patients. Of the 4,154 patients, 864 (20.8%) had gastroparesis and 3, 290 (79.2%) had normal gastric emptying. The mean age was 51.4 ± 16.4 years, 72% were women and 80% were Caucasians. Among the gastroparesis group, 18 (2.1%) patients had BE compared to 71 (2.2%) cases of BE in the control group, P = 0.89. There were no differences in gender, race, reflux symptoms, or esophageal findings between the two groups. Among gastroparesis group, predictors of developing BE were a history of alcohol use (odds ratio [OR] 6.76; 95% confidence intervals [CI]: 1.65-27.67, P = 0.008), history of pyloroplasty (OR: 8.228; CI: 2.114-32.016, P = 0.002), and hiatal hernia (OR: 8.014; CI: 2.053-31.277, P = 0.003). Though gastroparesis is a known contributing factor for GERD, there was no increased prevalence of BE in gastroparesis. Among patients with gastroparesis, predictors of BE are history of alcohol use, hiatal hernia, and pyloroplasty.
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http://dx.doi.org/10.1093/dote/doaa049DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7672201PMC
November 2020

≥3 Nonadvanced Adenomas are More Common in the Era of Contemporary Colonoscopy and Not Associated With Metachronous Advanced Neoplasia.

J Clin Gastroenterol 2021 Apr;55(4):343-349

Departments of Gastroenterology, Hepatology and Nutrition.

Introduction: Data from standard definition colonoscopy era demonstrate patients with an advanced adenoma (≥10 mm, villous features or high-grade dysplasia) or ≥3 nonadvanced adenomas are considered high-risk for metachronous advanced neoplasia (MAN). Low-risk adenoma (LRA) patients are those with 1 to 2, <10 mm tubular adenomas. High definition colonoscopy, split-dose bowel preparation, and attention to adenoma detection enhance diminutive adenoma detection. We compared baseline adenoma characteristics between patients undergoing colonoscopy in a historic cohort (HC) and contemporary cohort (CC) to determine if number of patients with ≥3 nonadvanced adenomas are increased in CC, and if those features are associated with MAN in CC.

Materials And Methods: Patients undergoing their first colonoscopy in HC (<2006) and CC (≥2006) at age 50 and above were identified through natural language processing. Multivariable regression analysis compared baseline adenoma characteristics between HC and CC, and determined the association between baseline characteristics and MAN in CC patients.

Results: In total, 255,074 colonoscopies were performed between 1990 and 2015. A total of 9773 colonoscopies performed in the HC and 59,531 in the CC were included. At baseline, CC patients were more likely to have ≥3 nonadvanced adenomas [odds ratio (OR): 2.1, 95% confidence interval (CI): 1.7-2.6]. In 3,377 CC patients undergoing follow-up colonoscopy, the risk of MAN did not differ between patients with LRA versus those with ≥3 nonadvanced adenomas (6.3% vs. 4.6%, OR: 1.4, CI: 0.58-3.5) including 3-4 (6.1%, OR: 1.4, CI: 0.52-3.6) and ≥5 (7.7%, OR: 1.8, CI: 0.23-14.6), although few patients had ≥5 nonadvanced adenomas.

Conclusions: Colonoscopy in the contemporary era increases detection of patients with ≥3 nonadvanced adenomas, which do not increase the risk of MAN compared with LRA patients. A similar surveillance to LRA patients should be considered for those patients.
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http://dx.doi.org/10.1097/MCG.0000000000001364DOI Listing
April 2021

A natural language-based tool for diagnosis of serrated polyposis syndrome.

Gastrointest Endosc 2020 Oct 15;92(4):886-890. Epub 2020 May 15.

Department of Gastroenterology and Hepatology, Cleveland Clinic, Cleveland, Ohio, USA.

Background And Aims: Serrated polyposis syndrome (SPS) is common but under-recognized and is associated with an increased risk of colorectal cancer. The diagnosis is based on the World Health Organization (WHO) criteria and is inclusive of the cumulative number of lifetime serrated polyps. We used natural language processing (NLP) to extract colonoscopy and pathology data from the electronic medical record (EMR). The aim of this study was to assess feasibility of using an NLP-based SPS tool to identify patients with SPS.

Methods: NLP was used to extract data from 323,494 colonoscopies performed in 255,074 distinct patients between August 1998 and March 2016 to identify individuals who met SPS criteria. The accuracy of diagnosis of SPS was assessed by manual review of the EMR.

Results: Of 255,074 patients, 71 were identified as meeting 1 WHO criteria for SPS. Manual review confirmed the diagnosis of SPS to be accurate in 66 cases (93%). Erroneous diagnosis in the remaining 5 cases occurred because of duplicate polyp data by NLP extraction. Only 25 of 66 patients (38%) were diagnosed with SPS by a clinician in the EMR. Of these, SPS was diagnosed by NLP at least 2 years before the clinician in 5 of 25 patients (20%).

Conclusions: In a large cohort, NLP accurately identified SPS in over 90% of cases, most of which were not previously recognized. NLP can assist in collating colonoscopy and pathology data across multiple procedures in the same patient to make an accurate and earlier diagnosis of SPS.
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http://dx.doi.org/10.1016/j.gie.2020.04.077DOI Listing
October 2020

Can Unconventional Immunomodulatory Agents Help Alleviate COVID-19 Symptoms and Severity?

mSphere 2020 05 13;5(3). Epub 2020 May 13.

The Institute for Therapeutic Discovery, Delanson, New York, USA

Severe acute respiratory syndrome coronavirus 2 (SARS coronavirus 2, or SARS-CoV-2) is the cause of the respiratory infection known as COVID-19. From an immunopathological standpoint, coronaviruses such as SARS-CoV-2 induce increased levels of a variety of T-helper 1 (Th1) and inflammatory cytokines and chemokines, including interleukin-1 (IL-1), IL-6, CCL2 protein, and CXCL10 protein. In the absence of proven antiviral agents or an effective vaccine, substances with immunomodulatory activity may be able to inhibit inflammatory and Th1 cytokines and/or yield an anti-inflammatory and/or Th2 immune response to counteract COVID-19 symptoms and severity. This report briefly describes the following four unconventional but commercially accessible immunomodulatory agents that can be employed in clinical trials to evaluate their effectiveness at alleviating disease symptoms and severity: low-dose oral interferon alpha, microdose DNA, low-dose thimerosal, and phytocannabinoids.
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http://dx.doi.org/10.1128/mSphere.00288-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7227768PMC
May 2020

Effects Induced In Vivo by Exposure to Magnetic Signals Derived From a Healing Technique.

Dose Response 2020 Jan-Mar;18(1):1559325820907741. Epub 2020 Mar 30.

Beech Tree Labs, Inc, Providence, RI, USA.

Energy healing is a therapy said to manipulate and balance the flow of "energies" in the body. One such technique, the Bengston Healing Method (BHM), has shown some success in healing malignant tumors in animals and humans, but the mechanism of action and factors influencing therapeutic success of this method are poorly understood. In this study, we tested in vivo the antitumor potential of magnetic signals recorded during BHM healing. Balb/c mice engrafted with 4T1 breast cancer cells were exposed to this recording for 4 h/d on a weekly or daily basis for 28 days; control mice were not exposed at all. Tumors showed a trend to grow slower in the treatment versus control group during the fourth week of treatment. Elevated leukocyte counts, associated with an increase in blood levels of granulocyte-macrophage colony stimulating factor and interleukin-6, were observed in tumor-bearing mice exposed to the BHM recording but not in healthy animals exposed to the recording. This suggests that exposure to a recording of BHM may induce a biological response in tumor-bearing mice, but limited effects on tumor growth when observed within the predefined end point of 28 days. Studies involving longer end points are recommended to observe the progression of tumor growth.
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http://dx.doi.org/10.1177/1559325820907741DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7119239PMC
March 2020

Development of an Automated Algorithm to Generate Guideline-based Recommendations for Follow-up Colonoscopy.

Clin Gastroenterol Hepatol 2020 08 14;18(9):2038-2045.e1. Epub 2019 Oct 14.

Department of Gastroenterology, Hepatology and Nutrition, Cleveland Clinic, Cleveland, Ohio. Electronic address:

Background And Aims: Physician adherence to published colonoscopy surveillance guidelines varies. We aimed to develop and validate an automated clinical decision support algorithm that can extract procedure and pathology data from the electronic medical record (EMR) and generate surveillance intervals congruent with guidelines, which might increase physician adherence.

Methods: We constructed a clinical decision support (CDS) algorithm based on guidelines from the United States Multi-Society Task Force on Colorectal Cancer. We used a randomly generated validation dataset of 300 outpatient colonoscopies performed at the Cleveland Clinic from 2012 through 2016 to evaluate the accuracy of extracting data from reports stored in the EMR using natural language processing (NLP). We compared colonoscopy follow-up recommendations from the CDS algorithm, endoscopists, and task force guidelines. Using a testing dataset of 2439 colonoscopies, we compared endoscopist recommendations with those of the algorithm.

Results: Manual review of the validation dataset confirmed the NLP program accurately extracted procedure and pathology data for all cases. Recommendations made by endoscopists and the CDS algorithm were guideline-concordant in 62% and 99% of cases, respectively. Discrepant recommendations by endoscopists were earlier than recommended in 94% of the cases. In the testing dataset, 69% of endoscopist and NLP-CDS algorithm recommendations were concordant. Discrepant recommendations by endoscopists were earlier than guidelines in 91% of cases.

Conclusions: We constructed and tested an automated CDS algorithm that can use NLP-extracted data from the EMR to generate follow-up colonoscopy surveillance recommendations based on published guidelines.
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http://dx.doi.org/10.1016/j.cgh.2019.10.013DOI Listing
August 2020

Association of Adenoma and Proximal Sessile Serrated Polyp Detection Rates With Endoscopist Characteristics.

JAMA Surg 2019 07;154(7):627-635

Department of Gastroenterology and Hepatology, Cleveland Clinic, Cleveland, Ohio.

Importance: Research demonstrates adenoma detection rate (ADR) and proximal sessile serrated polyp detection rate (pSSPDR) are associated with endoscopist characteristics including sex, specialty, and years in practice. However, many studies have not adjusted for other risk factors associated with colonic neoplasia.

Objective: To assess the association between endoscopist characteristics and polyp detection after adjusting the factors included in previous studies as well as other factors.

Design, Setting, And Participants: This cohort study was conducted in the Cleveland Clinic health system with data from individuals undergoing screening colonoscopies between January 2015 and June 2017. The study analyzed data using methods from previous studies that have demonstrated significant associations between endoscopist characteristics and ADR or pSSPDR. Multilevel mixed-effects logistic regression was performed to examine 7 endoscopist characteristics associated with ADRs and pSSPDRs after controlling for patient demographic, clinical, and colonoscopy-associated factors.

Exposures: Seven characteristics of endoscopists performing colonoscopy.

Main Outcomes And Measures: The ADR and pSSPDR, with a hypothesis created after data collection began.

Results: A total of 16 089 colonoscopies were performed in 16 089 patients by 56 clinicians. Of these, 8339 patients were male (51.8%), and the median (range) age of the cohort was 59 (52-66) years. Analyzing the data by the methods used in 4 previous studies yielded an association between endoscopist and polyp detection; surgeons (OR, 0.49 [95% CI, 0.28-0.83]) and nongastroenterologists (OR, 0.50 [95% CI 0.29-0.85]) had reduced odds of pSSPDR, which was similar to results in previous studies. In a multilevel mixed-effects logistic regression analysis, ADR was not significantly associated with any endoscopist characteristic, and pSSPDR was only associated with years in practice (odds ratio, 0.86 [95% CI, 0.83-0.89] per increment of 10 years; P < .001) and number of annual colonoscopies performed (odds ratio, 1.05 [95% CI, 1.01-1.09] per 50 colonoscopies/year; P = .02).

Conclusions And Relevance: The differences in ADRs that were associated with 7 of 7 endoscopist characteristics and differences in pSSPDRs that were associated with 5 of 7 endoscopist characteristics in previous studies may have been associated with residual confounding, because they were not replicated in this analysis. Therefore, these characteristics should not influence the choice of endoscopist for colorectal cancer screening. However, clinicians further from their training and those with lower colonoscopy volumes have lower adjusted pSSPDRs and may need additional training to help increase pSSPDRs.
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http://dx.doi.org/10.1001/jamasurg.2019.0564DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6583839PMC
July 2019

Modifiable Factors Associated with Quality of Bowel Preparation Among Hospitalized Patients Undergoing Colonoscopy.

J Hosp Med 2019 05;14(5):278-283

Center for Value-Based Care Research, Medicine Institute, Cleveland Clinic, Cleveland, Ohio.

Introduction: Inadequate bowel preparation (IBP) is a common problem in hospitalized patients; however, little is known about how to prevent IBP. In a large, multihospital system, we evaluated the association between modifiable factors and IBP rate.

Methods: We reviewed data from adult (≥18 years) inpatients undergoing colonoscopy between January 2011 and June 2017. Colonoscopies performed in the intensive care unit or lacking descriptions of bowel preparation quality were excluded. Multivariate logistic regression analysis was performed to identify factors associated with IBP. A counterfactual analysis was performed to assess the potential contribution of modifiable factors to IBP.

Results: Of 8,819 patients that were included (median age of 64 years; 50.5% female), 51% had IBP. Patients with IBP stayed in the hospital one day longer than those with adequate bowel preparation (P < .001). Modifiable factors associated with IBP include opiate use within three days of colonoscopy (OR, 1.31; 95% CI, 1.18, 1.45), colonoscopy performed after 12:00 pm (OR, 1.25; 95% CI, 1.1, 1.41), and solid diet the day before colonoscopy (OR, 1.37; 95% CI, 1.18, 1.59). In the counterfactual analysis, if all patients avoided these three conditions, adjusted IBP rates were reduced by 5.6%.

Conclusions: Among hospitalized patients undergoing colonoscopy, IBP rates are high and associated with an increased length of stay. Avoiding opiates before colonoscopy, performing colonoscopy before noon, and maintaining patients on a liquid diet or nil per os might significantly reduce IBP rates.
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http://dx.doi.org/10.12788/jhm.3173DOI Listing
May 2019

Patient-Initiated Colonoscopy Scheduling Effectively Increases Colorectal Cancer Screening Adherence.

Dig Dis Sci 2019 09 15;64(9):2497-2504. Epub 2019 Mar 15.

Department of Gastroenterology and Hepatology, Digestive Disease and Surgical Institute, The Cleveland Clinic, 9500 Euclid Avenue/A30, Cleveland, OH, 44195, USA.

Background And Aim: We identified patients without medical record evidence of up-to-date colorectal cancer (CRC) screening and sent an invitation letter to self-schedule a colonoscopy without requiring prior primary care or gastroenterologist consultation. The aim of the study was to evaluate the response rate to the letter and factors associated with colonoscopy completion.

Methods: A computer algorithm invited patients not up to date with CRC screening, with an INR < 1.5, and living within 300 miles of the Cleveland Clinic main campus through a letter. Patients scheduled a colonoscopy through a dedicated phone line without any prior physician consultation. Clinical, demographic, and socioeconomic variables were extracted from the EMR through natural language algorithms. We analyzed the percentage of patients who completed a colonoscopy within 6 months of sending the letter and factors associated with colonoscopy completion.

Results: A total of 145,717 letters were sent. 1451 patients were deceased and excluded from analysis. 3.8% (5442) of letter recipients completed a colonoscopy. The strongest factors associated with colonoscopy completion on multivariate analysis included family history of polyps (OR 3.1, 95% CI 2.3, 4.2) or CRC (OR 2.1, 95% CI 1.7, 2.5). Other factors included younger age, male gender, married status, closer distance to endoscopy center, number of visits in the year prior, statin use, and diabetes. There were no immediate procedural complications.

Conclusions: Patient-initiated colonoscopy in response to letter invitation for CRC screening is effective and safe with safeguards established a priori. Consultation with a gastroenterologist or primary care physician is not necessary prior to colonoscopy. To our knowledge, this is the first study to evaluate patient-initiated colonoscopy for CRC cancer screening.
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http://dx.doi.org/10.1007/s10620-019-05584-9DOI Listing
September 2019

Common bile duct dilation after bariatric surgery.

Surg Endosc 2019 08 23;33(8):2531-2538. Epub 2018 Oct 23.

Department of Gastroenterology and Hepatology, Digestive Disease and Surgery Institute, Cleveland Clinic Foundation, Cleveland, OH, USA.

Background: Biliary dilation suggests obstruction and prompts further work up. Our experience with endoscopic ultrasound and endoscopic retrograde cholangiopancreatography in the symptomatic post-bariatric surgery population revealed many patients with radiographically dilated bile ducts, but endoscopically normal studies. It is unclear if this finding is phenomenological or an effect of surgery. Additionally, it is unknown whether the type of bariatric surgery alters biliary pathophysiology. Thus, we studied whether a change occurs in biliary diameter following Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG).

Methods: A single-center retrospective study assessing biliary diameter before and after RYGB or SG based on radiographic imaging. All adult patients undergoing RYGB or SG from January 2010 to December 2013 who had imaging studies before and > 3 months after surgery were included. Those with known obstructive etiologies and those without post-operative imaging were excluded. Common bile duct (CBD) diameter was re-read by a radiologist at the same location in the CBD for pre- and post-operative imaging. Baseline clinical factors and cholecystectomy status were collected.

Results: 269 patients met inclusion criteria (193 RYGB;76 SG). Between the groups, there were no significant differences in pre-operative characteristics. Average time from surgery to repeat imaging was 24.1 months. After adjusting for pre-operative factors, subjects who underwent an RYGB had an increase in CBD diameter of 1.4 mm (95% CI 0.096, 0.18), which was greater than the change following SG 0.5 mm(95% CI - 0.007, 0.11). The magnitude of this change did not depend on prior cholecystectomy in the RYGB cohort. Within the SG group, for patients without a prior cholecystectomy, there was a significant increase in post-operative CBD diameter of 0.8 mm(95% CI 0.02, 0.14).

Conclusion: Bariatric surgery results in CBD dilation, with changes more pronounced after RYGB. Biliary dilation occurs irrespective of cholecystectomy status. Further work is necessary to determine the cause and clinical implications of this phenomenon.
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http://dx.doi.org/10.1007/s00464-018-6546-9DOI Listing
August 2019

Transcriptional Changes in Cancer Cells Induced by Exposure to a Healing Method.

Dose Response 2018 Jul-Sep;16(3):1559325818782843. Epub 2018 Jul 11.

Beech Tree Labs, Inc, Providence, RI, USA.

Energy healing, or healing with intent, is a complementary and alternative medicine therapy reported to be beneficial with a wide variety of conditions. We are developing a delivery technology for a method previously tested in mouse models with solid tumors (the Bengston method) independent of the presence of a healer. The goal of this study was to assess whether stored or recorded energy has an impact on breast cancer cells in vitro, using energy-charged cotton and electromagnetic recording of healers practicing the method. Expression of genes involved in cancer and inflammation pathways was measured by quantitative reverse transcription polymerase chain reaction (qRT-PCR). Treatment of cells using energy-charged cotton resulted in statistically significant changes <1.5-fold. In cells exposed to an electromagnetic recording, 37 genes of 167 tested showed a >1.5-fold change when compared to the control, and 68 genes showing statistically significant fold changes. Two genes, ATP citrate lyase () and interleukin 1β (), were consistently downregulated at 4 and 24 hours of exposure to the recording, respectively, in 3 independent experiments. Both and were also downregulated in cells exposed to a hands-on delivery of the method, suggesting these 2 genes as potential markers of the healing method.
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http://dx.doi.org/10.1177/1559325818782843DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6047252PMC
July 2018

Serotonin and Histamine Therapy Increases Tetanic Forces of Myoblasts, Reduces Muscle Injury, and Improves Grip Strength Performance of Dmd(mdx) Mice.

Dose Response 2015 Oct-Dec;13(4):1559325815616351. Epub 2015 Nov 11.

Beech Tree Labs, Inc, Providence, RI, USA.

Duchenne muscular dystrophy (DMD) is a recessive X-linked fatal disorder caused by a mutation in the dystrophin gene. Although several therapeutic approaches have been studied, none has led to substantial long-term effects in patients. The aim of this study was to test a serotonin and histamine (S&H) combination on human skeletal myoblasts and Dmd(mdx) mice for its effects on muscle strength and injury. Normal human bioartificial muscles (BAMs) were treated, and muscle tetanic forces and muscle injury tests were performed using the MyoForce Analysis System. Dmd(mdx) mice, the murine model of DMD, were administered serotonin, histamine, or S&H combination twice daily for 6 weeks, and functional performance tests were conducted once a week. The S&H combination treatment caused significant increases in tetanic forces at all time points and concentrations tested as compared to the saline controls. Dose response of the BAMs to the treatment demonstrated a significant increase in force generation at all concentrations compared to the controls after 3 to 4 days of drug treatment. The highest 3 concentrations had a significant effect on lowering contractile-induced injury as measured by a reduction in the release of adenylate kinase. Histamine-only and S&H treatments improved grip strength of Dmd(mdx) mice, whereas serotonin-only treatment resulted in no significant improvement in muscle strength. The results of this study indicate that S&H therapy might be a promising new strategy for muscular dystrophies and that the mechanism should be further investigated.
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http://dx.doi.org/10.1177/1559325815616351DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4679190PMC
January 2016

Percutaneous Endoscopic Gastrostomy for Decompression of Nonmalignant Gastrointestinal Disease.

J Laparoendosc Adv Surg Tech A 2015 Oct 22;25(10):804-7. Epub 2015 Sep 22.

1 Bariatric and Metabolic Institute , Cleveland Clinic, Cleveland, Ohio.

Introduction: The utility of percutaneous endoscopic gastrostomy (PEG) decompression for inoperable malignant bowel obstruction is well documented. However, there are limited data on decompressive PEG for prolonged ileus, gut dysmotility, and/or complicated nonmalignant bowel obstruction. The aim of this study was to assess the safety and short-term outcomes of decompressive PEG for nonmalignant indications.

Subjects And Methods: After Institutional Review Board approval, we retrospectively reviewed and analyzed all PEG insertions completed at our institution between 2009 and 2014 for prolonged ileus, gut dysmotility, or nonmalignant obstruction.

Results: We identified 72 patients (42 females, 30 males; mean age, 58.8 ± 15.2 years) who underwent decompressive PEG for nonmalignant indications. There were no procedural complications or mortalities. The mean pre- and postprocedural length of stays were 14.4 ± 10.7 and 7.6 ± 11.1 days, respectively (P = .0003). The 30-day re-admission rate was 12.5% (9 patients; the majority for unrelated issues). Fifty-two (72%) of the 72 patients were discharged with a PEG for decompression for a median of 69.5 (range, 17-316) days; the remaining 20 (28%) patients were lost to follow-up and were assumed to continue follow-up with their primary referring center. Of the 72 patients, 63 (87.5%) were discharged on total parenteral nutrition (TPN); 36 (50%) of those continued to receive TPN for a median of 51 (range, 4-316) days after discharge, and resolution of their mechanical obstruction was ultimately achieved, so that they subsequently resumed enteral nutrition. Twenty-four (33%) patients were lost to follow-up; because they were referred to our tertiary referral center, we assumed they continued follow-up at their referring institution. Three (4%) patients ultimately went on to use TPN indefinitely and thus were considered to be chronically TPN-dependent.

Conclusions: Decompressive PEG insertion is safe and effective at alleviating obstructive symptoms in patients with prolonged postoperative ileus, gut dysmotility, and/or complicated nonmalignant obstruction.
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http://dx.doi.org/10.1089/lap.2014.0619DOI Listing
October 2015

Combination histamine and serotonin treatment after simulated childbirth injury improves stress urinary incontinence.

Neurourol Urodyn 2016 08 17;35(6):703-10. Epub 2015 Jun 17.

Department of Biomedical Engineering, The Cleveland Clinic, Cleveland, Ohio.

Aims: Histamine and serotonin-related pharmaceuticals have the potential to modulate micturition and continence. The aim of this study was to determine if treatment with histamine and/or serotonin improves stress urinary incontinence (SUI) in female rats.

Methods: Twenty-six age-matched female rats underwent pudendal nerve crush and vaginal distension (PNC + VD), to produce SUI. One week after injury, rats were treated subcutaneously with saline, histamine (1.1 μg), serotonin (2μg), or the combination of both twice daily for another week. A sham injured group received sham PNC + VD and were treated with saline (n = 7). Leak point pressure (LPP) testing with simultaneous external urethral sphincter (EUS) electromyography (EMG) was conducted 2 weeks after injury. The urethra was harvested for qualitative and quantitative histology. Data were analyzed with a one-way ANOVA and Student-Newman-Keuls posthoc test with P < 0.05 indicating statistically significant differences between groups.

Results: Combination treatment significantly increased LPP after PNC + VD compared to injured sham treatment and treatment with either histamine or serotonin alone. Compared to injured sham treated rats, all three treatments significantly increased EUS EMG amplitude at both baseline and peak pressure and EUS EMG firing rate at peak pressure during LPP testing. There were more consistent urethral striated muscle fibers and thicker smooth and striated muscle with combination and histamine treatment. There was a statistically significant shift to a greater proportion of thicker collagen fibers in the urethra in serotonin and combination treated rats compared with injured sham treated rats.

Conclusions: Combination treatment was the most effective and may provide an effective therapy for SUI. Neurourol. Urodynam. 35:703-710, 2016. © 2015 Wiley Periodicals, Inc.
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http://dx.doi.org/10.1002/nau.22793DOI Listing
August 2016

Minimally invasive duodenojejunostomy for superior mesenteric artery syndrome: a case series and review of the literature.

Surg Endosc 2015 May 21;29(5):1137-44. Epub 2015 Feb 21.

Anesthesiology and Perioperative Medicine, Georgia Regents University, Augusta, GA, 30907, USA,

Background: Superior mesenteric artery syndrome (SMAS) is a disorder characterized by vascular compression of the duodenum leading to mechanical obstruction. Surgical intervention is indicated in patients who fail standard non-operative management, in which duodenojejunostomy is favored based on previous small series. Given the rarity of the condition, knowledge of the optimal indications for surgery, risk of postoperative complications, and prognosis of SMAS after minimally invasive duodenojejunostomy is limited.

Methods: A retrospective chart review was performed on patients who underwent minimally invasive duodenojejunostomy for SMAS from March 2005 to December 2013 at our "healthcare system". We analyzed patients' presentations, work-up, surgical therapy, and outcomes.

Results: A series of 14 patients with SMAS underwent minimally invasive duodenojejunostomy. All of these patients met clinical criteria of SMAS with radiological confirmation. Average weight loss before surgery was 10.7 kg. Depression and eating disorders were comorbid in 6/14 patients. The mean age was 39 years (19-91 years). Twelve operations were completed laparoscopically and two were performed with robotic assistance. Mean operation duration was 119 min and average length of hospital stay was 5.5 days. There were no immediate postoperative complications. One patient developed a delayed anastomotic stricture that improved with single endoscopic balloon dilation. Initial symptom improvement occurred in all patients and the improvement occurred in 11 patients (79%) during the follow-up. At a mean follow-up of 20 months, two patients experienced complications, including one infection at a simultaneously placed J-tube site and one patient with dumping syndrome. Mean weight gain was 3.8 kg (p < 0.01).

Conclusion: SMAS should be considered a potential diagnosis in patients who present with a history of persistent postprandial vomiting, epigastric pain, and weight loss and confirmatory radiographic findings. In well-selected patients, minimally invasive duodenojejunostomy is a safe and effective treatment for SMAS with excellent short-term outcomes.
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http://dx.doi.org/10.1007/s00464-014-3775-4DOI Listing
May 2015

Surgical treatment of medically refractory gastroparesis in the morbidly obese.

Surg Endosc 2015 Sep 17;29(9):2683-9. Epub 2015 Jan 17.

Digestive Disease Institute, Cleveland Clinic, Cleveland, OH, USA,

Introduction: Surgical management of medically refractory gastroparesis remains a challenge. Case series and small retrospective studies describe clinical benefits from surgical intervention; however, no study reports the efficacy of gastric electrical stimulation (GES) or Roux-en-Y gastrojejunostomy with or without near-total gastrectomy (RYGJ) in morbidly obese patients with severe gastroparesis.

Methods: A chart review was performed on all morbidly obese patients (BMI > 35 kg/m(2)) who underwent GES or RYGJ for medically refractory gastroparesis from March 2002 to December 2012 at the Cleveland Clinic. The main outcomes examined were symptom improvement, postoperative complications, and change in BMI.

Results: A total of 20 morbidly obese patients underwent GES placement. Seven morbidly obese patients had RYGJ with or without resection of the remnant stomach surgery. All operations were completed laparoscopically. In GES group, 18 patients had initial symptom improvement (90%) and 11 (55%) rated their symptom improved at the last follow-up. During the average 23 months' follow-up, 9 patients (45%) experienced at least one readmission for gastrointestinal reasons. Early complications included two infections at a simultaneously placed J-tube site and one seroma. In the RYGJ group, all patients, including 4 patients who failed GES and subsequently converted to RYGJ, experienced short-term symptom improvement and 5 patients (71%) rated their symptoms as improved at last follow-up. One duodenal stump leak happened in the RYGJ group. There were no 30-day mortalities in either group. The BMI change after GES implantation was 0.6 ± 4 kg/m(2) versus -7.7 ± 4 kg/m(2) after RYGJ (p < 0.01).

Conclusion: GES implantation and RYGJ are both effective in terms of symptom control for medically refractory gastroparesis in morbidly obese. Both options can be performed in a minimally invasive fashion with low morbidity. Patients who have no improvement of symptoms for refractory gastroparesis after GES implantation can be successfully converted laparoscopically to RYGJ.
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http://dx.doi.org/10.1007/s00464-014-3990-zDOI Listing
September 2015

Streptolysin-O/antibiotics adjunct therapy modulates site-specific expression of extracellular matrix and inflammatory genes in lungs of Rhodococcus equi infected foals.

Vet Res Commun 2013 Jun 9;37(2):145-54. Epub 2013 Mar 9.

Beech Tree Labs Inc, 117 Chapman St, Providence, RI 02905, USA.

The addition of streptolysin-O (SLO) to the standard antibiotics regimen was shown to be superior to antibiotics alone after experimental infection of foals with Rhodoccocus equi (R. equi). The objective of this study is to investigate this response by determining the site-specific expression of extracellular matrix (ECM) and inflammatory response genes in biopsy samples taken from three distinct lung regions of the infected foals. Twenty-four foals were challenged by intrabronchial instillation of R. equi and assigned to four treatment groups: SLO/antibiotics adjunct therapy, antibiotics-only therapy (7.5 mg/kg clarithromycin and 5 mg/kg rifampin), SLO-only, and saline-only treatments. Treatments were administered twice daily for 16 days unless symptoms progressed to the point where the foals needed to be euthanized. Gene expressions were determined using custom-designed equine real-time qPCR arrays containing forty-eight genes from ECM remodeling and inflammation pathways. A non-parametric Wilcoxon signed-rank test for independent samples was applied to two pairs of time-matched comparison groups, SLO/antibiotics vs. antibiotics-only and SLO-only vs. saline-only, to document the significant differences in gene expressions within these groups. Several genes, MMP9, MMP2, TIMP2, COL1A1, COL12A1, ITGAL, ITGB1, FN1, CCL2, CCL3, CXCL9, TNFα, SMAD7, CD40, IL10, TGFB1, and TLR2, were significantly regulated compared to the unchallenged/untreated control foals. The results of this study demonstrate that enhancement of clinical responses by SLO is consistent with the changes in expression of critical genes in ECM remodeling and inflammatory response pathways.
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http://dx.doi.org/10.1007/s11259-013-9557-yDOI Listing
June 2013

Long-term effects of alemtuzumab on regulatory and memory T-cell subsets in kidney transplantation.

Transplantation 2012 Apr;93(8):813-21

Human Immunology Program, Thomas E. Starzl Transplantation Institute and Department of Surgery, University of Pittsburgh, Pittsburgh, PA, USA.

Background: Induction with lymphocyte-depleting antibodies is routinely used to prevent rejection but often skews T cells toward memory. It is not fully understood which memory and regulatory T-cell subsets are most affected and how they relate to clinical outcomes.

Methods: We analyzed T cells from 57 living-donor renal transplant recipients (12 reactive and 45 quiescent) 2.8±1.4 years after alemtuzumab induction. Thirty-four healthy subjects and nine patients with acute cellular rejection (ACR) were also studied.

Results: We found that alemtuzumab caused protracted CD4 more than CD8 T-lymphocyte deficiency, increased proportion of CD4 memory T cells, and decreased proportion of CD4 regulatory T cells. Reactive patients exhibited higher proportions of CD4 effector memory T cells (TEM) and CD8 terminally differentiated TEM (TEMRA), with greater CD4 TEM and CD8 TEMRA to regulatory T cell ratios, than quiescent patients or healthy controls. Patients with ongoing ACR had profound reduction in circulating CD8 TEMRA. Mixed lymphocyte assays showed significantly lower T-cell proliferation to donor than third-party antigens in the quiescent group, while reactive and ACR patients exhibited increased effector molecules in CD8 T cells.

Conclusions: Our findings provide evidence that T-cell skewing toward TEM may be associated with antigraft reactivity long after lymphodepletion. Further testing of TEM and TEMRA subsets as rejection predictors is warranted.
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http://dx.doi.org/10.1097/TP.0b013e318247a717DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3323763PMC
April 2012

Effects of nerve growth factor (NGF), fluoxetine, and amitriptyline on gene expression profiles in rat brain.

Neuropeptides 2011 Oct 5;45(5):317-22. Epub 2011 Aug 5.

Providence Veterans Affairs Medical Center, Brown University, RI 02912, USA.

Evidence suggests that nerve growth factor (NGF) may have antidepressant properties but the pharmacological mechanisms remain unknown. Previously, we found that NGF improved performance in the forced swim test in Flinders Sensitive Line rats, but did not appear to have similar biochemical actions with the antidepressant fluoxetine. Gene expression profiles for neurotransmitter receptors and regulator-related genes in the amygdala/hippocampus were determined in rats treated for 14days with NGF, fluoxetine, amitriptyline, or saline. Gene expression was measured using an RT(2) profiler PCR Array System to determine the basis for this effect. Compared with saline, there were numerous genes with significantly altered mRNA levels in the amygdala/hippocampal region. Overlap was found between the mRNA levels of genes altered by NGF and the two antidepressant medications including genes related to the cholinergic and dopaminergic systems. However, decreased mRNA levels of Drd5, Sstr3, Htr3a, and Cckar genes in the amygdala/hippocampus were uniquely regulated by NGF. The results of this study are consistent with a previous conclusion that the antidepressant effects of NGF are mediated through non-traditional receptors for traditionally considered neurotransmitters and may suggest a particular utility of NGF in treating comorbid depression and addiction.
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http://dx.doi.org/10.1016/j.npep.2011.06.002DOI Listing
October 2011

The use of streptolysin O (SLO) as an adjunct therapy for Rhodococcus equi pneumonia in foals.

Vet Microbiol 2011 Dec 7;154(1-2):156-62. Epub 2011 Jul 7.

Maxwell H. Gluck Equine Research Center, Department of Veterinary Science, University of Kentucky, Lexington, KY, United States.

Rhodococcus equi is a soil borne bacterium that causes severe morbidity and death in young foals. The economic costs of the disease include loss of life, treatment expenses, veterinary monitoring expenses and, perhaps most importantly, potential reduction in future athletic performance in horses that suffer severe lung abscessations caused by R. equi. Current standard of care for pneumonia caused by R. equi is treatment with a macrolide antimicrobial and rifampicin. However, the hallmark of pneumonia caused by R. equi is severe formation of pyogranulomas and a walling off effect that can prevent systemic antibiotics from reaching antimicrobial concentrations in lung tissues. It is hypothesized that streptolysin O (SLO) used as an adjunct therapy with antibiotics will reduce the duration and severity of disease caused by R. equi pneumonia compared to antibiotic therapy alone. Addition of SLO to the antibiotic enhanced clinical responses compared to the other groups, including the antibiotic alone group. Of particular significance were lower bacterial counts in the lungs and longer survival time in those foals treated with SLO and antibiotics.
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http://dx.doi.org/10.1016/j.vetmic.2011.06.037DOI Listing
December 2011