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Disruption of CCR5 signaling to treat COVID-19-associated cytokine storm: Case series of four critically ill patients treated with leronlimab

Agresti, Nicholas; Lalezari, Jacob P; Amodeo, Phillip P; Mody, Kabir; Mosher, Steven F; Seethamraju, Harish; Kelly, Scott A; Pourhassan, Nader Z; Sudduth, C David; Bovinet, Christopher; ElSharkawi, Ahmed E; Patterson, Bruce K; Stephen, Reejis; Sacha, Jonah B; Wu, Helen L; Gross, Seth A; Dhody, Kush
Coronavirus disease 2019 (COVID-19) is associated with considerable morbidity and mortality. The number of confirmed cases of infection with SARS-CoV-2, the virus causing COVID-19 continues to escalate with over 70 million confirmed cases and over 1.6 million confirmed deaths. Severe-to-critical COVID-19 is associated with a dysregulated host immune response to the virus, which is thought to lead to pathogenic immune dysregulation and end-organ damage. Presently few effective treatment options are available to treat COVID-19. Leronlimab is a humanized IgG4, kappa monoclonal antibody that blocks C-C chemokine receptor type 5 (CCR5). It has been shown that in patients with severe COVID-19 treatment with leronlimab reduces elevated plasma IL-6 and chemokine ligand 5 (CCL5), and normalized CD4/CD8 ratios. We administered leronlimab to 4 critically ill COVID-19 patients in intensive care. All 4 of these patients improved clinically as measured by vasopressor support, and discontinuation of hemodialysis and mechanical ventilation. Following administration of leronlimab there was a statistically significant decrease in IL-6 observed in patient A (p=0.034) from day 0-7 and patient D (p=0.027) from day 0-14. This corresponds to restoration of the immune function as measured by CD4+/CD8+ T cell ratio. Although two of the patients went on to survive the other two subsequently died of surgical complications after an initial recovery from SARS-CoV-2 infection.
PMCID:7823045
PMID: 33521616
ISSN: 2589-9090
CID: 4771782

Use, Yield, and Risk of Device-assisted Enteroscopy in the United States: Results From a Large Retrospective Multicenter Cohort

Noujaim, Michael G; Parish, Alice; Raines, Daniel; Gross, Seth A; Cave, David; Vance, Iris; Beyer, David; Liu, Diana; Hoffman, Benjamin; Lawrence, Zoe; Castillo, Gabriel; Pavri, Tanya; Niedzwiecki, Donna; Wild, Daniel
INTRODUCTION/BACKGROUND:Since 2001, device-assisted enteroscopy (DAE) has revolutionized the diagnostic and therapeutic capabilities for managing small bowel pathology. Though commonly performed, there have been no recent large studies to assess the use, yield, and risks of DAE and none that include all 3 DAE modalities. We hypothesized that DAE is safe with high diagnostic and therapeutic yields achieved within reasonable procedure duration and here we present a large retrospective multicenter US study evaluating the use, yield, and complications of DAE. METHODS:After obtaining institutional review board approval, electronic records were used to identify all DAE's performed for luminal small bowel evaluation in adult patients at 4 US referral centers (Duke University Medical Center, New York University Langone Medical Center, Louisiana State University Health Sciences Center, and University of Massachusetts Medical Center) from January 1, 2014 to January 1, 2019. Electronic medical records were reviewed to collect and analyze a variety of procedure-related outcomes. Using the data pooled across centers, descriptive statistics were generated for the patient and procedure-related characteristics and outcomes; relationships between characteristics and outcomes were explored. RESULTS:A total of 1787 DAE's were performed over this 5-year period (392 at Duke University Medical Center, 887 at Louisiana State University Health Sciences Center, 312 at New York University Langone Medical Center, and 195 at University of Massachusetts Medical Center). Of these, there were 1017 (57%) double-balloon, 391 (29%) single-balloon, and 378 (21%) spiral enteroscopies. The mean age of patients undergoing DAE was 66 years and 53% of examinations were performed on women; 18% of patients in the cohort underwent >1 DAE over this time span. A total of 53% of examinations were performed for suspected small bowel bleeding, 31% were directly guided by video capsule endoscopy findings and 8% were performed for abnormal imaging. A total of 85% of examinations used an antegrade approach and DAE took a mean of 45 minutes to complete; 76% of examinations revealed abnormal findings, with vascular, inflammatory, and neoplastic findings seen in 49%, 17%, and 15% of the cohort, respectively. Older age was significantly associated with any abnormal finding, including arteriovenous malformations (P<0.0001); 50% of examinations included a therapeutic maneuver, most commonly argon plasma coagulation/cautery (43%). There were complications in 16 examinations (0.9%) including 2 perforations (0.1%), 6 cases with bleeding (0.3%) and 1 episode of pancreatitis (0.1%). CONCLUSIONS:DAE is most commonly performed to evaluate suspected small bowel bleeding and is commonly directed by video capsule findings. DAE is safe, has a high diagnostic yield, with 76% of examinations showing abnormal findings, and frequently features therapeutic maneuvers. Advancing age is associated with abnormal findings on DAE.
PMID: 32947375
ISSN: 1539-2031
CID: 4636562

THE USE OF DEVICE-ASSISTED ENTEROSCOPY IN DIAGNOSING AND TREATING SMALL BOWEL DISORDERS, RESULTS FROM A LARGE RETROSPECTIVE MUTLI-CENTER US STUDY [Meeting Abstract]

Wild, Daniel; Noujaim, Michael G.; Vance, Iris; Parish, Alice; Raines, Daniel; Gross, Seth A.; Beyer, David; Liu, Diana; Hoffman, Benjamin; Lawrence, Zoe; Castillo, Gabriel; Pavri, Tanya; Niedzwiecki, Donna; Cave, David R.
ISI:000545678401355
ISSN: 0016-5107
CID: 4848702

Colonic intussusception: It's not malignant [Meeting Abstract]

Gross, S; Pochapin, M
INTRODUCTION: Lipomas are benign submosal lesions, which can be found throughout the gastrointestinal tract. In most patients, these are incidentals findings and patients are asymptomatic. However, there are instances when lipomas can cause symptoms of obstruction if very large. This case highlights a rare complication of a colonic lipoma. CASE DESCRIPTION/METHODS: The case is of a 31-year-old man, who initially presented for intermittent rectal bleeding. On initial evaluation he had a benign abdominal exam, but a rectal exam was performed suggested hemorrhoids. There was no significant past medical history and no family history of colon cancer. A colonoscopy was performed demonstrating sigmoid diverticulosis, an ascending colon lipoma, and internal hemorrhoids, the likely cause of bleeding. Ten days later the patient calls with intermittent abdominal pain for the last several days. On further questioning, the patient does report occasional episodes of a similar sharp pain for the last few years, but in the last few days the pain has intensified. An outpatient CT scan was performed showing a 6.8 cm lipoma in the transverse colon causing colo-colonic intussusception (image 1). The patient was taken for urgent robotic right hemicolectomy with a side to side ileocolic anastomosis. Final pathology confirmed a large lipoma. The patient fully recovered and symptoms have resolved.
Discussion(s): DISCUSSION: Intussusception is when the bowel telescopes on itself. The most common location is the small bowel, but intussusception can occur in the colon 1. A lipoma is a benign submucosal tumor, which can be found in the colon. In the majority of cases lipomas are incidental finding and cause no symptoms. Based on autopsy reports, the incidence rate of colonic lipomas is 0.2-0.8%. However, clinical symptoms might include abdominal pain, bleeding, and perforation. Clinicians should be aware of this unique presentation, which requires surgical intervention
EMBASE:633660030
ISSN: 1572-0241
CID: 4720422

Telehealth in the time of COVID-19: Gastroenterologists' use and attitudes [Meeting Abstract]

Snell, D B; Wallace, T; Pochapin, M B; Gross, S A; Brodsky, T
INTRODUCTION: Telehealth involves the use of electronic information and telecommunications to promote healthcare. Physician experience is critical in assessing the impact of telehealth on clinical outcomes and utilization. Gastroenterologists' use and attitudes towards telehealth are largely unknown. We aimed to identify gastroenterologists' professional attitudes towards their use of telehealth and its effect on patient care during the COVID-19 pandemic.
METHOD(S): We performed a cross sectional survey of outpatient gastroenterologists and hepatologists at a single tertiary academic medical center in June 2020. Clinicians were invited to participate in an electronic survey. Survey questions involved either single or multiple categorical responses.
RESULT(S): A total of 46 respondents (51 +/- 14 years old) participated, 70% of which were male. 44 (96%) respondents had no telehealth experience prior to the pandemic. Clinicians conducted 19 +/- 13 visits weekly with a mean length of 24 +/- 9 minutes. 88% of providers reported telehealth allowed for increased flexibility, both in patient scheduling and their personal lives. Telehealth was always or usually effective in addressing patients' clinical needs 91% of the time. 29 (63%) respondents estimated that 10% or fewer patients required in-person follow-up. Clinicians estimated 93% of patients desired the continued option of telehealth, and 42 (91%) providers wanted to continue telehealth in some capacity, conditional on reimbursement. Those interested would use telehealth for follow-up visits (28%), on a patient-by-patient basis (23%), or for new visits (20%). While 21 (46%) respondents felt that telehealth and in-person visits required equal effort, 16 (35%) felt telehealth required more effort. Reasons cited for telehealth requiring more effort included coordination of care (30%), technical difficulty for the patient (20%), and more charting (17%).
CONCLUSION(S): While most clinicians had no telehealth experience before the pandemic, a majority were interested in using telehealth in the future, citing increased flexibility for both provider and patient. Physicians felt that telehealth was effective in addressing patients' needs. However, many felt that telehealth required more effort, particularly in regard to coordination of care and technical difficulties. Newer telehealth platforms should address connectivity issues. Future studies should focus on patients' attitudes towards telehealth, and the effect of telehealth on healthcare outcomes, utilization and costs
EMBASE:633658697
ISSN: 1572-0241
CID: 4720482

Robotic-Assisted Endoscopic Submucosal Dissection of Distal Colon and Rectal Lesions [Meeting Abstract]

Cui, Y; Hartz, K M; Bernstein, M; Obias, V; Mathew, A; Bardakcioglu, O; Horner, L; Shah, P; Kim, S; Haber, G; Gross, S A
INTRODUCTION: Endoscopic submucosal dissection (ESD) and endoscopic full-thickness resection (EFTR) are therapeutic alternatives to surgery for resection of colon and rectal lesions. In regards to large colon and rectal polyps and tumors, both ESD and EFTR have high en bloc resection rates and low recurrence rates, but are limited by training, procedure length, stability, and instrumentation. The Robotic System (RS) is a new robot-assisted endoscopic platform with multiple degrees of freedom allowing improved visualization, dexterity, and tissue manipulation with traction. This is the first U.S. experience assessing the feasibility and safety of robot-assisted ESD and EFTR in resection of distal colon and rectal lesions and its implication for polyps and tumors.
METHOD(S): This is a multicenter retrospective study from five institutions. Patients with distal colon or rectal lesions who underwent either ESD or EFTR with the RS were included. Each patient's clinical history, endoscopic findings, procedural records, and pathology records were reviewed.
RESULT(S): Forty-one patients underwent either ESD or EFTR with the RS for distal colon or rectal lesions, with an average total resection time of 135.0 minutes (s 62.8, n = 24). On average, lesions were 9.3 cm from the anal verge (range: 2 cm to 17 cm, n = 35) and were 30.0 mm in max diameter (range: 9 to 77 mm, n = 28). There were 13 (31.7%) neoplasms and 23 (56.1%) adenomatous polyps; other lesions included inflammatory polyps, diffuse nodular lymphoid hyperplasia, and granulation tissue-all were suspicious for malignancy. Neoplasms included 11 adenocarcinomas and 2 GISTs. Adenomatous polyps included 11 tubular adenomas and 11 tubulovillous adenomas. Twenty-nine out of 34 patients (85.3%) with either adenomatous polyps or adenocarcinoma were successfully removed with the RS alone. Of these, 23 (79.3%) demonstrated clean margins on pathology. Post-endoscopic complications included rectal pain and bleeding.
CONCLUSION(S): This report demonstrates a role of robotic endoscopy for the safe and effective treatment of natural orifice endoscopic surgical resection, with its benefits including traction and triangulation. As endoscopic surgery in the form of ESD evolves, refinement of the tools and techniques of the robotic platform will allow endoscopists to have shorter learning curves and resection of distal colon and rectal polyps and tumors to have higher negative margin rates, potentially allowing more endoscopists the ability to perform ESD
EMBASE:633657215
ISSN: 1572-0241
CID: 4720562

Prep-Free Screening Capsule to Redefine Colorectal Cancer Screening and Prevention [Meeting Abstract]

Gross, S A; Rajan, E; Hansel, S; Rainis, T; Moshkovitz, M; Half, E; Gralnek, I; Shpak, B; AbuFrecha, N; Ringel, Y; Binyaminov, F; Arber, N
INTRODUCTION: Colorectal cancer (CRC) can be prevented by removal of polyps during colo-noscopy. Colonoscopy barriers include invasiveness and need of bowel cleansing preparation. Non-invasive CRC stool based tests may increase CRC screening adherence, but are not designed as a tool to identify pre-cancerous polyps. We present data from a novel prep-free colon cancer screening technology for the detection of pre-cancerous polyps.
METHOD(S): An ingestible capsule descends through the gastrointestinal tract via natural motility and scans the colon for structural abnormalities using an ultra-low-dose X-ray source. The data is transmitted to a recorder unit attached to the patient. The test requires no preparation or sedation, allowing patients to continue their daily routine. A 187 patients were performed in the U.S. and Israel designed to assess the safety and effectiveness of the technology in detecting polyps. All sites received EC/IRB approvals. Patients ingested the capsule with a contrast agent and underwent a colonoscopy performed by independent gastroenterologists, who were blinded to the test's results.
RESULT(S): Sensitivity of the capsule in detecting clinically significant polyps (>10 mm) was 76% and specificity was 82% with no severe or serious adverse events reported. Some patients reported mild abdominal pain and nausea. Patient characteristics are shown in Table 1. A survey questionnaire resulted with a score of 4.18 compared to a 2.91 for colonoscopy (P = 0.0011) using a scoring system of 1 (strongly disagree) to 5 (strongly agree) in response to the phrase: "I would recommend the test for colonic screening".
CONCLUSION(S): The reported patient satisfaction, sensitivity, specificity and safety highlights the potential of the capsule technology as a tool for CRC prevention. Further studies are needed to make this technology part of our routine colon cancer prevention armamentarium
EMBASE:633655965
ISSN: 1572-0241
CID: 4720652

Gastrointestinal endoscopy during the coronavirus pandemic in the New York area: results from a multi-institutional survey

Mahadev, Srihari; Aroniadis, Olga C; Barraza, Luis H; Agarunov, Emil; Smith, Michael S; Goodman, Adam J; Benias, Petros C; Buscaglia, Jonathan M; Gross, Seth A; Kasmin, Franklin; Cohen, Jonathan; Carr-Locke, David L; Greenwald, David; Mendelsohn, Robin; Sethi, Amrita; Gonda, Tamas A
Background and study aims  The coronavirus disease 2019 (COVID-19), and measures taken to mitigate its impact, have profoundly affected the clinical care of gastroenterology patients and the work of endoscopy units. We aimed to describe the clinical care delivered by gastroenterologists and the type of procedures performed during the early to peak period of the pandemic. Methods  Endoscopy leaders in the New York region were invited to participate in an electronic survey describing operations and clinical service. Surveys were distributed on April 7, 2020 and responses were collected over the following week. A follow-up survey was distributed on April 20, 2020. Participants were asked to report procedure volumes and patient characteristics, as well protocols for staffing and testing for COVID-19. Results  Eleven large academic endoscopy units in the New York City region responded to the survey, representing every major hospital system. COVID patients occupied an average of 54.5 % (18 - 84 %) of hospital beds at the time of survey completion, with 14.5 % (2 %-23 %) of COVID patients requiring intensive care. Endoscopy procedure volume and the number of physicians performing procedures declined by 90 % (66 %-98 %) and 84.5 % (50 %-97 %) respectively following introduction of restricted practice. During this period the most common procedures were EGDs (7.9/unit/week; 88 % for bleeding; the remainder for foreign body and feeding tube placement); ERCPs (5/unit/week; for cholangitis in 67 % and obstructive jaundice in 20 %); Colonoscopies (4/unit/week for bleeding in 77 % or colitis in 23 %) and least common were EUS (3/unit/week for tumor biopsies). Of the sites, 44 % performed pre-procedure COVID testing and the proportion of COVID-positive patients undergoing procedures was 4.6 % in the first 2 weeks and up to 19.6 % in the subsequent 2 weeks. The majority of COVID-positive patients undergoing procedures underwent EGD (30.6 % COVID +) and ERCP (10.2 % COVID +). Conclusions  COVID-19 has profoundly impacted the operation of endoscopy units in the New York region. Our data show the impact of a restricted emergency practice on endoscopy volumes and the proportion of expected COVID positive cases during the peak time of the pandemic.
PMCID:7695511
PMID: 33269322
ISSN: 2364-3722
CID: 4694312

Clinical utility of wide-area transepithelial sampling with three-dimensional computer-assisted analysis (WATS3D) in identifying Barrett's esophagus and associated neoplasia

Kaul, Vivek; Gross, Seth; Corbett, F Scott; Malik, Zubair; Smith, Michael S; Tofani, Christina; Infantolino, Anthony
Sampling error during screening and surveillance endoscopy is a well-recognized problem. Wide-area transepithelial sampling with three-dimensional computer-assisted analysis (WATS3D), used adjunctively to forceps biopsy (FB), has been shown to increase the detection of Barrett's esophagus (BE) and BE-associated neoplasia. We evaluated the clinical utility of WATS3D and its impact on the management of patients with BE and dysplasia. Between 2013 and 2018, 432 consecutive patients who had a WATS3D positive and an accompanying FB negative result were identified. Physicians were contacted to determine if the WATS3D result impacted their decision to enroll patients in surveillance or increase the frequency of surveillance, recommend ablation, and/or initiate or increase the dose of proton pump inhibitors (PPIs). WATS3D directly impacted the management of 97.8% of 317 BE patients; 96.2% were enrolled in surveillance and 60.2% were started on PPIs or their dose was increased. WATS3D impacted the management of 94.9% and 94.1% of the 98 low-grade dysplasia and 17 high-grade dysplasia patients, respectively. As a result of WATS3D, 33.7% of low-grade dysplasia and 70.6% of high-grade dysplasia patients underwent endoscopic therapy. More than 37% of all dysplasia patients were enrolled in a surveillance program, and nearly 30% were scheduled to be surveilled more frequently. PPIs were either initiated, or the dose was increased in more than 54% of all dysplasia patients. We demonstrate that WATS3D has high clinical utility. By prompting physicians to change their clinical management in patients with negative FB results, WATS3D, used adjunctively to FB, directly impacts patient management, and improves patient outcomes.
PMID: 32607543
ISSN: 1442-2050
CID: 4525032

The history of artificial intelligence in medicine

Kaul, Vivek; Enslin, Sarah; Gross, Seth A
Artificial intelligence (AI) was first described in 1950; however, several limitations in early models prevented widespread acceptance and application to medicine. In the early 2000s, many of these limitations were overcome by the advent of deep learning. Now AI systems are capable of analyzing complex algorithms and self-learning, we enter a new age in medicine where AI can be applied to clinical practice through risk assessment models, improving diagnostic accuracy and improving workflow efficiency. This article presents a brief historical perspective on the evolution of AI over the last several decades and the introduction and development of AI in medicine in recent years. A brief summary of the major applications of AI in gastroenterology and endoscopy are also presented, which will be reviewed in further detail by several other articles in this issue of GIE.
PMID: 32565184
ISSN: 1097-6779
CID: 4524862