Gastroenterology Commons^™

Use Of Methotrexate In Inflammatory Bowel Disease In 2014: A User's Guide, A. Swaminath, R. Taunk, G. Lawlor

Journal Articles

Methotrexate has been used an immunomodulator in many autoimmune diseases, including inflammatory bowel disease. However, many physicians are unfamiliar or uncomfortable with its use in the management of inflammatory bowel disease. We summarize the data for use of methotrexate in common clinical scenarios: (1) steroid dependant Crohn's disease (CD); (2) maintenance of remission in steroid free CD; (3) azathioprine failures in CD; (4) in combination therapy with Anti-TNF agents in CD; (5) decreasing antibody formation to Anti-TNF therapy in CD; (6) management of fistulizing disease in CD; and (7) as well as induction and maintenance of remission in ulcerative colitis. …

Enhanced Nicotinic Receptor Mediated Relaxations In Gastroesophageal Muscle Fibers From Barrett's Esophagus Patients, L. S. Miller, A. K. Vegesna, A. S. Braverman, M. F. Barbe, M. R. Ruggieri

Journal Articles

No abstract provided.

Ethnic Disparities In The Risk Of Colorectal Adenomas Associated With Aspirin And Statin Use: A Retrospective Multiethnic Study, A. H. Davis-Yadley, S. Lipka, H. Shen, H. Shah, S. Swarup, A. Barnowsky, J. Silpe, A. Abraham, P. Viswanathan, B. Krishnamachari, +4 Additional Authors

Journal Articles

BACKGROUND: Although data on the inverse association between colorectal adenomas (CRA) and daily aspirin or statin therapy exists in white and black patients, scarce data exists on these associations in the Hispanic population. With a rapidly increasing Hispanic population in the United States, defining the association in Hispanics is crucial. METHODS: The study sample included 1,843 consecutive patients who underwent a colonoscopy (screening or diagnostic) from 2009 to 2011 at a community hospital in East Meadow, New York. Data was then extracted from patient charts regarding aspirin and/or statin use. Adjusted odds ratios (OR) and their 95% confidence intervals (CI) …

Histological Healing Favors Lower Risk Of Colon Carcinoma In Extensive Ulcerative Colitis, B. I. Korelitz, K. Sultan, M. Kothari, L. Arapos, J. Schneider, G. Panagopoulos

Journal Articles

AIM: To search for the answer in extensive ulcerative colitis as to whether histological inflammation persisting despite endoscopic mucosal healing serves to increase the risk of colon cancer (CC) or high grade dysplasia (HGD). METHODS: This is a single center (Lenox Hill Hospital) retrospective cohort and descriptive study of extensive ulcerative colitis (UC) for 20 years or more with a minimum of 3 surveillance colonoscopies and biopsies performed after the first 10 years of UC diagnosis. Data analyzed included: duration of UC, date of diagnosis of (CC) or (HGD), number of surveillance colonoscopies, and biopsies showing histological inflammation and its …

Interobserver Agreement For Single Operator Choledochoscopy Imaging: Can We Do Better?, A. Sethi, T. Doukides, D. V. Sejpal, D. K. Pleskow, A. Slivka, D. G. Adler, R. J. Shah, S. A. Edmundowicz, T. Itoi, M. Kahaleh, +3 Additional Authors

Journal Articles

Background. The SpyGlass Direct Visualization System (Boston Scientific, Natick, MA) is routinely used during single operator choledochoscopy (SOC) to identify biliary lesions or strictures with a diagnostic accuracy up to 88%. The objective of this study was to determine the interobserver agreement (IOA) of modified scoring criteria for diagnosing biliary lesions/strictures. Methods. 27 SPY SOC video clips were reviewed and scored by 9 interventional endoscopists based on published criteria that included the presence and severity of surface structure, vasculature visualization, lesions, and findings. Results. Overall IOA was "slight" for all variables. The K statistics are as follows: surface (K = …

Nodular Lymphoid Hyperplasia In A Patient Initially Believed To Have Familial Adenomatous Polyposis, S. Altafi, A. Volfson, M. J. Mckinley

Journal Articles

No abstract provided.

Perforation In A Patient With Stercoral Colitis And Diverticulosis: Who Did It?, V. R. Bhatt, S. Murukutla, J. Dipoce, S. Gustafson, D. Sarkany, K. Mody, W. D. Widmann, A. Gottesman

Journal Articles

Stercoral colitis with perforation of the colon is an uncommon, yet life-threatening cause of the acute abdomen. No one defining symptom exists for stercoral colitis; it may present asymptomatically or with vague symptoms. Diagnostic delay may result in perforation of the colon resulting in complications, even death. Moreover, stercoral perforation of the colon can also present with localized left lower quadrant abdominal pain masquerading as diverticulitis. Diverticular diseases and stercoral colitis share similar pathophysiology; furthermore, they may coexist, further complicating the diagnostic dilemma. The ability to decide the cause of perforation in a patient with both stercoral colitis and diverticulosis …

Resident Knowledge Of Colorectal Cancer Screening Assessed By Web-Based Survey, S. Akerman, S. L. Aronson, M. A. Cerulli, M. Akerman, K. Sultan

Journal Articles

BACKGROUND: To evaluate resident knowledge of colorectal cancer (CRC) screening guidelines and to define areas requiring attention. METHODS: A survey was created using three published guidelines for CRC screening. Program directors for internal medicine residency programs were contacted within the metro New York City area to have their residents participate. RESULTS: Five programs participated, and 115 responses were recorded. For the appropriate testing and interval to screen for CRC, 61/115 residents identified flexible sigmoidoscopy every 5 years, 108/115 identified colonoscopy every 10 years, 16/115 identified double contrast barium enema (DCBE) every 5 years and only 12/115 thought CT-colography every 5 …

Appendiceal Adenocarcinoma In A Patient With Chronic Ulcerative Colitis: What Is The Appropriate Surgical Procedure?, H. F. Shen, S. Lipka, S. Katz

Journal Articles

No abstract provided.

Capsule Endoscopy In Crohn's Disease: Are We Seeing Any Better?, D. Hudesman, J. Mazurek, A. Swaminath

Journal Articles

Crohn's disease (CD) is a complex, immune-mediated disorder that often requires a multi-modality approach for optimal diagnosis and management. While traditional methods include ileocolonoscopy and radiologic modalities, increasingly, capsule endoscopy (CE) has been incorporated into the algorithm for both the diagnosis and monitoring of CD. Multiple studies have examined the utility of this emerging technology in the management of CD, and have compared it to other available modalities. CE offers a noninvasive approach to evaluate areas of the small bowel that are difficult to reach with traditional endoscopy. Furthermore, CE maybe favored in specific sub segments of patients with inflammatory …

Celiac Disease: Advances In Diagnostic Testing?, Alicia A. Hanson

Physician Assistant Scholarly Project Posters

• Celiac disease (CD) is a gluten-sensitivity enteropathy that occurs in genetically susceptible individuals upon ingestion of gluten and resolves when gluten is withdrawn from one’s diet.

• Serological markers play a major role in the diagnosis of celiac disease, however a small intestinal biopsy is currently the gold standard in symptomatic individuals.

• The purpose of this study was to determine if serological testing alone is sufficient to confirm the diagnosis of CD and therefore eliminate the need for a biopsy.

• The review of literature explored studies that compared small intestinal biopsy with different serological testing in males …

Comparing The Long Term Use Of H2 Antagonists (H2ras) And Proton Pump Inhibitors (Ppis) And The Incidence Of Colitis, Reiner Kremer

Physician Assistant Scholarly Project Posters

• Commonly used medications for GERD may affect the colonic mucosa

• H2 antagonists (H2RAs) ranitidine, cimetidine famotidine reduce acid secretion by 60 to 70%.

• Proton pump inhibitors (PPIs) omeprazole, pantoprazole, lansoprazole, esomeprazole and rabeprazole reduce acid secretion by inhibiting the H+ (proton) secreting pump, reducing hydrochloric acid by 80 to 95%.

• Diarrhea is one of the most commonly reported adverse events.

• H2RAs and PPIs have the physiological and functional potential to interfere with gastrointestinal physiology by altering intestinal pH.

• Microcytic colitis causing chronic diarrhea and colonic inflammation is a significant complication risk after the > 4-8 …

Effects Of Whole Body Therapeutic Hypothermia On Gastrointestinal Morbidity And Feeding Tolerance In Infants With Hypoxic Ischemic Encephalopathy., Kimberly M. Thornton, Hongying Dai, Seth Septer, Joshua E. Petrikin

Manuscripts, Articles, Book Chapters and Other Papers

Objective. This retrospective cohort study evaluated the effects of whole body therapeutic hypothermia (WBTH) on gastrointestinal (GI) morbidity and feeding tolerance in infants with moderate-to-severe hypoxic ischemic encephalopathy (HIE). Study Design. Infants ≥ 35 weeks gestational age and ≥1800 grams birth weight with moderate-to-severe HIE treated from 2000 to 2012 were compared. 68 patients had documented strictly defined criteria for WBTH: 32 historical control patients did not receive WBTH (non-WBTH) and 36 cohort patients received WBTH. Result. More of the non-WBTH group infants never initiated enteral feeds (28% versus 6%; P = 0.02), never reached full enteral feeds (38% versus …

Comparing Fecal Microbiota Transplant (Fmt) To Vancomycin: In Treatment Of Recurrent Clostridium Difficile Infections (Cdi), Christopher Seil

Physician Assistant Scholarly Project Posters

• Clostridium difficile infection (CDI) is the main cause of antibiotic-associated pseudomembranous colitis.

• CDI has tripled over the last ten years due to the increased use of broad spectrum antibiotics. CDI has become increasingly difficult to manage with traditional therapies such as metronidazole and vancomycin due to mutations in the pathogen, resulting in resistant organisms.

• The purpose of this review was to determine if fecal microbiota transplantation (FMT) is more effective in treating and curing CDIs than traditional vancomycin therapy.

• The hypothesis was that FMT will have better treatment outcomes than traditional vancomycin therapy.

• The findings …

A Prospective Study Of Periodontal Disease And Risk Of Gastric And Duodenal Ulcer In Male Health Professionals, Matthew R. Boylan, Hamed Khalili, Edward S. Huang, Dominique S. Michaud, Jacques Izard, Kaumudi J. Joshipura, Andrew T. Chan

Department of Food Science and Technology: Faculty Publications

Periodontal disease is characterized by microbial shifts within the oral cavity and chronic inflammation of the gingival tissue, and can lead to tooth loss. Several studies support an association between periodontal disease and risk of chronic systemic conditions, including vascular disease, chronic obstructive pulmonary disease, diabetes mellitus, and cancer, including gastric adenocarcinoma. These associations may be mediated by systemic inflammation, the immune response to periodontal infection, or direct invasion by pathogens. Previous studies of periodontal disease and risk of peptic ulcer have been limited by cross-sectional design, diagnoses that were not confirmed by medical record review, and a lack of …

Treatment Of Chronic Hepatitis D Patients With Pegylated Interferon: A Real-World Experience, Zaigham Abbas, Mohammad S. Memon, Hammad Mithani, Wasim Jafri, Saeed Hamid

Section of Gastroenterology

Background: Published experience of treating chronic hepatitis D patients with pegylated interferon (PEG-IFN)-alpha is limited. The aim of this study was to determine the efficacy of 48 weeks of treatment with PEG-IFN in naive patients outside the clinical trial setting, in the real world.

Methods: Patients with chronic hepatitis D were treated with PEG-IFN. The primary end points were sustained clearance of HDV RNA and normal alanine aminotransferase (ALT) at 24 weeks post-treatment.

Results: The total number of patients treated with PEG-IFN was 104; 91 males, mean age ±SD 30.1 ±10.0 years (range 15-55). Cirrhosis was present in …

Analysis Of The Role Of Astrocyte Elevated Gene-1 In Normal Liver Physiology And In The Onset And Progression Of Hepatocellular Carcinoma, Chadia L. Robertson

Theses and Dissertations

First identified over a decade ago, Astrocyte Elevated Gene-1 (AEG-1) has been studied extensively due to early reports of its overexpression in various cancer cell lines. Research groups all over the globe including our own have since identified AEG-1 overexpression in cancers of diverse lineages including cancers of the liver, colon, skin, prostate, breast, lung, esophagus, neurons and neuronal glia as compared to matched normal tissue. A comprehensive and convincing body of data currently points to AEG-1 as an essential component, critical to the progression and perhaps onset of cancer. AEG-1 is a potent activator of multiple pro-tumorigenic signal transduction …

Salmonella Cholecystitis: Atypical Presentation Of A Typical Condition, Rehan Ali, Shakeel Ahmed, Maqbool Qadir, Huba Atiq, Muhammad Hamid

Department of Emergency Medicine

Salmonella cholecystitis is a rare but important complication of Salmonella typhi infection. We are reporting an 11 years old female child who presented with complaints of high-grade fever, jaundice and right sided abdominal pain (Charcot's triad). Her examination showed tender hepatomegaly. Initial blood results revealed high white cell counts with left shift, deranged liver function tests. Abdominal ultrasonography revealed distended gallbladder with minimal layer of sludge seen within its lumen along with streak of pericholecystic fluid. Blood culture grew Salmonella typhi. She was successfully treated with intravenous ceftriaxone.

Job's Syndrome With An Atypical Presentation, Abbas Ali Tasneem, Sabahat Sarfaraz, Syed Mujahid Hassan, Nasir Hassan Luck, Sabiha Anis, Zaigham Abbas

Section of Gastroenterology

Hyper Immunoglobulin E syndrome also called Job's or Buckley Syndrome is a rare primary immunodeficiency disease characterized by elevated serum IgE levels (> 2000 IU/ml), recurrent infections and eosinophilia. Other features include coarse facies and non-immunologic abnormalities of the dentition, bones, vasculature and connective tissues. We are reporting a case of a twenty four years old male with coarse facies who presented with severe pallor and upper gastrointestinal bleeding. Investigations revealed markedly elevated serum IgE levels (11,800 IU/ml), severe anaemia, esophageoduodenal erosions, Helicobacter pylori (H. pylori) gastritis and oro-esophageal candidiasis.

Efficacy And Safety Of Infliximab In Older Inflammatory Bowel Disease Patients, Christina Cress Lindenmeyer, Md, Stephanie M. Moleski, Md, Maureen P. Whitsett, Med., Patricia L. Kozuch, Md

Division of Gastroenterology and Hepatology Faculty Papers

Background:

The limited data regarding treatment of inflammatory bowel disease (IBD) with anti-tumor necrosis factor antibodies in older patients suggest equal efficacy but higher morbidity and mortality compared to younger patients. This retrospective case control study aims to clarify the efficacy and safety of infliximab (IFX) in older IBD patients.

Recruitment Of Tlr Adapter Trif To Tlr4 Signaling Complex Is Mediated By The Second Helical Region Of Trif Tir Domain, Wenji Piao, Lisa W. Ru, Kurt H. Piepenbrink, Eric J. Sundberg, Stefanie N. Vogel, Vladimir Y. Toshchakov

Food for Health: Publications

Toll/IL-1R resistance (TIR) domain–containing adapter-inducing IFN-β (TRIF) is a Toll-like receptor (TLR) adapter that mediates MyD88-independent induction of type I interferons through activation of IFN regulatory factor 3 and NFκB. We have examined peptides derived from the TRIF TIR domain for ability to inhibit TLR4. In addition to a previously identified BB loop peptide (TF4), a peptide derived from putative helix B of TRIF TIR (TF5) strongly inhibits LPS-induced cytokine and MAPK activation in wild-type cells. TF5 failed to inhibit LPS-induced cytokine and kinase activation in TRIF-deficient immortalized bone-marrow–derived macrophage, but was fully inhibitory in MyD88 knockout cells. TF5 does …

Lactobacillus Acidophilus Alleviates Platelet-Activating Factor-Induced Inflammatory Responses In Human Intestinal Epithelial Cells, Alip Borthakur, Sumit Bhattacharyya, Anoop Kumar, Arivarasu Natarajan Anbazhagan, Joanne K. Tobacman, Pradeep K. Dudeja

Clinical & Translational Sciences

Probiotics have been used as alternative prevention and therapy modalities in intestinal inflammatory disorders including inflammatory bowel diseases (IBD) and necrotizing enterocolitis (NEC). Pathophysiology of IBD and NEC includes the production of diverse lipid mediators, including platelet-activating factor (PAF) that mediate inflammatory responses in the disease. PAF is known to activate NF-kB, however, the mechanisms of PAF-induced inflammation are not fully defined. We have recently described a novel PAF-triggered pathway of NF-κB activation and IL-8 production in intestinal epithelial cells (IECs), requiring the pivotal role of the adaptor protein Bcl10 and its interactions with CARMA3 and MALT1. The current studies …

Occupational Exposure To Hepatitis C Virus: Early T-Cell Responses In The Absence Of Seroconversion In A Longitudinal Cohort Study., Theo Heller, Jens Martin Werner, Fareed Rahman, Eishiro Mizukoshi, Yuji Sobao, Ann Marie Gordon, Arlene Sheets, Averell H. Sherker, Ellen Kessler, Kathleen S. Bean, Steven K. Herrine, M'Lou Stevens, James Schmitt, Barbara Rehermann

Division of Gastroenterology and Hepatology Faculty Papers

BACKGROUND: T-cell responses have been described in seronegative patients who test negative for hepatitis C virus (HCV) RNA despite frequent HCV exposure. However, the cross-sectional design of those studies did not clarify whether T cells were indeed induced by low-level HCV exposure without seroconversion or whether they resulted from regular acute infection with subsequent antibody loss.

METHODS: Over a 10-year period, our longitudinal study recruited 72 healthcare workers with documented HCV exposure. We studied viremia and antibody and T-cell responses longitudinally for 6 months.

RESULTS: All healthcare workers remained negative for HCV RNA and antibodies. However, 48% developed proliferative T-cell …

Comparison Of The Virulence Markers Of Helicobacter Pylori And Their Associated Diseases In Patients From Pakistan And Afghanistan, Javed Yakoob, Zaigham Abbas, Wasim Jafri, Muhammad W. Usman, Fatima Jafri, Safia Awan

Section of Gastroenterology

BACKGROUND/AIM: Helicobacter pylori is a Gram-negative bacteria, which is associated with development of gastroduodenal diseases. The prevalence of H. pylori and the virulence markers cytotoxin-associated gene A and E (cagA, cagE) and vacuolating-associated cytotoxin gene (vacA) alleles varies in different parts of the world. H. pylori virulence markers cagA, cagE, and vacA alleles in local and Afghan nationals with H. pylori-associated gastroduodenal diseases were studied.

PATIENTS AND METHODS:Two hundred and ten patients with upper gastrointestinal symptoms and positive for H. pylori by the urease test and histology were included. One hundred and nineteen were local nationals and 91 were Afghans. …

Sessile Serrated Adenomas In The Proximal Colon Are Likely To Be Flat, Large And Occur In Smokers, Tarun Rustagi, Priya Rangasamy, Matthew Myers, Melinda Sanders, Haleh Vaziri, George Y. Wu, John W. Birk, Petr Protiva, Joseph C. Anderson

Dartmouth Scholarship

Aim: To examine the epidemiology and the morphology of the proximal sessile serrated adenomas (SSAs).

Methods: We conducted a retrospective study to identify patients with SSAs using a university-based hospital pathology database query from January 2007 to April 2011. Data collected included: age, gender, ethnicity, body mass index, diabetes, smoking, family history of colorectal cancer, aspirin, and statin use. We collected data on morphology of SSAs including site (proximal or distal), size, and endoscopic appearance (flat or protuberant). We also compared proximal SSAs to proximal tubular adenomas detected during same time period.

A Multicenter, Prospective, Randomized Comparison Of A Novel Signal Transmission Capsule Endoscope To An Existing Capsule Endoscope., Eric H Choi, Klaus Mergener, Carol Semrad, Laurel Fisher, David R Cave, Milan Dodig, Carol Burke, Jonathan A Leighton, David Kastenberg, Peter Simpson, James Sul, Kanishka Bhattacharya, Roger Charles, Lauren Gerson, Luke Weber, Glenn Eisen, Warren Reidel, John J Vargo, Jamile Wakim-Fleming, Simon K Lo

Division of Gastroenterology and Hepatology Faculty Papers

BACKGROUND: MiroCam, a capsule endoscope, uses a novel transmission technology, electric-field propagation, which uses the human body as a conduction medium for data transmission.

OBJECTIVE: To compare the ability of the MiroCam (MC) and PillCam (PC) to identify sources of obscure GI bleeding (OGIB).

DESIGN: Prospective, multicenter, comparative study.

SETTING: Six academic hospitals.

PATIENTS: A total of 105 patients with OGIB.

INTERVENTION: Patients ingested both the MC and PC capsules sequentially in a randomized fashion.

MAIN OUTCOME MEASUREMENTS: Concordance of rates in identifying a source of OGIB, operational times, and rates of complete small-bowel examination.

RESULTS: Data analysis resulted in …

Wilson's Disease: Experience At A Tertiary Care Hospital., Om Parkash, Adil Ayub, Wasim Jafri, Syed H Shah, Saeed Hamid

Department of Medicine

Wilson's disease (WD) is a rare autosomal recessive disorder of copper metabolism. Data regarding WD is not available from Pakistan. A cross-sectional study was conducted at The Aga Khan University Hospital, Karachi, and all patients admitted with primary and secondary diagnosis of Wilson's disease were added. A total of 47 patients were seen; 68% (n = 32) were male. The mean age was 26.6 ± 9.97 years. Most of the patients presented with hepatic, (n = 22, 46.8%), neurological, (n = 17, 36.2%) and psychiatric (n = 8, 17%) symptoms. Mean ceruloplasmin level was 0.17 ± 0.13 g/dl; it was < 0.25 g/dl in 39 (86.6%) patients. Serum copper (Cu) was reduced in 32 (68.1%) patients and 24-hr-urinary Cu was raised in 22 (47.6%) patients. Slit lamp examination for Kayser-Fleischer (KF) rings was done on 15 (31.9%) patients and 9 (60%) of them had KF rings. Mean serum aspartate transaminase (AST) / alanine transaminases (ALT) ratio was 1.92 and median alkaline phosphatase / total bilirubin ratio was 79.30 (IQR 35.05; 166.50).

Varied Presentation Of Celiac Disease In Pakistani Adults, Zaigham Abbas, Sajjad Raza, Javed Yakoob, Shahab Abid, Saeed Hamid, Hasnain Shah, Wasim Jafri

Section of Gastroenterology

he objective of this retrospective study was to evaluate presentation of celiac disease in adults. It included 77 patients, 41 (53.2%) males with median age 26 years and median body mass index of 18 (16 â�� 22) kg/m2. Typical presentation with gastrointestinal symptoms was seen in 76.6%. Atypical presentation with extra intestinal complaints in 7.8% and silent presentation in 15.6%. Major symptoms were diarrhea in 64.9%, weight loss 36.4%, abdominal pain 35.1%, vomiting 32.5%, pallor 24.7%, and weakness 13%. Iron deficiency was documented in 20.8%, B12 deficiency in 9.1%, folic acid deficiency in 6.5% and vitamin D deficiency in 10.4%. …

Is Laparoscopy A Risk Factor For Bile Duct Injury During Cholecystectomy?, Terrence M. Fullum, Stephanie R. Downing, Gezzer Ortega, David C. Chang, Tolulope A. Oyetunji, Kendra Van Kirk, Daniel D. Tran, Ian Woods, Edward E. Cornwell, Patricia L. Turner

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND AND OBJECTIVES: Previously, risk factors for bile duct injury have been identified as acute cholecystitis, male gender, older age, aberrant biliary anatomy, and laparoscopic cholecystectomy.

METHODS: A retrospective analysis of the Nationwide Inpatient Sample from 1998 to 2006 was performed with an inclusion criterion of cholecystectomy performed on hospital day 0 or 1. Patient- and hospital-level factors potentially associated with bile duct injury were examined by logistic regression.

RESULTS: A total of 377,424 cholecystectomy patients were identified. There were 1124 bile duct injuries (0.30%), with 177 (0.06%) in the laparoscopic cholecystectomy group and 947 (1.46%) in the open cholecystectomy …

Methods For Quantifying T Cell Receptor Binding Affinities And Thermodynamics, Kurt H. Piepenbrink, Brian E. Gloor, Kathryn M. Armstrong, Brian M. Baker

Food for Health: Publications

αβ T cell receptors (TCRs) recognize peptide antigens bound and presented by class I or class II major histocompatibility complex (MHC) proteins. Recognition of a peptide/MHC complex is required for initiation and propagation of a cellular immune response, as well as the development and maintenance of the T cell repertoire. Here we discuss methods to quantify the affinities and thermodynamics of interactions between soluble ectodomains of TCRs and their peptide/MHC ligands, focusing on titration calorimetry, surface plasmon resonance, and fluorescence anisotropy. As TCRs typically bind ligand with weak-to-moderate affinities, we focus the discussion on means to enhance the accuracy and …